Synthesis of Endothiopeptides and Their Cyclization to 1,3-Thiazol-5(4H)-imines

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-Ψ(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 (Ala^t) 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.