Synthesis of (–)-Scabrolide A

Key words

(–)-scabrolide A - norcembranoid diterpenoid - Diels–Alder reaction - hydrosilylation - [2+2] cycloaddition - Tamao–Fleming oxidation - Grieco elimination - oxidative fragmentation/ elimination

Significance

Stoltz and co-workers report the first total synthesis of (–)-scabrolide A, a norcem­branoid diterpenoid isolated from soft coral Sinularia scabra. The target compound inhibits production of IL-6 and IL-12 and therefore holds promise as anti-inflammatory agent. The fused [5,6,7]-scaffold features six stereogenic centers.

Comment

The authors employ a convergent route which couples two fragments derived from the chiral pool by esterification. Diels–Alder reaction and [2+2] cycloaddition generate a [5,6,4,5]-scaffold which is then elaborated to the target compound by an oxidative fragmentation/elimination.