Total Synthesis of Altohyrtin A (Spongistatin 1): Part 2

Abstract

The most active compound of the extraordinarily cytotoxic spongipyrans, spongistatin 1, isolated from marine sponges, appeared to be identical to altohyrtin A. The total synthesis of this macrolide has now firmly established the relative and absolute stereochemistry proposed by Kitagawa (see picture below), and has also verified that altohyrtin A and spongistatin 1 are identical.

Role of the Nozaki–Hiyama–Takai–Kishi Reaction in the Synthesis of Natural Products

“…After trying different transition metals, they discovered that NiCl 2 was the reason behind this beneficial catalytic effect. Right after this serendipitous discovery, Kishi’s group exploited the new methodology in several new total syntheses of relevant natural products, such as (+)-ophiobolin C, halichondrin B and norhalichondrin, altohyrtin A, , and pinnatoxin A …”

Recherche de substances naturelles à activité thérapeutique (2)

“…La configuration absolue de la spongistatine 1, initialement déduite par G.R. Pettit, est confirmée en 1998 par Y. Kishi après synthèse totale [37,38]. En 2005, M. Ball réduit le nombre d'étapes de la synthèse totale de la spongistatine 1 de 65 à 46 [39], et, en 2008, le protocole de synthèse totale établi par A.B.…”