R O 0
 R O i) R1 O ii R2
 Z-NH HN
 Z-NH OH Z-NH Bt O
 HO
 5.1a-d 5.2a-i

 iv) iii)

 Ri 0 Ri 0
 NHHN R1
 Z-NH HN- O / Z-NH HN-
 0 v) R vi) o
 HN Z NH HN- HN

 HO Bt HO HN
 5.4a-f, 5.4a' 0 5.3a-b 0 5.5a-b

 Z= benzyloxycarbonyl R1 = CH3, CH(CH3)2, CH2Ph
 R2 = H, CH3, CH(CH3)2, CH2Ph, CH2OH, CH2(indol-3-yl)
 Bt= benzotriazol--yl R3 = H, CH3, CH2CH(CH3)2, CH2OH, CH2(indol-3-yl)
 R4 = CH2CH(CH3)2

Scheme 5-1. Coupling reactions with N-(Z-a-aminoacyl)benzotriazoles

i) SOC12, BtH at 25 C, ii) Unprotected amino acid, Et3N in CH3CN/H20. iii) SOC12, BtH

at 0 C, iv) Gly-Leu-OH or Gly-Gly-OH, Et3N in CH3CN/H20, v) Unprotected amino

acid, Et3N in CH3CN/H20. vi) Gly-Leu-OH, Et3N in CH3CN/H20.

 5.2 Results and Discussion

5.2.1 Preparation of N-(Z-Aminoacyl)benzotriazoles from N-Z-Amino acids 5.1a-d.

 The Z group is a favorite protecting group due to (i) its stability towards both acidic

and basic conditions, (ii) easy purification of solid Z-protected amino acids and peptides,

and (iii) its ready cleavage by hydrogenation. [01SPP] [02TL7717] The Boc group is also

a popular protecting group, [64JACS1839] [97S1499] but is not preferred under strongly

acidic conditions.

Chiral 1-(c-Boc-aminoacyl)benzotriazoles were previously prepared by the reaction of

BtSO2Me with Boc-protected amino acids in refluxing THF in the presence of Et3N with