Efficient synthesis of methyl (S)-4-(1-methylpyrrolidin-2-YL)-3-oxobutanoate as the key intermediate for tropane alkaloid biosynthesis with optically acitve form

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 amino alcohol, which were then followed by Swern oxidation, Wittig reaction and decarboxylative condensation. At the last step, N-methylamino 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 obvious 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
Pages (from-to)604-613
Number of pages10
JournalHeterocycles
Volume99
Issue number1
DOIs
StatePublished - 2019

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