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In order to gain access to 3-propoxy-β-carboline hydrochloride (3-PBC·HCl) (1·HCl), and β-carboline-3-carboxylate-t-butyl ester (βCCt) (2), potential clinical agents active against alcohol self-administration, a two-step route was developed. This process involves a palladium catalyzed Buchwald-Hartwig coupling and an intramolecular Heck reaction. This two-step route provides rapid access to multigram quantities of 3-PBC (1) and βCCt (2), as well as analogs for studies of alcohol self-administration. The overall yield of 3-PBC (1) was improved from 8 % to 50 % in this route.

A highly enantio- and diastereoselective strategy to access any member of the sarpagine/macroline family of oxindole alkaloids via internal asymmetric induction was developed from readily available D-(+)-tryptophan. At the center of this approach was the diastereospecific generation of the spiro[pyrrolidine-3,3’-oxindole] moiety at an early stage via a tert-butyl hypochlorite-promoted oxidative rearrangement of a chiral tetrahydro-β-carboline derivative. This key branching point determined the spatial configuration at the C-7 spiro center to be entirely 7R or 7S. Other key stereospecific processes were the asymmetric Pictet-Spengler reaction and Dieckmann cyclization, which were scalable to the 600 gram and 150 gram levels, respectively. Execution of this approach resulted in first enantiospecific total synthesis of (+)-isoalstonisine and (−)-macrogentine from the chitosenine series (7R), as well as (+)-alstonisine, (+)-alstofoline, (−)-alstonoxine A and (+)-Na-demethylalstonisine from the alstonisine series (7S).

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