Total Synthesis of (–)-Rauvomine B

Key words

(–)-rauvomine B - sarpagine indole alkaloids - enantiospecific allylation - Pictet–Spengler reaction - Ohira–Bestmann homologation - azide dipolar cycloaddition - intramolecular cyclopropanation

Significance

Smith, Chen, and co-workers report the first total synthesis of (–)-rauvomine B, a monoterpene indole alkaloid belonging to the sarpagine class. The natural product features an unusual bridging cyclopropane motif embedded in an ­indoloquinolizidine unit. Key to the synthesis is the construction of a triazole via azide dipolar cycloaddition, which serves as a carbene precursor for the intramolecular cyclopropanation.

Comment

The synthesis commenced with the stereospecific allylation of tryptophan methyl ester A to secondary amine C. Compound C was engaged in a Pictet–Spengler reaction with aldehyde D to afford alkyl selenide E. Oxidation and elimination of E returned diene F, which was subjected to HG II catalyst, delivering the indoloquinolizidine in H. Conversion of the methyl ester into H to the key triazole L set the stage for the intramolecular cyclopropanation. ­Under Rh(II) catalysis, L formed the putative carbene that cleanly returned the full core of (–)-rauvomine B. Boc deprotection mediated by TFA completed the synthesis.

Publication History

Article published online:
13 September 2024