A unified approach to highly functionalized clovane-type terpenoids: enantiocontrolled total synthesis of rumphellclovane E and sarinfacetamides A and B

Abstract

This study presents an enantioselective collective total synthesis of the highly functionalized clovane-type terpenoids rumphellclovane E (4) and, sarinfacetamides A (5) and B (6). An efficient enantio-controlled, second-generation route to an originally designed versatile intermediate (12/ent-12) enables the collective synthesis, including the first total synthesis of sarinfacetamides A (5) and B (6). The rapid assembly of the bicyclo[3.3.1]nonane core via a domino Michael–aldol reaction employing a novel acrolein surrogate under basic conditions enabled access to this key intermediate, requiring only five steps from (+) or (−)-dihydrocarvone (18/ent-18). We further demonstrated the versatility of this strategy through the synthesis of a structural analogue containing a furan moiety. Given the diverse biosynthetic origins of clovanes, which arise from caryophyllene or xeniaphyllane terpenoids, this synthetic strategy may prove applicable to a broader range of clovane-type terpenoids.