Amino Acids and Peptides in Ball Milling - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 134

Table 6.1 Mechanosynthesis of a,a-dipeptides from a-UNCAs and a-aminoesters.

O

R 2

R 2

O

GP

N

N NaHCO 3 (1.5 equiv)

OR 3

OR 3

O

+ CO 2 + NaCl

AH ·

GP H

H 2 N

Vibrating ball-mill, 30 Hz, 1 h

R 1

R 1

O

O

O

a , a -Dipeptides

a -UNCAs a -Aminoesters

Entry a-UNCA a-Aminoesters a,a-Dipeptides Conversion (%) Yield (%)

HCl H-Ala-OtBu

1 Boc-Phe-NCA Boc-Phe-Ala-OtBu 100 73

HCl H-Leu-OMe

2 Boc-Phe-Leu-OMe 85 —

HCl H-Leu-OtBu

3 Boc-Phe-Leu-OtBu 100 70

4 HCl H-Phe-OMe Boc-Phe-Phe-OMe 58 55

5 AcOH H-Gly-OtBu Boc-Phe-Gly-OtBu 100 90

6 Boc-Val-NCA HCl H-Leu-OMe Boc-Val-Leu-OMe 100 87

7 HCl H-Leu-OtBu Boc-Val-Leu-OtBu 97 85

8 HCl H-Ala-OMe Boc-Val-Ala-OMe 100 100

9 HCl H-Ala-OtBu Boc-Val-Ala-OtBu 100 100

10 HCl H-Phe-OMe Boc-Val-Phe-OMe 100 88

11 Fmoc-Val-NCA HCl H-Leu-OMe Fmoc-Val-Leu-OMe 90 —

12 HCl H-Leu-OtBu Fmoc-Val-Leu-OtBu 92 —

13 HCl H-Ala-OMe Fmoc-Val-Ala-OMe 100 76

14 HCl H-Ala-OtBu Fmoc-Val-Ala-OtBu 78 —

15 HCl H-Phe-OMe Fmoc-Val-Phe-OMe 93 —