Total Synthesis of (+)-Euphorikanin A via an Atropospecific Cascade.

A total synthesis of the ingenane-derived diterpenoid (+)-euphorikanin A is described. Key to the strategy is a stereocontrolled one-pot sequence consisting of transannular aldol addition reaction, hemiketal formation, and subsequent semipinacol rearrangement that efficiently leads to the complete euphorikanin skeleton. Atroposelective ring-closing olefin metathesis proved critical for the stereospecific cascade, leading to formation of a (Z)-bicyclo[7.4.1]tetradecenone core. An additional salient feature of the route is pyrolysis of a bis-methylxanthate to cleanly furnish the natural product.

Enantioselective Total Synthesis of (+)-Euphorikanin A.

We disclose the first total synthesis of (+)-euphorikanin A, an ingenane-derived natural product featuring an unprecedented 5/6/7/3-fused tetracyclic skeleton. Key to the approach is a SmI2-mediated ketyl-enoate reaction that leads to the formation of two rings in a single step. The polarity-reversed cyclization proceeds in excellent yield and high diastereoselectivity. Access to ring B is effected late in the synthesis by implementation of a number of chemoselective transformations, including in situ generation of a vinyl lithium species and subsequent intramolecular attack onto an α-ketolactone.

Synthesis of Alfaprostol and PGF2α through 1,4-Addition of an Alkyne to an Enal Intermediate as the Key Step.

The veterinary drug Alfaprostol and prostaglandin PGF2α have been synthesized in just nine steps. The strategy involved the conjugate addition of an alkyne to a bicyclic enal, available in three steps by a proline-catalyzed aldol reaction of succinaldehyde. In the case of Alfaprostol, this resulted in the shortest synthesis reported to date. For PGF2α, this approach improved our previous route by making the 1,4-addition and ozonolysis more operationally simple.