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 (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.
Aib-Pro-OMe (9) [4], an endothio derivative of the apolar segment 1 ± 10 of the zervamicin IIA-analogue 8 [29] (Fig. ).
In the present work, we describe our further investigations in preparing other endothio derivatives of 8. We intended to synthesize endothiodecapeptides 10 ± 12 to show, on the one hand, the usefulness of our methodology and, on the other hand, to solve their crystal structures, with the aim of further understanding the influence of the