General approach to halogenated tetrahydrofuran natural products from red algae of the genus Laurencia. Total synthesis of (.+-.)-trans-kumausyne and demonstration of an asymmetric synthesis strategy

Abstract

A general strategy for the synthesis of C 15 halogenated tetrahydrofuranoid lipids from red algae of the genus Laurencia has been developed. The central step is the convenient formation of hydrobenzofuranone (±)-5 on a large scale, and with complete stereocontrol, from the acid-catalyzed condensation of 1-vinylcyclopentanediol (3) and α-(benzyloxy) acetaldehyde (Scheme II). Starting with the chiral, nonracemic (1S,2R)-diol 3, hydrobenzofuranone (-)-5 is also available in good enantiomeric purity (Scheme V). The total synthesis of (±)-trans-kumausyne from rac-5 is accomplished in 13 steps and >5% overall yield