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Synfacts 2007(3): 0324-0324  
DOI: 10.1055/s-2007-968232
Organo- and Biocatalysis
© Georg Thieme Verlag Stuttgart · New York

Remote Desymmetrization: Peptide versus Enzyme Catalysis

Contributor(s): Benjamin List, Corinna Reisinger
C. A. Lewis, A. Chiu, M. Kubryk, J. Balsells, D. Pollard, C. K. Esser, J. Murry, R. A. Reamer, K. B. Hansen*, S. J. Miller*
Yale University, New Haven, Boston College, Chestnut Hill and Merck Research Laboratories, Rahway, USA
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Publication History

Publication Date:
20 February 2007 (online)

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Significance

A catalytic protocol for the unprecedented remote asymmetric desymmetrization of bis(phenol) 1 via peptide-catalyzed monoacetylation has been developed. Since the desired site of functionalization is >5.7 Å from the ‘prochiral’ stereogenic center and the enantiotopic oxygen ­atoms are separated by a near-nanometer span, bis(phenol) 1 represents a particulary challenging substrate. After an examination of libraries of hexa­meric peptides 3, whose residue pattern was chosen as a mirror image of the alternating aromatic-aliphatic-aromatic nature of substrate 1, and followed by a truncation study of lead catalyst 4, tetramer 5 was identified as the best catalyst, delivering monoacetylated product 2 in 80% yield and with an er of 97.5:2.5.