Synthesis of C-17-functionalized spongiane diterpenes:: Diastereoselective synthesis of (-)-spongian-16-oxo-17-al, (-)-acetyldendrillol-1, and (-)-aplyroseol-14

The diastereoselective synthesis of spongiane diterpenes (-)-spongian-16-oxo-17-al 2, (-)-acetyl-dendrillol-1 15, and (-)-aplyroseol-14 16 has been completed efficiently via the common intermediate 14. Compound 14 was prepared in five synthetic steps from (+)-podocarp-8(14)-en-13-one 13, easily available from commercial H-abietic acid. The key steps in the syntheses were a regioselective reduction of a 1,4-dialdehyde unit, a one-pot acetalization-acetylation, and a translactonization. The synthesis of 15 and 16 has led us to a revision of the configuration at C-17 for natural (-)acetyldendrillol-1 and a structural reassignment for aplyroseol-14. Thus, aplyroseol-14 16 presents an unprecedented delta-lactone-based structure for spongiane-type diterpenoids. A theoretical study including a series of ab initio calculations for the mechanism involved in the conversion of ester 22 into natural product 2 has also been carried out.