Stereodivergent and enantioselective total syntheses of isochaetominines A–C and four pairs of isochaetominine C enantiomers: a six-step approach

The first enantioselective and stereodivergent total syntheses of (−)-isochaetominines A–C and all eight 2,3-cis-stereoisomers of (−)-isochaetominine C, including the natural (+)-14-epi-isochaetominine C, and the proposed structures of (−)-pseudofischerine (2) and (−)-aniquinazoline D (3), have been achieved. The stereodivergent approach relies on the DMDO-initiated divergent tandem reaction to give a separable mixture of two products, a monocyclization product and a diastereomer of isochaetominine C (or a homologue) as a result of double cyclization. An epimerization-free two-step protocol has been developed for the highly diastereoselective transformation of the former product into an isochaetominine-type compound with characteristic 3,14-cis-stereochemistry. As a result of our synthetic efforts, the structures of the natural (−)-pseudofischerine and (−)-aniquinazoline D have been revised both as (−)-isochaetominine C (6).