UC Berkeley

Part I: Altemicidin and related Streptomyces-derived monoterpene alkaloids possess, highly-polar, dense azaindane cores as well as potent cytotoxic and tRNA synthetase inhibitory properties. The congested alpha-amino acid motif decorating their presumed ten-carbon iridoid-like core structure has proven both a synthetic challenge and biosynthetic mystery. This work relates the synthetic process which culminated in a distinct and concise synthesis of altemicidin from simple chemical feedstocks. Key chemical findings include the exploitation of dearomative pyridinium addition and dipolar cycloaddition sequence to stereospecifically install the quaternary amine moiety, and a chemoselective molybdenum-mediated double reduction to establish the fully functionalized azaindane nucleus with minimal redox manipulations.Part II: Synthetic efforts to the tropone-containing cephalotaxane natural product, harringtonolide, are disclosed. The synthetic approach involves construction of the 7-6-5-6 ring system through a Diels-Alder-Barbier coupling sequence followed by ring-closing metathesis. Subsequent advancement efforts via oxidation and stereocenter epimerization are reported.