Glycono-1,3-lactams, Xylo Series: Stereoselective Access by [2+2] Cycloaddition, Exploratory Transformations, and Discovery of a New, Highly Selective Inhibitor of Glucoamylases

Bernd Krämer; Thomas Franz; Sylviane Picasso; Petra Pruschek; Volker Jäger

doi:10.1055/s-1997-759

Synlett 1997; 1997(3): 295-297
DOI: 10.1055/s-1997-759

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Glycono-1,3-lactams, Xylo Series: Stereoselective Access by [2+2] Cycloaddition, Exploratory Transformations, and Discovery of a New, Highly Selective Inhibitor of Glucoamylases

Bernd Krämer¹ , Thomas Franz¹ , Sylviane Picasso¹ , Petra Pruschek² , Volker Jäger³

¹Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
²Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany; Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
³Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany, Fax: Int. code +711/685 4321; E-mail: jager.ioc@po.uni-stuttgart.de

Abstract

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[2+2] Cycloaddition of chiral imines 4-7, derived from 2-O-benzylglyceraldehyde, with α-alkoxyketenes 1-3 furnished 3-amino-3-deoxy-glycono-1,3-lactams 8-15 (50-78%) with 2,3-cis configuration in diastereomeric ratios of 87:13 to >95:5. From these O,N-deprotected β-lactams 16-18 were prepared. Reduction of the xylono-1,3-lactam 18 using monochloroalane (ClAlH₂) produced the corresponding azetidine 19, while reduction of 14 with LiAlH₄ have the aminotetrol derivative 20. Treatment of the β-lactam triol 21 with NaIO₄ led to the 3,4-dihdro-2H-1,4-oxazine-3-one 22, via cleavage of the C2-C3 bond and recyclization. The 1,3-imino-xylitol 19 exhibited highly selective inhibition of the two gluco-amylases tested (IC₅₀ values of 31 and 4 (M).

α-alkoxyimine - β-lactam - 1,3-imino-glycitol - amino polyol - glycosidase inhibition

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