Alkaloid and steroid chemistry of Percy L. Julian

CMA 4

Ned Heindel, ndh0@lehigh.edu, Department of Chemistry, Lehigh University, 6 East Packer Avenue, Bethlehem, PA 18015
He may not have synthesized the first alkaloid or even prepared the first synthetic medicinal substance, but Percy Julian's 1935 total synthesis of the potent cholinesterase inhibitor physostigmine was a global trailblazing event. Carried out in an ill equipped undergraduate institution, with novice student co-researchers, in refutation of the work of a world-renowned British professor, and under enormous time constraints, the eight-step synthesis was a creative tour de force. Regiospecific placement of three pendant methyl moieties established once and for all their location around the molecule's periphery. Use of a benzylidene to control mono-alkylation and a reductive cyclization to generate a pyrroloindole constituted impressive and creative chemistry then and now. As a process suitable for use at manufacturing level, Julian designed in an atom economy in his multistep route that would impress a serious present-day student of process R&D. Later in his career Julian applied similar principles to sterol-to-steroid conversions which formed the basis of a significant revenue stream for the Glidden Company and Julian Laboratories.