| Abstract
| - The marine-derived halipeptins A (1a) and D (1d) and their analogues 3a, 3d and 4a, 4d weresynthesized starting from building blocks 10, 13, 14a or 14d, 15, and 16. The first strategy for assemblingthe building blocks, involving a macrolactamization reaction to form the 16-membered ring hydroxy thioamide52d as a precursor, furnished the epi-isoleucine analogue (4d) of halipeptin D, whereas a second approachinvolving thiazoline formation prior to macrolactamization led to a mixture of halipeptins A (1a) and D (1d)and their analogues 3a, 3d (epimers at the indicated site) and 4a, 4d (epimers at the indicated site). Thesame route starting with d-Ala resulted in the exclusive formation of the epimeric halipeptin D analogue3d. The synthesized halipeptins, together with the previously constructed oxazoline analogues 5d and 6d,were subjected to biological evaluation revealing anti-inflammatory properties for 1a, 1d, and 6d whilebeing noncytotoxic against human colon cancer cells (HCT-116).
|
