Total Syntheses of (±)-Agelasimine-A, (±)-Agelasimine-B, and (±)-Purino-diterpene and the Structure of Diacetylagelasimine-A

Abstract

A full account is given of the first racemic syntheses of agelasimine-A (1a) and agelasimine-B (2a), adenine-related bicyclic diterpenoids isolated from the marine sponge Agelas mauritiana. Central synthetic features include a highly stereoselective construction of the diol (±)-13, a key intermediate for their common diterpene portion, and regioselective alkylations on the adenine portions. The palladium-catalyzed cross-coupling reaction of the 9-alkyl-9-BBN derivative (±)-17 with the 1-alkenyl triflate or halides 15a−c was examined in detail as a preliminary to the preparation of the precursor (±)-10. The above syntheses of (±)-1a and (±)-2a have unequivocally confirmed the correctness of the structures and relative stereochemistries proposed for agelasimine-A and -B. The reaction of (±)-1a with acetic anhydride in pyridine afforded the monocyclic imidazole derivative (±)-25a, which was found to correspond to “diacetylagelasimine-A”, initially assigned the purine form 26a. A similar acetylation of (±)-2a led to the racemic synthesis of purino-diterpene (3a), an artifact separated from the acetylated mixture of the crude extract of A. mauritiana.