Total syntheses of marine sponge metabolites. Part 3. Stereoselective total synthesis of (±)-12-deoxyscalaradial

Abstract

A highly efficient total synthesis of (±)-12-deoxyscalaradial (1d), a representative of the scalaradials from marine sponges, is described. (±)-Labda-8(20),13-dien-15-oic acid (3), chosen as the starting material, was transformed to the known tricyclic alcohol (4a) and the latter was oxidised with Swern's reagent to the aldehyde (4b). Isomerisation of compound (4b) with toluene-p-sulphonic acid in benzene afforded the conjugated aldehyde (5), which on Wittig reaction with methylenetriphenylphosphorane yielded the diene (6). On heating with dimethyl acetylenedicarboxylate the diene (6) afforded the Diels–Alder adduct (7a). Refluxing of compound (7a) with 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) gave the isomeric conjugated diester (8), which on hydrogenation over 10% Pd–C led to the desired trans-fused olefin diester (1e). Reduction of compound (1e) with lithium aluminium hydride, followed by Swern's oxidation, provided the desired dialdehyde (1d).

The synthesis of the trans-fused olefin diester (1e) from compound (7a), via an alternative five-step sequence of reactions, is also reported.