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2-Nitroglycals: versatile intermediates for efficient and highly stereoselective base-catalyzed glycoside bond formations

Nature Protocols volume 3, pages 114–121 (2008)Cite this article

Abstract

This protocol describes the O-glycosyl trichloroacetimidate-based glycosylation of protected galactal 1 as acceptor under Sn(OTf)2 catalysis to give disaccharide 4. Nitration of the galactal moiety using nitric acid–acetic acid as nitrating agent followed by base-promoted acetic acid elimination affords the 2-nitro derivative 6 in a one-pot procedure. These types of intermediates can be used in the stereoselective synthesis of glycosides via Michael-type addition of alcohols as nucleophiles to 2-nitroglycals. Here, the base-catalyzed α-selective addition of N-Boc-protected Ser and Thr esters (7a, b) is described, which leads stereoselectively to adducts 8a, b. Transformation into the corresponding 2a-acetylamino derivates 9a, b provides versatile mucin core 1 building blocks (the total time for synthesizing 9a, b starting from 1 to 2 is typically 7 d with an overall yield of 18–25%). Also various other types of nucleophiles are amenable to this Michael-type addition 2-nitroglycals.

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Figure 1
Figure 2: Michael-type addition of O-, N-, C-, S- and P-nucleophiles to 2-nitrogalactal as donor.
Figure 3

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  1. Fachbereich Chemie, Universität Konstanz, Fach M 725, Konstanz, D-78457, Germany

    B Gopal Reddy & Richard R Schmidt

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Correspondence to Richard R Schmidt.

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Reddy, B., Schmidt, R. 2-Nitroglycals: versatile intermediates for efficient and highly stereoselective base-catalyzed glycoside bond formations. Nat Protoc 3, 114–121 (2008). https://doi.org/10.1038/nprot.2007.495

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