Synthesis of endothiopeptides and their cyclization to 1,3-thiazol-5(4H)-imines

Further investigations of the synthesis of endothio analogues of the segmen t 1-10 (8) of an apolar analogon of zervamicin IIA are described. The endot hiodecapeptide Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Psi(CS)-Pro-OMe (10) has been prepared in good yield by our novel methodology. On the other han d, all attempts to prepare endothio analogues of 8 with the thioamide group at position 3 (Ala') gave not the expected linear endothiopeptides but led to epimerized 1,3-thiazol-5(4H)-imine derivatives as the main products. Th e mixture of epimers of the thiazolimines 27, 30, and 31 have been separate d by means of preparative HPLC, and their structures have been established by 2D-NMR experiments.