Synthesis of New Biologically active 4-isobutylhydrotropoyl Derivatives

 

Dr. T.M. Ibrahim1*, and Mohamed H.Y. Kreet2

1Chemistry Department, Faculty of Science, Al Azhar University, Nasr City, Egypt

2Department of Toxic and Narcotic drug, Forensic Medicine,  Cairo, Egypt

*Corresponding Author E-mail:

 

ABSTRACT:

The synthesis of 4-isobutylhydrotropoylamino acids (12-17), dipeptide methyl ester (18-71), dipeptide (72-125) and their corresponding hydrazides (126-179) is described .All the synthesized compounds were found to be active against some of the tested micro organisms and fungi.

 

KEYWORDS:

 

1. INTRODUCTION:

Recently the synthesis of many substituted nitro, amino and halophthaloylamino acid and peptide Derivatives was reported(1-4) . All these compounds were found  to   possess  specific  antimicrobial activity(1-4). This promoted me to synthesis some 4-isobutylhydrotropoylamino acids, dipeptide methyl ester, dipeptide and hydrazides.

 

EXPERIMENTAL:

Melting points are uncorrected and determined using electrothermal melting point apparatus "SMPI". Purity of compounds was checked by Thin layer chromatography "TLC" on plastic sheets silica gel-60- "Merck" and developed with benzene-ethyl acetate (3:1) using  iodine-KI (20%)solution as spraying  agent. Benzidine, ninhydrin, hydroxamate, and silver nitrate tests were used for detection reactions. The infrared "IR" Spectra were taken in KBr on   Perkin Elmer IR 5300 spectrometer. UV and visible spectra were measured on Shimadzu UV160  spectrometer. The mass spectra  were taken  on GC MS-QP 1000  mass spectrometer at 70 ev. Elemental analysies were carried out in microanalytical Research Center, Faculty of Science, Cairo University. Optical rotationswere measured in Bellingham-Stanley  polarimeter with 1 dm tube, C=5 in DMF.

 

Biological activities were measured in Botany and Microbiology department.

 

General procedure for synthesis of 4-isobutylhydrotropoylamino Acid derivatives  (12-17):

The amino acid (0.001 mole) was dissolved in 1N-NaOH, and the solution cooled to (10 °C) (solution A). 4-isobutylhydrotropoyl acid chloride (11) [0.01mole] was dissolved in benzene (solution B). Solution (A) was gradually added during 75 mins. with stirring to solution (B). The temperature of the reaction mixture was kept at (10 °C) until complete addition, and the reaction mixture stirred for further three hrs. at room temperature. The benzene layer was separated out, and the aqueous layer acidified with 2N-HCl to pH =5. The crude compound (12-17) was filtered, washed with cold water and recrystallized from –water.

 

The IR spectrum of compounds (12-17) in KBr showed a characteristic bands at: 3379, 3272 cm-1 (NH); 3092 cm-1 (CH-aromatic), 2955, 2872 cm-1 (CH3-valine); 1717cm-1  (C=O)and another bands characteristic for the remaining part of the  molecule. 1Hn.m.r spectrum of compounds(12-17)  in dimethyl sulfoxide-d6 exhibited the following signals at δ : 0.8 (s, 6H,  2CH3-alanine); 1.808 (m, 6H, CH(CH3)2- alanine ); 3.6 (m, 1H, CH valine), 7.08-7.199 (m, isobutylhydrotropoyl protons), 8.14,8.13 (d, 1H,NH), 12.19 (b, 1H, OH-carboxylic), which confirmed its structure.

 

General procedure for synthesisof 4- isobutylhydrotropoyldipeptide methyl esters (18-71): 

4-isobutyl-hydrotropoyl amino acid  (12-17); 0.001 mole) was dissolved in (15 ml.) tetrahydrofuran (THF) [Solution A]. Amino acid methyl ester hydrochloride (1-9; 0.001mole) was suspended in (THF; 20 ml.) containing triethylamine (0.5 ml.). The mixture was stirred for 30 min; then cooled to (0°C). The precipitated triethylamine hydrochloride was filtered off {the filtrate contains free amino acid methyl ester [Solution B]}.   Solution (A) was added to solution (B), and the mixture cooled to 0 °C, then N,N`-dicyclohexylcarbodiamide [DCC; 0,206 g; 0.001 mole] was added. The reaction mixture was stirred for 4-6 hrs. at (0°C), and left over night. The precipitated dicyclohexylurea (DCC) was filtered off. The filtrate evaporated in vacuum and the residual material was purified by recrystallization from ethanol-water to give compounds   (18-71).

 

The synthesized compounds (18-71) were chromato graphically homogeneous when developed with benzidine, iodine solution, and gave positive hydroxamate reaction and negative ninhydrin test. The IR spectrum of compounds (18-71) in KBr showed  the characteristic bands at: 3325, 3296 cm-1 (NH, CONH); 2928,2856 cm-1   (CH3); 1657cm-1 (C=O); 1601 cm-1 (COOCH3); and other frequencies for the remaining part of the molecule which confirmed its structure. 1Hn.m.r spectrum of compounds (18-71) in dimethylsulfoxide-d6 exhibited the following signals at δ : 1.02 (s,6H, 2CH3-Methionine); 1.52(m,1H,CH-serine); 2.5(s, 2H,  CH2 methionine -); 3.2 (d, 1H, CH-CH serine); 3.8(s, 1H,  CH- methionine); 7.26_7.75 (m, aromatic protons),   8.34, 8.35 (d, 1H,NH-serine), 11.26 (b, 1H, OH-carboxylic) which confirmed its structure.

 

General procedure for synthesis of 4-isobutylhydrotropoyldipeptides (72-125)

4-isobutylhydrotropoyldipeptide methyl ester (18-71); 0.001mole) was added to a solution of 0.5-N NaOH.  The mixture was refluxed with continuous stirring for 1 hour at (100 °C) on water bath. The reaction mixture was allowed to cool, then acidified with 1N-HCl to pH=5. The crude product (72-125) was separated, filtered and purified by recrystallization from DMF.

 

All the synthesized compounds (72-125) were chromato-graphically homogeneous when developed with iodine solution, benzidine and gave negative ninhydrin test, and hydroxmate reaction. The IR spectrum of compounds (72-125) in KBr showed the characteristic bands at: 3394, 3055cm-1 (NH, CONH); 2925, 2871 cm-1   (CH- aliphatic); 1718 cm-1 (C=O); and other frequencies for the remaining part of the molecule which confirmed its structure. 1HN.M.R spectrum of compounds (72-125) in dimethylsulfoxide-d6 exhibited the following signals at δ : 2.2(s, 2H, CH2-glycine); 3.3 (s, 2H, CH2-glycine);  7.1-7,3 (m, aromatic protons), 12.19 (s, 1H, OH-carboxilic) which confirmed its structure.

 

General procedure for synthesis of 4-isobutyl-hydrotropoyl dipeptide hydrazides (126-179):

4-isobutylhydrotropoyl dipeptide methyl ester (18-71; 0.001mole) was dissolved in (30 ml) of 1M alcoholic hydrazine hydrate (prepared from 6.6 ml hydrazine hydrate in 93.4 ml of abs. ethanol). The reaction mixture was heated on water bath for ½ hr. and kept 24 hrs in the refrigerator. The hydrazide was separated out and recrystallized from ethanol-water.

 

All compounds (126-179) were chromatographically homogenous when developed with iodine solution, benzidine, and gave positive silver nitrate test and negative hydroxamate, and ninhydrin tests.

 

The IR spectrum of compounds (126-179) in KBr showed the characteristic bands at: 3580, 3099 cm-1 (NH, NH2); 2871, 2756 cm-1   (CH- aliphatic); 1619, 1588 cm-1 (amide I, amide II) and other frequencies for the remaining part of the molecule which confirmed its structure. 1Hn.m.r spectrum of compounds (126-179)  in dimethylsulfoxide-d6 exhibited the following signals at δ : 2.49 (m, 1H,  CH-alanine);   3.3 (s,2H,CH2-Leucine);  3.6 (s, 3H, COOCH3); 3.8 (t,2H,CH2-alanine); 5.51,5.54 (d, 1H,NH- Leucine); 7.04-7.18 (m, aromatic protons), 8.2 (d, 1H,NH-alanine), 8.24 (1H, NH Leucine) which confirmed its structure.

 

Compd. No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

18

Gly-Gly-OMe

80

108-10

0.27

-

C18H26N2O4

64.76

7.78

8.38

 

 

 

 

 

 

(334)

64.80

7.82

9.49

19

GLy-β-Ala-OMe

75

113-15

0.74

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.66

8.10

8.10

20

GLy-DL-Ala-OMe

53

110-12

0.80

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.66

8.10

8.10

21

GLy- L-Val-OMe

65

118-20

0.71

158+

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.58

7.50

22

Gly-DL-Val-OMe

70

115-17

0.75

-

C18H28N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.58

7.50

23

Gly-DL-Leu-OMe

80

125-27

O.70

-

C22H34N2O4

(390)

67.69

67.75

8.71

8.75

7.17

7.25

24

GLy-DL-Phe-OMe

60

135-37

0.58

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.83

7.62

6.65

25

GLy-DL-Ser-OMe

55

136-38

0.75

-

C19H28N2O4

62.63

7.69

7.69

 

 

 

 

 

 

(364)

62.70

7.74

7.75

26

GLy-DL-Met-OMe

63

126-28

0.66

-

C21H32N2O4S

61.76

7.65

6.86

 

 

 

 

 

 

(408)

61.78

7.68

6.99

 

 

Compd.

No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

27

β-Ala-GLy-OMe

   80

139-41

0.50

-

C19H28N2O4

65..51

8.04

8.04

 

 

 

 

 

 

(348)

65.58

8.10

8.10

28

β-Ala- β -ALa-OMe

   80

140-42

0.75

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.32

7.85

29

β -Ala- DL-ALa-OMe

80

136-38

0.59

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.32

7.85

30

β- Ala -L-Val -OMe

52

128-30

0.50

210+

C22H34N2O4

62.68

6.46

6.96

 

 

 

 

 

 

(390)

62.79

6.58

7.10

31

β -Ala- DL-Val -OMe

74

212-14

0.93

-

C22H34N2O4

62.68

6.46

6.96

 

 

 

 

 

 

(390)

62.79

6.58

7.10

32

β -Ala-DL-Leu -OMe

60

152-54

0.95

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.95

6.99

33

β-Ala-DL-Phe -OMe

83

156-58

0.82

-

C26H34N2O4

71.23

7.93

6.39

 

 

 

 

 

 

(438)

71.30

8.00

6.45

34

β-Ala-DL-Ser -OMe

65

148-50

0.67

-

C20H30N2O5

66.66

7.93

7.40

 

 

 

 

 

 

(378)

63.49

7.99

7.45

35

β-Ala-DL-Met -OMe

55

160-62

0.70

-

C22H34N2O4S

62.55

8.05

6.63

 

 

 

 

 

 

(422)

62.60

8.10

6.70

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

36

DL-Val-Gly-OMe

80

149-51

0.82

-

C21H32N2O4

67. 02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.60

7.50

37

DL-Val-β-Ala-OMe

85

155-57

0.56

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.75

7.25

38

DL-Val-DL- Ala-OMe

70

150-52

0.94

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.75

7.25

39

DL-Val-L-Val-OMe

68

125-27

0.50

215+

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

40

DL-Val-DL-Val-OMe

72

129-31

0.92

-

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

41

DL-Val-DL-Leu-OMe

80

134-36

.800

-

C25H40N2O4

69.44

9.25

6.48

 

 

 

 

 

 

(432)

69.50

9.30

6.54

42

DL-Val-DL-Phe-OMe

75

128-30

0.36

-

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

43

DL-Val-DL-Ser-OMe

72

132-34

0.93

-

C22H34N2O4

65.02

6.89

6.89

 

 

 

 

 

 

(406)

65.10

6.95

6.95

44

DL-Val-DL-Met-OMe

82

154-56

0.87

-

C24H38N2O4

64.0

8.44

6.22

 

 

 

 

 

 

(450)

64.10

8.49

6.28

 

Compd.

No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

45

DL-Leu-Gly-OMe

75

160-62

0.75

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.75

7.25

46

DL-Leu- β –Ala-OMe

80

158-60

0.66

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

6.99

47

DL-Leu-DL-Ala-OMe

7075

166-68

0.84

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

6.99

48

DL-Leu L-Val-OMe

60

142-44

0.60

310+

C25H40N2O4

69.44

9..25

6.48

 

 

 

 

 

 

(432)

69.50

9.30

6.55

49

DL-Leu-DL-Val-OMe

75

154-56

0.82

-

C25H40N2O4

69.44

9..25

6.48

 

 

 

 

 

 

(432)

69.50

9.30

6.55

50

DL-Leu-DL-Leu-OMe

82

148-50

0.46

-

C26H39N2O4

70.42

8.80

6.48

 

 

 

 

 

 

(443)

70.48

8.85

6.54

51

DL-Leu-DL-Phe-OMe

68

160-62

083

-

C29H40N2O4

72.50

8.33

5.83

 

 

 

 

 

 

(480)

72.55

8.40

5.90

52

DL-Leu-DL-Ser-OMe

74

195-97

0.92

-

C23H35N2O4

65.87

8.35

5.83

 

 

 

 

 

 

(419)

65.93

8.40

5.90

53

DL-Leu-DL-Met-OMe

65

180-82

0.78

-

C25H40N2O4S

64.65

8.62

6.03

 

 

 

 

 

 

(464)

64.70

8.67

6.09

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

54

DL-Phe-Gly -OMe

58

157-59

0.65

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.85

7.60

6.65

55

DL-Phe-β-Ala -OMe

70

158-60

0.70

-

C26H34N2O4

71.23

7.76

6.39

 

 

 

 

 

 

(438)

71.30

7.80

6.45

56

DL-Phe-DL-Ala -OMe

75

160-62

0.64

-

C26H34N2O4

71.23

7.76

6.39

 

 

 

 

 

 

(438)

71.30

7.80

6.45

57

DL-Phe-L-Val -OMe

68

175-77

0.65

250+

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

58

DL-Phe-DL_Val -OMe

84

175-77

0.85

-

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

59

DL-Phe-DL-Leu -OMe

65

190-92

0.90

-

C29H40N2O4

72.50

8.33

5.83

 

 

 

 

 

 

(480)

72.55

8.40

5.90

60

DL-Phe-DL-Phe -OMe

90

204-06

0.75

-

C32H38N2O4

74.70

7.39

5.44

 

 

 

 

 

 

(514)

74.75

5.75

549

61

DL-Phe-DL-Ser -OMe

68

212-14

0.72

-

C26H34N2O4

68.72

7.48

6.16

 

 

 

 

 

 

(454)

68.75

7.54

6.22

62

DL-Phe-DL-Met- OMe

58

213-15

0.65

-

C28H38N2O4S

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.08

 

Compd.No.

X

Yield%

M.P.C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

63

DL-Met-Gly-OMe

48

162-64

0.40

-

C21H32N2O4S

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.80

7.94

6.94

64

DL-Met -β-Ala-OMe

67

147-49

0.65

-

C22H34N2O4S

60.00

5.55

6.63

 

 

 

 

 

 

(422)

62.55

8.05

6.68

65

DL-Met-DL-Ala-OMe

70

149-51

0.49

-

C22H34N2O4S

60.00

5.55

6.63

 

 

 

 

 

 

(422)

62.55

8.05

6.68

66

DL-Met-L-Val-OMe

42

201-03

0.40

280+

C24H38N2O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.05

8.50

6.30

67

DL-Met-DL-Val-OMe

64

203-05

0.83

-

C24H38N2O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.05

8.50

6.30

68

DL-Met-DL-Leu-OMe

50

137-39

0.85

-

C25H40N2O4S1

64.65

8.62

6.03

 

 

 

 

 

 

(464)

63.55

8.68

6.10

69

DL-Met-DL-Phe-OMe

73

223-25

0.72

-

C28H38N2O4S

67.46

7.63

5.62

 

 

 

 

 

 

(498)

67.55

7.70

5.70

70

DL-Met-DL-Ser-OMe

55

202-04

0.57

-

C22H34N2O5S

60.27

7.76

6.39

 

 

 

 

 

 

(438)

60.35

7.80

6.45

71

DL-Met-Met -OMe

45

222-24

0.60

-

C24H38N2O4S

59.75

7.88

5.80

 

 

 

 

 

 

(482)

59.85

7.94

5.95

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

72

Gly-Gly

65

156-58

0.59

-

C17H24N2O4

63.75

7.50

8.75

 

 

 

 

 

 

(320)

63.80

7.55

8.80

73

GLy-β-Ala

80

163-65

0.84

-

C18H26N2O4

64.67

7.78

8.38

 

 

 

 

 

 

(334)

64.75

7.85

8.45

74

GLy-DL-Ala

85

162-64

0.68

-

C18H26N2O4

64.67

7.78

8.38

 

 

 

 

 

 

(334)

64.75

7.85

8.45

75

GLy- L-Val

68

174-76

0.50

160+

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.35

7.80

76

GLy-DL-Val

78

175-77

0.84

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.35

7.80

77

Gly-DL-Leu

65

140-42

0.86

-

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

76.10

8.59

7.50

78

GLy-DL-Phe

85

182-84

0.73

-

C24H30N2O4

70.24

7.31

6.82

 

 

 

 

 

 

(410)

70.30

7.38

6.90

79

GLy-DL-Ser

70

176-78

0.76

-

C18H26N2O4

61.71

7.42

8.00

 

 

 

 

 

 

(350)

61.79

7.49

8.07

80

GLy-DL-Met

60

195-97

0.79

-

C20H30N2O4

60.91

7.61

7.10

 

 

 

 

 

 

(394)

60.96

7.69

7.15

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

81

β-Ala-GLy

53

164-66

0.55

-

C18H26N2O4

64.67

7.78

8.38

 

 

 

 

 

 

(334)

64.73

7.83

8.43

82

β-Ala- β -ALa

72

192-95

0.65

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.56

8.10

8.10

83

β -Ala- DL-ALa

75

194-96

0.54

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.56

8.10

8.10

84

β- Ala- L-Val

47

215-17

0.55

+340

C21H32N2O4

67.02

8.51

6.96

 

 

 

 

 

 

(376)

67.10

8.60

7.44

85

β -Ala- DL-Val

69

212-14

0.80

-

C21H32N2O4

67.02

8.51

6.96

 

 

 

 

 

 

(376)

67.10

8.60

7.44

86

β -Ala-DL-Leu

55

149-51

0.85

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.76

7.20

87

β-Ala-DL-Phe

78

221-23

0.60

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.81

7.60

6.68

88

β-Ala-DL-Ser

60

154-56

0.67

-

C19H28N2O5

62.63

7.69

7.69

 

 

 

 

 

 

(364)

62.68

7.75

7.76

89

β-Ala-DL-Met

53

184-86

0.50

-

C21H32N2O4

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.85

7.90

6.90

 

Compd.No.

X

Yield%

M.P.C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

90

DL-Val-Gly

73

158-60

0.75

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.35

7.88

91

DL-Val-β-Ala

76

222-24

0.60

-

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.60

7.50

92

DL-Val-DL- Ala

48

215-17

0.52

-

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.60

7.50

93

DL-Val-L-Val

70

135-37

0.93

+230

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

7.10

94

DL-Val-DL-Val

60

134-36

0.94

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

7.10

95

DL-Val-DL-Leu

79

138-40

0.83

-

C24H38N2O4

68.89

9.09

6.93

 

 

 

 

 

 

(418)

68.95

9.15

7.10

96

DL-Val-DL-Phe

61

155-57

0.78

-

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452)

71.75

8.05

6.25

97

DL-Val-DL-Ser

51

200-02

0.72

-

C21H32N2O5

64.28

8.16

7.14

 

 

 

 

 

 

(392)

64.35

8.22

7.20

98

DL-Val-DL-Met

54

203-05

0.54

-

C23H36N2O4S

63.30

8.25

6.42

 

 

 

 

 

 

(436)

63.38

8.34

6.48

 

Compd.

No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

99

DL-Leu-Gly

85

160-62

0.70

-

C21H32N2O4

67.02

8.71

7.44

 

 

 

 

 

 

(376)

67.08

8.79

7.55

100

DL-Leu- β –Ala

89

178-80

0.54

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.80

7.25

101

DL-Leu-DL-Ala

50

180-82

0.45

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.80

7.25

102

DL-Leu L-Val

70

146-48

0.88

+180

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

103

DL-Leu-DL-Val

54

148-50

0.90

-

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

104

DL-Leu-DL-Leu

76

157-59

0.77

-

C25H37N2O4

69.93

8.62

6.52

 

 

 

 

 

 

(429)

69.99

8.69

6.62

105

DL-Leu-DL-Phe

60

207-09

0.62

-

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

106

DL-Leu-DL-Ser

53

200-02

0.65

-

C22H33N2O4

65.18

8.14

6.91

 

 

 

 

 

 

(405)

65.25

8.20

7.03

107

DL-Leu-DL-Met

70

201-03

0.76

-

C24H38N4O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.05

8.50

6.28

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

108

DL-Phe-Gly

65

145-47

0.77

-

C24H30N2O4

70.24

7.31

6.82

 

 

 

 

 

 

(410)

70.30

7.38

6.88

109

DL-Phe-β-Ala

75

165-67

0.61

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.80

7.60

6.66

110

DL-Phe-DL-Ala

80

168-70

048

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.80

7.60

6.66

111

DL-Phe-L-Val

85

180-82

0.90

+270

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452)

71.75

7.99

6.25

112

DL-Phe-DL_Val

65

180-82

0.51

-

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452)

71.75

7.99

6.25

113

DL-Phe-DL-Leu

75

210-12

0.31

-

C28H38N2O4

72.10

5.55

15.55

 

 

 

 

 

 

(466)

72.15

8.15

6.00

114

DL-Phe-DL-Phe

75

212-14

0.31

-

C31H36N2O4

74.40

7.20

5.60

 

 

 

 

 

 

(500)

74.50

7.30

5.65

115

DL-Phe-DL-Ser

70

205-07

0.42

-

C25H32N2O5

74.40

7.27

6.36

 

 

 

 

 

 

(440)

74.45

7.32

6.40

116

DL-Phe-DL-Met

73

220-22

0.66

-

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452­)

71.75

8.01

6.25

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

117

DL-Met-Gly

73

182-84

0.71

-

C20H30N2O4S

61.91

7.61

7.10

 

 

 

 

 

 

(394)

61.99

7.66

7.15

118

DL-Met -β-Ala

67

215-17

0.71

-

C21H32N2O4S

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.80

7.90

6.90

119

DL-Met-DL-Ala

77

229-31

0.55

-

C21H32N2O4S

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.80

7.90

6.90

120

DL-Met-L-Val

82

217-19

0.42

+160

C23H36N2O4S

63.30

8.25

6.42

 

 

 

 

 

 

(436)

63.35

8.30

6.50

121

DL-Met-DL-Val

87

224-26

0.84

-

C23H36N2O4S

63.30

8.25

6.42

 

 

 

 

 

 

(436)

63.35

8.30

6.50

122

DL-Met-DL-Leu

67

229-31

0.45

-

C24H38N2O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.08

8.50

6.28

123

DL-Met-DL-Phe

57

218-20

0.44

-

C27H36N2O4S

66.94

7.43

5.78

 

 

 

 

 

 

(484)

66.99

7.48

5.83

124

DL-Met-DL-Ser

77

226-28

0.45

-

C21H32N2O5S

59.43

7.54

6.60

 

 

 

 

 

 

(424)

59.48

7.60

6.65

125

DL-Met–DL-Met

72

205-07

0.56

-

C23H36N2O4S2

58.97

7.69

5.98

 

 

 

 

 

 

(468)

58.99

7.75

6.09

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

126

Gly-Gly-N2H3

80

182-84

0.60

-

C17H26N4O3

61.07

7.78

16.76

 

 

 

 

 

 

(334)

61.15

7.85

16.80

127

GLy-β-Ala-N2H3

74

215-17

0.60

-

C18H28N4O3

62.06

8.04

16.09

 

 

 

 

 

 

(348)

62.10

8.10

16.15

128

GLy-DL-Ala-N2H3

76

219-21

0.55

-

C18H28N4O3

62.06

8.04

16.09

 

 

 

 

 

 

(348)

62.10

8.10

16.15

129

GLy- L-Val-N2H3

81

217-19

0.54

+320

C20H32N4O3

63.82

8.51

14.89

 

 

 

 

 

 

(376)

63.89

8.59

14.95

130

GLy-DL-Val-N2H3

80

219-21

0.83

-

C20H32N4O3

63.82

8.51

14.89

 

 

 

 

 

 

(376)

63.89

8.59

14.95

131

Gly-DL-Leu-N2H3

55

229-31

0.54

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.68

8.75

14.40

132

GLy-DL-Phe-N2H3

54

215-17

0.35

-

C24H32N4O3

67.92

7.69

13.20

 

 

 

 

 

 

(424)

67.99

7.75

13.30

133

GLy-DL-Ser-N2H3

50

222-24

0.40

-

C18H28N4O5

59.34

7.69

15.38

 

 

 

 

 

 

(364)

59.40

7.76

15.45

134

GLy-DL-Met-N2H3

79

208-10

0.48

-

C20H32N4O3S

58.82

7.84

13.72

 

 

 

 

 

 

(408)

58.94

7.93

13.78

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

135

β –Ala-Gly-N2H3

64

186-88

0.61

-

C18H28N4O3

62.06

8.04

16.09

 

 

 

 

 

 

(348)

62.10

8.10

16.15

136

β-Ala- β -ALa-N2H3

58

227-29

0.61

-

C19H30N4O3

62.98

8.28

15.46

 

 

 

 

 

 

(362)

62.99

8.35

15.55

137

β –Ala- DL-ALa-N2H3

68

228-30

0.45

-

C19H30N4O3

62.98

8.28

15.46

 

 

 

 

 

 

(362)

62.99

8.35

15.55

138

β- Ala- L-Val -N2H3

63

226-28

0.32

+250

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.70

8.80

14.40

139

β –Ala -DL-Val -N2H3

68

224-26

0.74

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.70

8.80

14.40

140

β -Ala-DL-Leu -N2H3

58

229-31

0.35

-

C22H36N4O4

65.34

8.91

13.86

 

 

 

 

 

 

(404)

65.40

9.99

13.90

141

β-Ala-DL-Phe -N2H3

48

218-20

0.35

-

C25H34N4O3

68.49

7.76

12.78

 

 

 

 

 

 

(438)

68.55

7.80

12.83

142

β-Ala-DL-Ser -N2H3

67

226-28

0.55

-

C19H30N4O4

60.31

7.93

14.81

 

 

 

 

 

 

(378)

60.38

7.99

14.89

143

β-Ala-DL-Met -N2H3

63

205-07

0.66

-

C21H34N4O3S

59.71

8.05

13.27

 

 

 

 

 

 

(422)

59.86

8.14

13.35

 

Compd.No.

X

Yield%

M.P.C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

144

DL-Val-Gly-N2H3

56

190-92

0.61

-

C20H32N4O3

63.82

8.51

14.89

 

 

 

 

 

 

(376)

63.88

8.60

14.95

145

DL-Val-β-Ala-N2H3

50

219-21

0.72

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(391)

64.70

8.78

14.40

146

DL-Val-DL- Ala-N2H3

60

221-23

0.60

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(391)

64.70

8.78

14.40

147

DL-Val-L-Val-N2H3

65

227-29

0.42

+180

C23H38N4O3

66.02

9.09

13.39

 

 

 

 

 

 

(418)

66.10

9.15

13.45

148

DL-Val-DL-Val-N2H3

70

229-31

0.80

-

C23H38N4O3

66.02

9.09

13.39

 

 

 

 

 

 

(418)

66.10

9.15

13.45

149

DL-Val-DL-Leu-N2H3

50

233-35

0.63

-

C24H40N4O3

66.66

9.25

12.96

 

 

 

 

 

 

(432)

66.70

9.30

13.05

150

DL-Val-DL-Phe-N2H3

40

228-30

0.35

-

C27H38N4O3

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.58

8.20

12.10

151

DL-Val-DL-Ser-N2H3

60

235-37

0.42

-

C21H34N4O4

62.06

8.37

13.29

 

 

 

 

 

 

(406)

62.15

8.45

13.35

152

DL-Val-DL-Meth-N2H3

55

213-15

0.33

-

C23H38N4O3S

61.33

8.44

12.44

 

 

 

 

 

 

(450)

61.38

8.50

12.50

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

153

DL-Leu-Gly-N2H3

64

194-96

0.70

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.70

8.80

14.40

154

DL-Leu- β –Ala-N2H3

50

210-12

0.72

-

C22H36N4O3

65.34

8.91

13.86

 

 

 

 

 

 

(404)

65.40

8.99

13.95

155

DL-Leu-DL-Ala-N2H3

55

213-15

0.54

-

C22H36N4O3

65.34

8.91

13.86

 

 

 

 

 

 

(404)

65.40

8.99

13.95

156

DL-Leu L-Val-N2H3

65

221-23

0.41

+218

C24H40N4O3

66.66

9.25

12.96

 

 

 

 

 

 

(432)

66.70

9.35

13.05

157

DL-Leu-DL-Val-N2H3

73

224-26

0.84

-

C24H40N4O3

66.66

9.25

12.96

 

 

 

 

 

 

(432)

66.70

9.35

13.05

158

DL-Leu-DL-Leu-N2H3

54

235-37

0.44

-

C25H39N4O3

67.72

8.80

12.64

 

 

 

 

 

 

(443)

67.79

8.89

12.70

159

DL-Leu-DL-Phe-N2H3

45

240-42

0.43

-

C28H40N4O3

70.00

8.33

11.66

 

 

 

 

 

 

(480)

70.05

8.40

11.70

160

DL-Leu-DL-Ser-N2H3

65

238-40

0.24

-

C22H35N4O4

63.00

8.35

13.36

 

 

 

 

 

 

(419)

63.10

8.43

13.45

161

DL-Leu-DL-Met- N2H3

58

219-21

0.35

-

C24H40N4O3S

62.06

8.62

12.06

 

 

 

 

 

 

(464

62.10

8.70

12.10

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

162

DL-Phe-Gly -N2H3

43

195-97

0.48

-

C24H32N4O3

67.92

7.54

13.20

 

 

 

 

 

 

(424)

67.99

7.60

13.28

163

DL-Phe-β-Ala -N2H3

37

226-28

0.48

-

C25H34N4O3

68.49

7.76

12.78

 

 

 

 

 

 

(438)

68.55

7.85

12.85

164

DL-Phe-DL-Ala -N2H3

47

229-31

0.82

-

C25H34N4O3

68.49

7.76

12.78

 

 

 

 

 

 

(438)

68.55

7.85

12.85

165

DL-Phe-L-Val -N2H3

57

215-17

0.60

+240

C27H38N4O3

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.60

8.23

12.10

166

DL-Phe-DL_Val -N2H3

64

218-20

0.61

-

C27H38N4O3

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.60

8.23

12.10

167

DL-Phe-DL-Leu -N2H3

52

229-31

0.58

-

C28H40N4O4

70.00

8.33

11.66

 

 

 

 

 

 

(480)

70.10

8.38

11.73

168

DL-Phe-DL-Phe -N2H3

55

218-20

0.64

-

C31H38N4O3

72.37

7.59

10.89

 

 

 

 

 

 

(514)

72.45

7.65

10.95

169

DL-PheD-L-Ser -N2H3

60

216-18

0.68

-

C25H34N4O4

60.07

7.48

12.33

 

 

 

 

 

 

(454)

60.15

7.55

12.38

170

DL-Phe-DL-Met-N2H3

63

238-40

0.58

--

C27H38N4O3S

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.59

8.21

12.10

 

Compd.No.

X

Yield%

M.P.C

RF

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

171

DL-Met-Gly-N2H3

54

210-12

0.65

-

C20H32N4O3S

58.82

7.84

13.72

 

 

 

 

 

 

(408)

58.89

7.92

1379

172

DL-Met -β-Ala-N2H3

58

227-29

0.64

-

C21H34N4O3S

59.71

8.05

13.27

 

 

 

 

 

 

422)

59.78

8.12

13.35

173

DL-Met-DL-Ala-N2H3

68

229-31

0.55

-

C21H34N4O3S

59.71

8.05

13.27

 

 

 

 

 

 

422)

59.78

8.12

12.44

174

DL-Met-L-Val-N2H3

63

225-27

0.46

+310

C23H38N4O3S

61.33

8.44

12.44

 

 

 

 

 

 

(450)

61.38

8.52

12.53

175

DL-Met-DL-Val-N2H3

54

128-30

0.60

-

C23H38N4O3S

61.33

8.44

12.44

 

 

 

 

 

 

(450)

61.38

8.52

12.53

176

DL-Met-DL-Leu-N2H3

58

234-36

0.60

-

C24H40N4O3S

62.06

8.62

12.06

 

 

 

 

 

 

(464)

62.12

8.70

12.10

177

DL-Met-DL-Phe-N2H3

58

235-37

0.54

-

C27H38N4O3S

65.06

7.75

11.24

 

 

 

 

 

 

(498)

65.12

7.83

11.32

178

DL-Met-DL-Ser-N2H3

63

230-32

0.42

-

C21H34N4O4S

57.53

7.76

12.78

 

 

 

 

 

 

(438)

57.62

7.85

12.86

179

DL-Met–DL-Met-N2H3 

68

234-36

0.83

-

C23H38N4O3S2

57.26

7.88

11.61

 

 

 

 

 

 

(482)

57.35

7.95

1172

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula(MW)

Elemental analysis %

Calculated/Found

C

H

N

18

Gly-Gly-OMe

80

108-10

0.27

-

C18H26N2O4

64.76

7.78

8.38

 

 

 

 

 

 

(334)

64.80

7.82

9.49

19

GLy-β-Ala-OMe

75

113-15

0.74

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.66

8.10

8.10

20

GLy-DL-Ala-OMe

53

110-12

0.80

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.66

8.10

8.10

21

GLy- L-Val-OMe

65

118-20

0.71

158+

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.58

7.50

22

Gly-DL-Val-OMe

70

115-17

0.75

-

C18H28N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.58

7.50

23

Gly-DL-Leu-OMe

80

125-27

0.70

-

C22H34N2O4

(390)

67.69

67.75

8.71

8.75

7.17

7.25

24

GLy-DL-Phe-OMe

60

135-37

0.58

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.83

7.62

6.65

25

GLy-DL-Ser-OMe

55

136-38

0.75

-

C19H28N2O4

62.63

7.69

7.69

 

 

 

 

 

 

(364)

62.70

7.74

7.75

26

GLy-DL-Met-OMe

63

126-28

0.66

-

C21H32N2O4S

61.76

7.65

6.86

 

 

 

 

 

 

(408)

61.78

7.68

6.99

 

Compd.No.

X

Yield%

M.P.0C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

27

β-Ala-GLy-OMe

   80

139-41

0.50

-

C19H28N2O4

65..51

8.04

8.04

 

 

 

 

 

 

(348)

65.58

8.10

8.10

28

β-Ala- β -ALa-OMe

   80

140-42

0.75

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.32

7.85

29

β -Ala- DL-ALa-OMe

80

136-38

0.59

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.32

7.85

30

β- Ala -L-Val -OMe

52

128-30

0.50

210+

C22H34N2O4

62.68

6.46

6.96

 

 

 

 

 

 

(390)

62.79

6.58

7.10

31

β -Ala- DL-Val -OMe

74

212-14

0.93

-

C22H34N2O4

62.68

6.46

6.96

 

 

 

 

 

 

(390)

62.79

6.58

7.10

32

β -Ala-DL-Leu -OMe

60

152-54

0.95

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.95

6.99

33

β-Ala-DL-Phe -OMe

83

156-58

0.82

-

C26H34N2O4

71.23

7.93

6.39

 

 

 

 

 

 

(438)

71.30

8.00

6.45

34

β-Ala-DL-Ser -OMe

65

148-50

0.67

-

C20H30N2O5

66.66

7.93

7.40

 

 

 

 

 

 

(378)

63.49

7.99

7.45

35

β-Ala-DL-Met -OMe

55

160-62

0.70

-

C22H34N2O4S

62.55

8.05

6.63

 

 

 

 

 

 

(422)

62.60

8.10

6.70

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

36

DL-Val-Gly-OMe

80

149-51

0.82

-

C21H32N2O4

67. 02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.60

7.50

37

DL-Val-β-Ala-OMe

85

155-57

0.56

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.75

7.25

38

DL-Val-DL- Ala-OMe

70

150-52

0.94

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.75

7.25

39

DL-Val-L-Val-OMe

68

125-27

0.50

215+

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

40

DL-Val-DL-Val-OMe

72

129-31

0.92

-

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

41

DL-Val-DL-Leu-OMe

80

134-36

.800

-

C25H40N2O4

69.44

9.25

6.48

 

 

 

 

 

 

(432)

69.50

9.30

6.54

42

DL-Val-DL-Phe-OMe

75

128-30

0.36

-

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

43

DL-Val-DL-Ser-OMe

72

132-34

0.93

-

C22H34N2O4

65.02

6.89

6.89

 

 

 

 

 

 

(406)

65.10

6.95

6.95

44

DL-Val-DL-Met-OMe

82

154-56

0.87

-

C24H38N2O4

64.0

8.44

6.22

 

 

 

 

 

 

(450)

64.10

8.49

6.28

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

45

DL-Leu-Gly-OMe

75

160-62

0.75

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.75

7.25

46

DL-Leu- β –Ala-OMe

80

158-60

0.66

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

6.99

47

DL-Leu-DL-Ala-OMe

7075

166-68

0.84

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

6.99

48

DL-Leu L-Val-OMe

60

142-44

0.60

310+

C25H40N2O4

69.44

9..25

6.48

 

 

 

 

 

 

(432)

69.50

9.30

6.55

49

DL-Leu-DL-Val-OMe

75

154-56

0.82

-

C25H40N2O4

69.44

9..25

6.48

 

 

 

 

 

 

(432)

69.50

9.30

6.55

50

DL-Leu-DL-Leu-OMe

82

148-50

0.46

-

C26H39N2O4

70.42

8.80

6.48

 

 

 

 

 

 

(443)

70.48

8.85

6.54

51

DL-Leu-DL-Phe-OMe

68

160-62

083

-

C29H40N2O4

72.50

8.33

5.83

 

 

 

 

 

 

(480)

72.55

8.40

5.90

52

DL-Leu-DL-Ser-OMe

74

195-97

0.92

-

C23H35N2O4

65.87

8.35

5.83

 

 

 

 

 

 

(419)

65.93

8.40

5.90

53

DL-Leu-DL-Met-OMe

65

180-82

0.78

-

C25H40N2O4S

64.65

8.62

6.03

 

 

 

 

 

 

(464)

64.70

8.67

6.09

 

Compd.

No.

X

Yield%

M.P.0C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

54

DL-Phe-Gly -OMe

58

157-59

0.65

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.85

7.60

6.65

55

DL-Phe-β-Ala -OMe

70

158-60

0.70

-

C26H34N2O4

71.23

7.76

6.39

 

 

 

 

 

 

(438)

71.30

7.80

6.45

56

DL-Phe-DL-Ala -OMe

75

160-62

0.64

-

C26H34N2O4

71.23

7.76

6.39

 

 

 

 

 

 

(438)

71.30

7.80

6.45

57

DL-Phe-L-Val -OMe

68

175-77

0.65

250+

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

58

DL-Phe-DL_Val -OMe

84

175-77

0.85

-

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

59

DL-Phe-DL-Leu -OMe

65

190-92

0.90

-

C29H40N2O4

72.50

8.33

5.83

 

 

 

 

 

 

(480)

72.55

8.40

5.90

60

DL-Phe-DL-Phe -OMe

90

204-06

0.75

-

C32H38N2O4

74.70

7.39

5.44

 

 

 

 

 

 

(514)

74.75

5.75

549

61

DL-Phe-DL-Ser -OMe

68

212-14

0.72

-

C26H34N2O4

68.72

7.48

6.16

 

 

 

 

 

 

(454)

68.75

7.54

6.22

62

DL-Phe-DL-Met- OMe

58

213-15

0.65

-

C28H38N2O4S

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.08

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

63

DL-Met-Gly-OMe

48

162-64

0.40

-

C21H32N2O4S

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.80

7.94

6.94

64

DL-Met -β-Ala-OMe

67

147-49

0.65

-

C22H34N2O4S

60.00

5.55

6.63

 

 

 

 

 

 

(422)

62.55

8.05

6.68

65

DL-Met-DL-Ala-OMe

70

149-51

0.49

-

C22H34N2O4S

60.00

5.55

6.63

 

 

 

 

 

 

(422)

62.55

8.05

6.68

66

DL-Met-L-Val-OMe

42

201-03

0.40

280+

C24H38N2O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.05

8.50

6.30

67

DL-Met-DL-Val-OMe

64

203-05

0.83

-

C24H38N2O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.05

8.50

6.30

68

DL-Met-DL-Leu-OMe

50

137-39

0.85

-

C25H40N2O4S1

64.65

8.62

6.03

 

 

 

 

 

 

(464)

63.55

8.68

6.10

69

DL-Met-DL-Phe-OMe

73

223-25

0.72

-

C28H38N2O4S

67.46

7.63

5.62

 

 

 

 

 

 

(498)

67.55

7.70

5.70

70

DL-Met-DL-Ser-OMe

55

202-04

0.57

-

C22H34N2O5S

60.27

7.76

6.39

 

 

 

 

 

 

(438)

60.35

7.80

6.45

71

DL-Met-Met -OMe

45

222-24

0.60

-

C24H38N2O4S

59.75

7.88

5.80

 

 

 

 

 

 

(482)

59.85

7.94

5.95

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

72

Gly-Gly

65

156-58

0.59

-

C17H24N2O4

63.75

7.50

8.75

 

 

 

 

 

 

(320)

63.80

7.55

8.80

73

GLy-β-Ala

80

163-65

0.84

-

C18H26N2O4

64.67

7.78

8.38

 

 

 

 

 

 

(334)

64.75

7.85

8.45

74

GLy-DL-Ala

85

162-64

0.68

-

C18H26N2O4

64.67

7.78

8.38

 

 

 

 

 

 

(334)

64.75

7.85

8.45

75

GLy- L-Val

68

174-76

0.50

160+

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.35

7.80

76

GLy-DL-Val

78

175-77

0.84

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.35

7.80

77

Gly-DL-Leu

65

140-42

0.86

-

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

76.10

8.59

7.50

78

GLy-DL-Phe

85

182-84

0.73

-

C24H30N2O4

70.24

7.31

6.82

 

 

 

 

 

 

(410)

70.30

7.38

6.90

79

GLy-DL-Ser

70

176-78

0.76

-

C18H26N2O4

61.71

7.42

8.00

 

 

 

 

 

 

(350)

61.79

7.49

8.07

80

GLy-DL-Met

60

195-97

0.79

-

C20H30N2O4

60.91

7.61

7.10

 

 

 

 

 

 

(394)

60.96

7.69

7.15

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

81

β-Ala-GLy

53

164-66

0.55

-

C18H26N2O4

64.67

7.78

8.38

 

 

 

 

 

 

(334)

64.73

7.83

8.43

82

β-Ala- β -ALa

72

192-95

0.65

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.56

8.10

8.10

83

β -Ala- DL-ALa

75

194-96

0.54

-

C19H28N2O4

65.51

8.04

8.04

 

 

 

 

 

 

(348)

65.56

8.10

8.10

84

β- Ala- L-Val

47

215-17

0.55

+340

C21H32N2O4

67.02

8.51

6.96

 

 

 

 

 

 

(376)

67.10

8.60

7.44

85

β -Ala- DL-Val

69

212-14

0.80

-

C21H32N2O4

67.02

8.51

6.96

 

 

 

 

 

 

(376)

67.10

8.60

7.44

86

β -Ala-DL-Leu

55

149-51

0.85

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.76

7.20

87

β-Ala-DL-Phe

78

221-23

0.60

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.81

7.60

6.68

88

β-Ala-DL-Ser

60

154-56

0.67

-

C19H28N2O5

62.63

7.69

7.69

 

 

 

 

 

 

(364)

62.68

7.75

7.76

89

β-Ala-DL-Met

53

184-86

0.50

-

C21H32N2O4

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.85

7.90

6.90

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

90

DL-Val-Gly

73

158-60

0.75

-

C20H30N2O4

66.29

8.28

7.73

 

 

 

 

 

 

(362)

66.35

8.35

7.88

91

DL-Val-β-Ala

76

222-24

0.60

-

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.60

7.50

92

DL-Val-DL- Ala

48

215-17

0.52

-

C21H32N2O4

67.02

8.51

7.44

 

 

 

 

 

 

(376)

67.10

8.60

7.50

93

DL-Val-L-Val

70

135-37

0.93

+230

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

7.10

94

DL-Val-DL-Val

60

134-36

0.94

-

C23H36N2O4

68.31

8.91

6.93

 

 

 

 

 

 

(404)

68.38

8.99

7.10

95

DL-Val-DL-Leu

79

138-40

0.83

-

C24H38N2O4

68.89

9.09

6.93

 

 

 

 

 

 

(418)

68.95

9.15

7.10

96

DL-Val-DL-Phe

61

155-57

0.78

-

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452)

71.75

8.05

6.25

97

DL-Val-DL-Ser

51

200-02

0.72

-

C21H32N2O5

64.28

8.16

7.14

 

 

 

 

 

 

(392)

64.35

8.22

7.20

98

DL-Val-DL-Met

54

203-05

0.54

-

C23H36N2O4S

63.30

8.25

6.42

 

 

 

 

 

 

(436)

63.38

8.34

6.48

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

99

DL-Leu-Gly

85

160-62

0.70

-

C21H32N2O4

67.02

8.71

7.44

 

 

 

 

 

 

(376)

67.08

8.79

7.55

100

DL-Leu- β –Ala

89

178-80

0.54

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.80

7.25

101

DL-Leu-DL-Ala

50

180-82

0.45

-

C22H34N2O4

67.69

8.71

7.17

 

 

 

 

 

 

(390)

67.75

8.80

7.25

102

DL-Leu L-Val

70

146-48

0.88

+180

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

103

DL-Leu-DL-Val

54

148-50

0.90

-

C24H38N2O4

68.89

9.09

6.69

 

 

 

 

 

 

(418)

68.95

9.15

6.75

104

DL-Leu-DL-Leu

76

157-59

0.77

-

C25H37N2O4

69.93

8.62

6.52

 

 

 

 

 

 

(429)

69.99

8.69

6.62

105

DL-Leu-DL-Phe

60

207-09

0.62

-

C28H38N2O4

72.10

8.15

6.00

 

 

 

 

 

 

(466)

72.15

8.20

6.10

106

DL-Leu-DL-Ser

53

200-02

0.65

-

C22H33N2O4

65.18

8.14

6.91

 

 

 

 

 

 

(405)

65.25

8.20

7.03

107

DL-Leu-DL-Met

70

201-03

0.76

-

C24H38N4O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.05

8.50

6.28

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

108

DL-Phe-Gly

65

145-47

0.77

-

C24H30N2O4

70.24

7.31

6.82

 

 

 

 

 

 

(410)

70.30

7.38

6.88

109

DL-Phe-β-Ala

75

165-67

0.61

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.80

7.60

6.66

110

DL-Phe-DL-Ala

80

168-70

048

-

C25H32N2O4

70.75

7.54

6.60

 

 

 

 

 

 

(424)

70.80

7.60

6.66

111

DL-Phe-L-Val

85

180-82

0.90

+270

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452)

71.75

7.99

6.25

112

DL-Phe-DL_Val

65

180-82

0.51

-

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452)

71.75

7.99

6.25

113

DL-Phe-DL-Leu

75

210-12

0.31

-

C28H38N2O4

72.10

5.55

15.55

 

 

 

 

 

 

(466)

72.15

8.15

6.00

114

DL-Phe-DL-Phe

75

212-14

0.31

-

C31H36N2O4

74.40

7.20

5.60

 

 

 

 

 

 

(500)

74.50

7.30

5.65

115

DL-Phe-DL-Ser

70

205-07

0.42

-

C25H32N2O5

74.40

7.27

6.36

 

 

 

 

 

 

(440)

74.45

7.32

6.40

116

DL-Phe-DL-Met

73

220-22

0.66

-

C27H36N2O4

71.68

7.96

6.19

 

 

 

 

 

 

(452­)

71.75

8.01

6.25

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

117

DL-Met-Gly

73

182-84

0.71

-

C20H30N2O4S

61.91

7.61

7.10

 

 

 

 

 

 

(394)

61.99

7.66

7.15

118

DL-Met -β-Ala

67

215-17

0.71

-

C21H32N2O4S

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.80

7.90

6.90

119

DL-Met-DL-Ala

77

229-31

0.55

-

C21H32N2O4S

61.76

7.84

6.86

 

 

 

 

 

 

(408)

61.80

7.90

6.90

120

DL-Met-L-Val

82

217-19

0.42

+160

C23H36N2O4S

63.30

8.25

6.42

 

 

 

 

 

 

(436)

63.35

8.30

6.50

121

DL-Met-DL-Val

87

224-26

0.84

-

C23H36N2O4S

63.30

8.25

6.42

 

 

 

 

 

 

(436)

63.35

8.30

6.50

122

DL-Met-DL-Leu

67

229-31

0.45

-

C24H38N2O4S

64.00

8.44

6.22

 

 

 

 

 

 

(450)

64.08

8.50

6.28

123

DL-Met-DL-Phe

57

218-20

0.44

-

C27H36N2O4S

66.94

7.43

5.78

 

 

 

 

 

 

(484)

66.99

7.48

5.83

124

DL-Met-DL-Ser

77

226-28

0.45

-

C21H32N2O5S

59.43

7.54

6.60

 

 

 

 

 

 

(424)

59.48

7.60

6.65

125

DL-Met–DL-Met

72

205-07

0.56

-

C23H36N2O4S2

58.97

7.69

5.98

 

 

 

 

 

 

(468)

58.99

7.75

6.09

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

126

Gly-Gly-N2H3

80

182-84

0.60

-

C17H26N4O3

61.07

7.78

16.76

 

 

 

 

 

 

(334)

61.15

7.85

16.80

127

GLy-β-Ala-N2H3

74

215-17

0.60

-

C18H28N4O3

62.06

8.04

16.09

 

 

 

 

 

 

(348)

62.10

8.10

16.15

128

GLy-DL-Ala-N2H3

76

219-21

0.55

-

C18H28N4O3

62.06

8.04

16.09

 

 

 

 

 

 

(348)

62.10

8.10

16.15

129

GLy- L-Val-N2H3

81

217-19

0.54

+320

C20H32N4O3

63.82

8.51

14.89

 

 

 

 

 

 

(376)

63.89

8.59

14.95

130

GLy-DL-Val-N2H3

80

219-21

0.83

-

C20H32N4O3

63.82

8.51

14.89

 

 

 

 

 

 

(376)

63.89

8.59

14.95

131

Gly-DL-Leu-N2H3

55

229-31

0.54

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.68

8.75

14.40

132

GLy-DL-Phe-N2H3

54

215-17

0.35

-

C24H32N4O3

67.92

7.69

13.20

 

 

 

 

 

 

(424)

67.99

7.75

13.30

133

GLy-DL-Ser-N2H3

50

222-24

0.40

-

C18H28N4O5

59.34

7.69

15.38

 

 

 

 

 

 

(364)

59.40

7.76

15.45

134

GLy-DL-Met-N2H3

79

208-10

0.48

-

C20H32N4O3S

58.82

7.84

13.72

 

 

 

 

 

 

(408)

58.94

7.93

13.78

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

135

β –Ala-Gly-N2H3

64

186-88

0.61

-

C18H28N4O3

62.06

8.04

16.09

 

 

 

 

 

 

(348)

62.10

8.10

16.15

136

β-Ala- β -ALa-N2H3

58

227-29

0.61

-

C19H30N4O3

62.98

8.28

15.46

 

 

 

 

 

 

(362)

62.99

8.35

15.55

137

β –Ala- DL-ALa-N2H3

68

228-30

0.45

-

C19H30N4O3

62.98

8.28

15.46

 

 

 

 

 

 

(362)

62.99

8.35

15.55

138

β- Ala- L-Val -N2H3

63

226-28

0.32

+250

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.70

8.80

14.40

139

β –Ala -DL-Val -N2H3

68

224-26

0.74

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.70

8.80

14.40

140

β -Ala-DL-Leu -N2H3

58

229-31

0.35

-

C22H36N4O4

65.34

8.91

13.86

 

 

 

 

 

 

(404)

65.40

9.99

13.90

141

β-Ala-DL-Phe -N2H3

48

218-20

0.35

-

C25H34N4O3

68.49

7.76

12.78

 

 

 

 

 

 

(438)

68.55

7.80

12.83

142

β-Ala-DL-Ser -N2H3

67

226-28

0.55

-

C19H30N4O4

60.31

7.93

14.81

 

 

 

 

 

 

(378)

60.38

7.99

14.89

143

β-Ala-DL-Met -N2H3

63

205-07

0.66

-

C21H34N4O3S

59.71

8.05

13.27

 

 

 

 

 

 

(422)

59.86

8.14

13.35

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula(MW)

Elemental analysis %

Calculated/Found

C

H

N

144

DL-Val-Gly-N2H3

56

190-92

0.61

-

C20H32N4O3

63.82

8.51

14.89

 

 

 

 

 

 

(376)

63.88

8.60

14.95

145

DL-Val-β-Ala-N2H3

50

219-21

0.72

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(391)

64.70

8.78

14.40

146

DL-Val-DL- Ala-N2H3

60

221-23

0.60

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(391)

64.70

8.78

14.40

147

DL-Val-L-Val-N2H3

65

227-29

0.42

+180

C23H38N4O3

66.02

9.09

13.39

 

 

 

 

 

 

(418)

66.10

9.15

13.45

148

DL-Val-DL-Val-N2H3

70

229-31

0.80

-

C23H38N4O3

66.02

9.09

13.39

 

 

 

 

 

 

(418)

66.10

9.15

13.45

149

DL-Val-DL-Leu-N2H3

50

233-35

0.63

-

C24H40N4O3

66.66

9.25

12.96

 

 

 

 

 

 

(432)

66.70

9.30

13.05

150

DL-Val-DL-Phe-N2H3

40

228-30

0.35

-

C27H38N4O3

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.58

8.20

12.10

151

DL-Val-DL-Ser-N2H3

60

235-37

0.42

-

C21H34N4O4

62.06

8.37

13.29

 

 

 

 

 

 

(406)

62.15

8.45

13.35

152

DL-Val-DL-Meth-N2H3

55

213-15

0.33

-

C23H38N4O3S

61.33

8.44

12.44

 

 

 

 

 

 

(450)

61.38

8.50

12.50

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

153

DL-Leu-Gly-N2H3

64

194-96

0.70

-

C21H34N4O3

64.61

8.71

14.35

 

 

 

 

 

 

(390)

64.70

8.80

14.40

154

DL-Leu- β –Ala-N2H3

50

210-12

0.72

-

C22H36N4O3

65.34

8.91

13.86

 

 

 

 

 

 

(404)

65.40

8.99

13.95

155

DL-Leu-DL-Ala-N2H3

55

213-15

0.54

-

C22H36N4O3

65.34

8.91

13.86

 

 

 

 

 

 

(404)

65.40

8.99

13.95

156

DL-Leu L-Val-N2H3

65

221-23

0.41

+218

C24H40N4O3

66.66

9.25

12.96

 

 

 

 

 

 

(432)

66.70

9.35

13.05

157

DL-Leu-DL-Val-N2H3

73

224-26

0.84

-

C24H40N4O3

66.66

9.25

12.96

 

 

 

 

 

 

(432)

66.70

9.35

13.05

158

DL-Leu-DL-Leu-N2H3

54

235-37

0.44

-

C25H39N4O3

67.72

8.80

12.64

 

 

 

 

 

 

(443)

67.79

8.89

12.70

159

DL-Leu-DL-Phe-N2H3

45

240-42

0.43

-

C28H40N4O3

70.00

8.33

11.66

 

 

 

 

 

 

(480)

70.05

8.40

11.70

160

DL-Leu-DL-Ser-N2H3

65

238-40

0.24

-

C22H35N4O4

63.00

8.35

13.36

 

 

 

 

 

 

(419)

63.10

8.43

13.45

161

DL-Leu-DL-Met- N2H3

58

219-21

0.35

-

C24H40N4O3S

62.06

8.62

12.06

 

 

 

 

 

 

(464

62.10

8.70

12.10

 

Compd.No.

X

Yield%

M.P.°C

RF

*

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

162

DL-Phe-Gly -N2H3

43

195-97

0.48

-

C24H32N4O3

67.92

7.54

13.20

 

 

 

 

 

 

(424)

67.99

7.60

13.28

163

DL-Phe-β-Ala -N2H3

37

226-28

0.48

-

C25H34N4O3

68.49

7.76

12.78

 

 

 

 

 

 

(438)

68.55

7.85

12.85

164

DL-Phe-DL-Ala -N2H3

47

229-31

0.82

-

C25H34N4O3

68.49

7.76

12.78

 

 

 

 

 

 

(438)

68.55

7.85

12.85

165

DL-Phe-L-Val -N2H3

57

215-17

0.60

+240

C27H38N4O3

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.60

8.23

12.10

166

DL-Phe-DL_Val -N2H3

64

218-20

0.61

-

C27H38N4O3

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.60

8.23

12.10

167

DL-Phe-DL-Leu -N2H3

52

229-31

0.58

-

C28H40N4O4

70.00

8.33

11.66

 

 

 

 

 

 

(480)

70.10

8.38

11.73

168

DL-Phe-DL-Phe -N2H3

55

218-20

0.64

-

C31H38N4O3

72.37

7.59

10.89

 

 

 

 

 

 

(514)

72.45

7.65

10.95

169

DL-PheD-L-Ser -N2H3

60

216-18

0.68

-

C25H34N4O4

60.07

7.48

12.33

 

 

 

 

 

 

(454)

60.15

7.55

12.38

170

DL-Phe-DL-Met-N2H3

63

238-40

0.58

--

C27H38N4O3S

69.52

8.15

12.01

 

 

 

 

 

 

(466)

69.59

8.21

12.10

 

Compd.No.

X

Yield%

M.P.°C

RF

Molecular Formula

(MW)

Elemental analysis %

Calculated/Found

C

H

N

171

DL-Met-Gly-N2H3

54

210-12

0.65

-

C20H32N4O3S

58.82

7.84

13.72

 

 

 

 

 

 

(408)

58.89

7.92

1379

172

DL-Met -β-Ala-N2H3

58

227-29

0.64

-

C21H34N4O3S

59.71

8.05

13.27

 

 

 

 

 

 

422)

59.78

8.12

13.35

173

DL-Met-DL-Ala-N2H3

68

229-31

0.55

-

C21H34N4O3S

59.71

8.05

13.27

 

 

 

 

 

 

422)

59.78

8.12

12.44

174

DL-Met-L-Val-N2H3

63

225-27

0.46

+310

C23H38N4O3S

61.33

8.44

12.44

 

 

 

 

 

 

(450)

61.38

8.52

12.53

175

DL-Met-DL-Val-N2H3

54

128-30

0.60

-

C23H38N4O3S

61.33

8.44

12.44

 

 

 

 

 

 

(450)

61.38

8.52

12.53

176

DL-Met-DL-Leu-N2H3

58

234-36

0.60

-

C24H40N4O3S

62.06

8.62

12.06

 

 

 

 

 

 

(464)

62.12

8.70

12.10

177

DL-Met-DL-Phe-N2H3

58

235-37

0.54

-

C27H38N4O3S

65.06

7.75

11.24

 

 

 

 

 

 

(498)

65.12

7.83

11.32

178

DL-Met-DL-Ser-N2H3

63

230-32

0.42

-

C21H34N4O4S

57.53

7.76

12.78

 

 

 

 

 

 

(438)

57.62

7.85

12.86

179

DL-Met–DL-Met-N2H3 

68

234-36

0.83

-

C23H38N4O3S2

57.26

7.88

11.61

 

 

 

 

 

 

(482)

57.35

7.95

1172

 

RESULT AND DISCUSSION:

Chemistry

4-isobutylhydrotropoyl amino acids (12-17) were easily synthesized by coupling of 4-isobutylhydrotropoyl (Ibuprofen) acid chloride (11) with amino acids in sodium hydroxide-benzene medium. First, amino acids were dissolved in 1N-NaOH solution and cooled to 10 °C solution (A), 4-isobutylhydrotropoyl (Ibuprofen) acid chloride (11) was dissolved in benzene (solution B). Solution (A) added gradually with stirring to solution (B)  during 75 mins. After complete addition, the stirring was continued for 3 additional hrs. at room temperature. The aqueous layer was separated, and acidified with 2N-HCl to pH=5 to give the desired compounds (12-17). The crude products (12-17) were purified by recrystallization from ethanol–water and obtained in yields (75-95 %).

 

4-isobutylhydrotropoyl  dipeptide methyl esters  (18-71) were prepared by carbodiimide method(5) which considered the most suitable method for the preparation of these compounds and no side reactions observed. Many scientists confirmed that in peptide synthesis (6-10).

 

4-isobutylhydrotropoyl amino acid (12-17) was coupled with amino acid methyl ester hydrochlorides [1-9; 1:1 molar ratio] by carbodiimide technique (5).  First, 4-isobutyl-hydrotropoyl amino acid (12-17)  was dissolved in tetrahydrofuran and cooled to 0°C (Solution A). The amino acid methyl ester hydrochlorides (1-9) were suspended in THF and triethylamine, and then the mixture stirred for 30 min. at (0 °C), the triethylamine hydrochloride was filtered off (Solution B). (Solution A) was added to (solution B) and N,N\-dicyclohexyl carbodiimide (DCC) was added (as the same ratio of amino acid methyl ester hydrochlorides) at     (0 °C). The mixture was stirred at (0°C) for  4-6 hrs., and left over night and the time of the reaction was controlled by TLC. The precipitated dicyclohexylurea(DCC) was filtered off, and the filtrate evaporated in vacuum. The residual material was purified from ethanol-water.  The compounds (18-71) were obtained in yields (52-83%).

 

4-isobutyl-hydrotropoyl dipeptides (72-125) were prepared by adding 4-isobutylhydrotropoyl  dipeptide  methyl     ester (18-71); 0.001mole) was added to a solution of 0.5-N NaOH. and refluxed the mixture with continuous stirring for 1 hour ON water bath. The reaction mixture was allowed to cool, then acidified with 1N-HCl to pH=5. The crude compounds (72-125) were separated, filtered, recrystallized from ethanol-water, and obtained in (52-86%) yields.

 

4-isobutylhydrotropoyl dipeptides hydrazides (126-179)

The titled compounds (126-179) were synthesized by the action of hydrazine hydrate in presence of ethyl alcohol on the corresponding 4-isobutylhydrotropoyl dipeptide methyl ester (18-71). The reaction mixture was heated on water bath for ½ hr. and left 24 hrs at °C. The crude hydrazides (126-179) were separated out, recrystallized from ethanol-water, and obtained in good yields (55-85%).

 

The biological activities of the synthesized compounds :-

The biological activities of the synthesized compounds (12-179) were tested using the hole plate and filter paper disk methods(11-14). All the compounds (12-179) were tested against different types of bactria (Gram-positive and Gram-negative bacteria) as follow:

A.     Pseudomonas aeruginosa.

B.     E. Coli.

C.     Bacillus Subtilis.

D.     Staphyococus.

And, Ampicillin was used as a reference compound (c.f. Table 1).

Also, all the synthesized compounds (12-179) were tested against different types of fungi as follow:

A.     Asprigillus flavus.

B.     Asprigillus niger.

 

And, Claforan was used as a reference compound (c.f.Table1).

From table (1), we found the following:-

1.      The starting materials (13 and 14) were found to possess a inactivities against pseud ,B. Subtilis . (c.f.Table1).

2.      The compounds (31-51) were found to be  Moderate active or have a very weak activity against all tested microorganisms, at MIC  >500 μg/ml (c.f.Table1).

 

From the above results, we concluded  that the combination of Ibuprofen moiety  with different  amino acids or peptides residues gave Moderate active compounds against all tested .

 

 

Table (1):Antimicrobial  activities of the synthesized compounds (12-179):

Aspero. fl

Aspero. n

Staph

B-sutlas

E-coli

Pseudo

Comp No.

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

 

–

 

–

500

+

 

–

500

+

 

-

16

 

 

 

 

500

+

 

 

500

+

 

-

17

 

–

 

–

500

+

 

–

500

+

 

-

18

 

–

 

–

500

+

 

–

250

++

 

-

19

 

–

 

–

250

++

 

–

 

-

 

-

20

 

–

 

–

500

+

 

–

 

-

 

-

21

 

–

 

–

500

+

 

–

 

-

 

-

22

 

–

 

–

500

+

 

–

 

-

 

-

32

 

–

 

–

500

+

 

–

500

+

 

-

33

 

–

 

–

500

+

 

–

500

+

 

-

34

 

–

 

–

500

+

 

–

250

++

 

-

35

 

–

 

–

250

++

 

–

500

+

 

-

36

 

–

 

–

500

+

 

–

500

+

 

-

37

 

–

 

–

 

-

 

–

500

+

 

-

38

 

–

 

–

500

+

 

–

500

+

 

-

39

 

–

 

–

 

-

 

–

500

+

 

-

40

 

–

 

–

 

-

 

–

500

+

 

-

41

 

–

 

–

 

-

 

–

250

++

 

-

42

 

–

 

–

500

+

 

–

500

+

 

-

43

 

–

 

–

500

+

 

–

500

+

 

-

44

 

–

 

–

250

++

 

–

500

+

 

-

45

 

–

 

–

500

+

 

–

500

+

 

-

46

 

–

 

–

 

-

 

–

500

+

 

-

47

 

–

 

–

 

-

 

–

500

+

 

-

48

 

–

 

–

 

-

 

–

250

++

 

-

49

 

–

 

–

 

-

 

–

500

+

 

-

50

 

–

 

–

 

-

 

–

500

+

 

-

51

 

–

 

–

 

-

 

–

500

+

 

-

52

 

–

 

–

 

-

 

–

500

+

 

-

53

 

–

 

–

500

+

 

–

500

+

 

-

54

 

–

 

–

250

++

 

–

500

+

 

-

55

 

–

 

–

500

+

 

–

500

+

 

-

56

 

–

 

–

500

+

 

–

500

+

 

-

57

MIC=  Minimal inhibitory concentration;  Antimicrobial activities= A;  Inactive compound or its MIC>500 μ/ml= -  ; Weak activity= +; Moderate activity= ++; High activity= +++

 

Aspero. fl

Aspero .n

Staph

B-sutilis

E-coli

Pseudo

Comp

No.

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

 

–

 

–

 

-

 

-

250

++

 

-

58

 

 

 

 

 

-

 

-

250

+

 

-

59

 

–

 

–

 

-

 

-

500

+

 

-

60

 

–

 

–

 

-

 

-

500

+

 

-

61

 

–

 

–

 

-

 

-

250

++

 

-

62

 

–

 

–

 

-

 

-

500

+

 

-

63

 

–

 

–

 

-

 

-

500

+

 

-

64

 

–

 

–

 

-

 

-

500

+

 

-

65

 

–

 

–

 

-

 

-

 

-

500

+

66

 

–

 

–

 

-

 

-

 

-

 

-

67

 

–

 

–

 

-

500

+

 

-

 

-

68

 

–

 

–

 

-

500

+

 

-

 

-

69

 

–

 

–

 

-

 

-

 

-

 

-

77

 

–

 

–

 

-

250

++

 

-

 

-

78

 

–

 

–

 

-

500

+

 

-

 

-

79

 

–

 

–

 

-

500

+

 

-

 

-

80

 

–

 

–

500

+

500

+

 

-

 

-

101

 

–

 

–

500

+

 

-

 

-

 

-

116

 

–

 

–

250

++

 

-

 

-

250

++

117

 

–

 

–

500

+

 

-

 

-

250

++

118

 

–

 

–

500

+

 

-

 

-

 

-

119

 

–

 

–

500

+

 

-

 

-

500

+

120

 

–

 

–

 

-

 

-

 

-

 

-

121

 

–

 

–

 

-

 

-

 

-

 

-

122

 

–

 

–

 

-

500

+

 

-

500

+

123

 

–

 

–

 

-

500

+

500

+

500

+

124

 

–

 

–

 

-

 

-

500

+

500

+

132

 

–

 

–

500

+

 

-

500

+

500

+

133

 

–

 

–

500

+

 

-

 

-

500

+

134

 

–

 

–

500

+

 

-

 

-

500

+

135

 

–

 

–

500

+

 

-

 

-

250

+

136

 

–

 

–

500

+

 

-

 

-

500

+

137

 

–

 

–

500

+

 

  -

 

 -

500

+

138

MIC=  Minimal inhibitory concentration;     Antimicrobial activities= A; Inactive compound or its MIC>500 μ/ml= -; Weak activity= +; Moderate activity= ++; High activity= +++

 

Aspero. fl

Aspero .n

Staph

B-sutilis

E-coli

Pseudo

Comp

No.

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

M.I.C

A

 

–

 

–

500

+

 

 -

 

 -

500

+

139

 

 

 

 

500

+

 

 -

 

 -

500

+

140

 

–

 

–

 

 -

 

 -

 

 -

 

 -

141

 

–

 

–

500

+

 

 -

 

 -

 

 -

142

 

–

 

–

500

+

 

 -

 

 -

 

 -

143

 

–

 

–

500

+

 

 -

 

 -

 

 -

144

 

–

 

–

500

+

 

 -

 

 

 

 -

145

 

–

 

–

500

+

 

 -

500

+

500

+

146

 

–

 

–

500

+

 

 -

500

+

250

++

147

 

–

 

–

500

+

 

 -

500

+

500

+

148

 

–

 

–

500

+

 

 -

250

++

500

+

149

 

–

 

–

 

 -

 

 -

500

+

500

+

150

 

–

 

–

500

+

 

 -

 

 -

500

+

151

 

–

 

–

500

+

 

 -

 

 -

500

+

152

 

–

 

–

500

+

 

 -

 

 -

500

+

153

 

–

 

–

500

+

 

 -

 

 -

500

+

154

 

–

 

–

500

+

 

 -

 

 -

500

+

155

 

–

 

–

 

 -

 

 -

 

 -

 

 -

156

 

–

 

–

 

 -

 

 -

500

+

 

 -

157

 

–

 

–

 

 -

 

 -

 

 -

 

 -

158

 

–

 

–

 

 -

 

 -

 

 -

 

 -

159

 

–

 

–

500

+

 

 -

 

 -

 

 -

160

 

–

 

–

500

+

 

 -

 

 -

 

 -

161

 

–

 

–

500

+

 

 -

 

 -

 

 -

162

 

–

 

–

500

+

 

 -

 

 -

 

 -

163

 

–

 

–

 

 -

 

 -

 

 -

 

 -

164

 

–

 

–

 

 -

 

 -

 

 -

 

 -

165

 

–

 

–

 

 -

 

 -

500

+

 

 -

166

 

–

 

–

 

 -

 

 -

 

 -

 

 -

167

 

–

 

–

 

 -

 

 -

 

 -

 

 -

168

 

–

 

–

500

+

 

 -

500

+

500

+

169

 

–

 

–

500

+

 

 -

500

+

500

+

170

 

–

 

–

500

+

 

 -

250

++

500

+

171

MIC=  Minimal inhibitory concentration;     Antimicrobial activities= A; Inactive compound or its MIC>500 μ/ml= -; Weak activity= +; Moderate activity= ++; High activity= +++

 

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2.       T. M. Ibrahim, Al-Azhar Bull. Sci., 241, 65 (1991).

3.       T. M. Ibrahim, A. A. Shabana and H. A. Hammad, Arch. Pharm. Sci., 15 (2), 130     (1992).

4.       A. A. Magdel-din, H. M. Abou-Yossef and T. M.    Ibrahim Phosph. Sulpher and Silicon J., 68,297                (1992).

5.       J. C. Sheehan, M. Goodman, and G. P. Hess, J. Am. Chem. Soc., 78, 1367 (1956).

6.       H. Asyagi, T. Kats, M. Ohno, M. Kondo and N. J. Izumiya, J. Am. Chem. Soc. 86, 5700(1964).

7.       M. Bondanseky, M. A. Ondetti, C. A. Brickhimer, and P. L. Thomas, J. Am. Chem. Soc., 86,4452(1964).

8.       P. A. Cruickshank and J. C. Sheehan, J. Am. Chem. Soc., 86, 2070(1964).

9.       M. Goodman, B. Bery, and A. E. Lanzillotti, J. Am. Chem. Soc., 86,1880(1964).

10.     K. Hofman, W. Hass, G. Zanetti, J. Am. Chem. Soc., 77,3419(1957).

11.     T. Curtius, and F. Goebel, J. Prakt. Chem. 37(2),150(1888).

12.     A.L. Banker, and G.S. Skinner, J.Am.Chem. Soc., 46,403(1925).

13.     E. Fischer, and W.A. Jacobs, Ber,39,2943(1906).

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Received on 04.03.2014         Modified on 01.04.2014

Accepted on 08.04.2014         © AJRC All right reserved

Asian J. Research Chem. 7(5): May 2014; Page 466-482