Efficient synthesis of (S)-4-(1- methylpyrrolidin-2-yl)-3-oxobutanoate as the key intermediate for tropane alkaloid biosynthesis without racemization

Nanda Kumar Katakam, Cole Seifert, John D'Auria, Guigen Li

Research output: Other contribution

Abstract

Methyl (S)-4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate has been synthesized for enzymatic studies on cyclization enzymes during cocaine biosynthesis in Erythroxylum coca plants. During the present new synthesis, L-proline was first protected with Cbz group and reduced to chiral aminoalcohol, which were then followed by Swern oxidation, Witting reaction and decarboxylative condensation. At the last step, N-methyl amino acid precursor was treated with 1,1’-carbonyldiimidazole followed by reacting with methyl potassium malonate to give the 3-oxobutanoate in 54% overall yield. This new strategy has proven to avoid racemization of the L-proline chiral center during the synthesis. In addition, six of the eight synthesis steps were performed via GAP chemistry/technology without the use of column chromatography for purification.
Original languageEnglish
Volume99
DOIs
StatePublished - Jun 18 2018

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