Dehydromicrosclerodermin†B and Microsclerodermin†J: Total Synthesis and Structural Revision.

The total synthesis of dehydromicrosclerodermin B and microsclerodermin J is described. Efficient approaches to the unusual amino acids in the target molecules were developed on the basis of a Negishi coupling (for Trp-2-CO2 H) and Blaise reaction (for Pyrr). An incorrect assignment of the pyrrolidinone stereochemistry of both compounds was confirmed by synthesizing epimers of the proposed structures. The spectroscopic data of these epimers were in complete agreement with those for the naturally derived material.

Directing group enhanced carbonylative ring expansions of amino-substituted cyclopropanes: rhodium-catalyzed multicomponent synthesis of N-heterobicyclic enones.

Aminocyclopropanes equipped with suitable N-directing groups undergo efficient and regioselective Rh-catalyzed carbonylative C-C bond activation. Trapping of the resultant metallacycles with tethered alkynes provides an atom-economic entry to diverse N-heterobicyclic enones. These studies provide a blueprint for myriad N-heterocyclic methodologies.

Tethered aminohydroxylation: synthesis of the ß-amino acid of microsclerodermins A and B.

The utility of the tethered aminohydroxylation (TA) has been demonstrated by synthesis of the complex ß-amino acid residue of microsclerodermins A and B. The TA provided a regio- and stereoselective functionalization of a complex homoallylic alcohol. The route includes late-stage introduction of the aliphatic side chain via a cuprate addition and cross metathesis, a tactic designed to render the synthesis applicable to other microsclerodermins.