Convergent synthesis of the E'FGH ring fragment of ciguatoxin 1B via an acetylene cobalt complex strategy.

Abstract

A convergent synthesis of the E'FGH ring fragment 28 of ciguatoxin 1B, a principal toxin causing widespread seafood poisonings "ciguatera", has been accomplished through (i) coupling between the E' ring-acetylide 9 and the H ring-aldehyde 20, (ii) stereoselective F ring cyclization via an acetylene cobalt complex, (iii) conversion to a carbonyl function under high-pressure hydrogenation, and (iv) reductive hydroxyketone cyclization to construct the G ring. In the (1)H NMR analysis of 28 at room temperature, a considerable broadening phenomenon was observed due to the slow conformational changes of the FG ring, as reported for natural ciguatoxin 1B. When measured in pyridine at -20 degrees C, the spectra of 28 exhibited a 3.5:1 mixture of two conformational isomers (UP and DOWN conformers).