Side‐Chain‐Functionalized Dipeptides Derived from 6,5‐Fused Bicyclic Thiazolidinlactams

Condensation of D‐arabinuronolactone (2) with L‐cysteine methyl ester yields the bicyclic thiazolidinlactam 3 as a single diastereoisomer with the new bridgehead stereocenter in the (S) configuration. Regioselective activation of the α‐hydroxy group leads to the triflate 4 without requiring protecting groups on the residual hydroxy groups. Subsequent azide exchange, reduction, and Boc protection, yields the epimeric dipeptide mimetics 6 and 7. Compound 3 forms the single acetonide 9, which permits the regioselective alkylation of the γ‐hydroxy group of the bicyclic framework. Subsequent deprotection and exchange of the α‐hydroxy functionality against a Boc‐protected amino group (13) demonstrates the regioselective side‐chain modification of bicyclic dipeptides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)