254 nm, flow rate 1.0 mL/min, and solvents 50/50 MeOH/H20 containing 0.1% TFA).

Tripeptides 5.4b, 5.4e, and 5.4f are novel compounds, and were characterized by 1H and

13C NMR spectroscopy, elemental analysis, and optical rotation.

Table 5-4. Preparation of N-Z-tripeptides (i) from N-(Z-aminoacyl)benzotriazoles and
 unprotected dipeptides (with 5.1a-c) (ii) from N-(Z-
 dipeptidoyl)benzotriazoles and unprotected amino acids (with 5.3a and 5.3b).
RCOBt amino acid Product yield Ref.
reactant or dipeptide (%)

5.1a Gly-Leu Z-Ala-Gly-Leu-OH (5.4a) 93 --
5.1d Gly-Leu Z-DL-Ala-Gly-Leu-OH (5.4a+5.4a') 94
5.1b Gly-Leu Z-Val-Gly-Leu-OH (5.4b) 85 [79CB2145]
5.1c Gly-Gyl Z-Phe-Gly-Gly-OH (5.4c) 98 [91SL35]
5.3a Ala Z-Phe-Ala-Ala-OH (5.4d) 92
5.3a Ser Z-Phe-Ala-Ser-OH (5.4e) 94
5.3b Try Z-Ala-Phe-Try-OH (5.4f) 95


5.2.5 Preparation of N-Z-Tetrapeptides.

 Reactions of 5.3a and 5.3b with Gly-L-Leu-OH for 2-4 h gave tetrapeptides 5.5a

and 5.5b in 86% and 85% yields, respectively (Table 5-5). These novel compounds were

characterized by 1H and 13C NMR spectroscopy, elemental analysis, and optical rotation.

Table 5-5. Preparation of N-Z-tetrapeptides from N-(Z-dipeptidoyl)benzotriazoles and an
 unprotected dipeptide.
 RCOBt dipeptide Product yield
 reactant (%)
 5.3a Gly-Leu Z-Phe-Ala-Gly-Leu-OH (5.5a) 86
 5.3b Gly-Leu Z-Ala-Phe-Gly-Leu-OH (5.5b) 85

 5.3 Conclusion

 In summary, N-acylbenzotriazoles derived from N-protected amino acids or

peptides have been introduced as new coupling reagents. The peptide coupling reaction

utilizing the N-acylbenzotriazole derivatives and unprotected amino acids proceeds with

minimal epimerization in partially aqueous solution under mild conditions.