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

Abstract

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