6-Deoxyerythronolide B Synthase Thioesterase-Catalyzed Macrocyclization Is Highly Stereoselective
Organic Letters2012Vol. 14(9), pp. 2278–2281
Citations Over TimeTop 10% of 2012 papers
Abstract
Macrocyclic polyketide natural products are an indispensable source of therapeutic agents. The final stage of their biosynthesis, macrocyclization, is catalyzed regio- and stereoselectively by a thioesterase. A panel of substrates were synthesized to test their specificity for macrocyclization by the erythromycin polyketide synthase TE (DEBS TE) in vitro. It was shown that DEBS TE is highly stereospecific, successfully macrocyclizing a 14-member ring substrate with an R configured O-nucleophile, and highly regioselective, generating exclusively the 14-member lactone over the 12-member lactone.
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