C-24 Stereochemistry of Marine Sterols: (22E)-24-(Isopropenyl)-22-dehydrocholesterol and 24-Isopropenylcholesterol (original) (raw)

2006, CHEMICAL & PHARMACEUTICAL BULLETIN

We have recently isolated a series of multiply alkylated sterols, including a new C 31-sterol, ophirasterol [(22E)-24-(1buten-2-yl)cholesta-5,22-dien-3b-ol], from the Caribbean sponge, Topsentia ophiraphidites. 1) Among these sterols, the C-24 configurations of ophirasterol, 1) (22E)-24-ethyl-24methyl-22-dehydrocholesterol and 24-ethyl-24-methylcholesterol were determined to be R, R and S, respectively, through synthetic and X-ray studies. 2) We have now investigated the C-24 configuration of (22E,24x)-24-isopropenyl-22-dehydrocholesterol 1 (Fig. 1). The isolation of 1 was reported also from other marine sources and a terrestrial plant (vide infra). NMR comparison of the natural 1 and synthetic, stereodefined (24R)-and (24S)-samples led to the stereochemical assignment of 1. Stereochemically defined (24R)and (24S)-24-isopropenylcholesterols (2a, b) were also synthesized and the C-24 configurations of the samples of (24x)-24-isopropenylcholesterol 2 reported previously are discussed. (24R)-and (24S)-(22E)-D 22-24-isopropenylcholesterols (1a, b) and (24S)-and (24R)-24-isopropenylcholesterols (2a, b) were synthesized stereoselectively in a route involving orthoester Claisen rearrangement (Chart 1). The known starting materials, (22R)-and (22S)-allylic alcohols 3a and 3b, 3) were used in our recent synthesis of ophirasterol and its C-24 epimer. 1) Exposure of 3a to a condition of orthoester Claisen rearrangement (triethyl orthopropionate and a catalytic amount of propionic acid in refluxing xylene) gave the (24R)-rearranged ester 4a as a ca. 1 : 1 mixture at the C-28 position, as revealed by 13 C-NMR analysis of 4a. The config