Rapid Synthesis of anti-1,3-Diamino-4-phenylbutan-2-ol Building Blocks via a Three-Component Oxyhomologation and a Two-Component Reducing System

N -substituted derivatives of anti-(2R,3S)-1,3-diamino-4-phenylbutan-2-ol are important building blocks for the synthesis of therapeutically important molecules. We describe a simple protocol that allows transformation of N,N-dibenzyl-L-phenylalaninal into such compounds in only two steps. The first...

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Published in:ChemistryOpen (Weinheim) 2024-10, p.e202400279
Main Authors: Cabua, Maria Chiara, He, Xuefeng, Secci, Francesco, Deloisy, Sandrine, Aitken, David J
Format: Article
Language:English
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Summary:N -substituted derivatives of anti-(2R,3S)-1,3-diamino-4-phenylbutan-2-ol are important building blocks for the synthesis of therapeutically important molecules. We describe a simple protocol that allows transformation of N,N-dibenzyl-L-phenylalaninal into such compounds in only two steps. The first step is a fully stereoselective three-component MAC (Masked Acyl Cyanide) oxyhomologation reaction implicating different amines to give a panel of ten N,N-dibenzyl-O-tert-butyldimethylsilyl-protected anti-(2S,3S)-allophenylnorstatin amides. The second step is a carbonyl-activated hydride deprotection/reduction protocol using trimethylsilyl chloride and lithium aluminium hydride; the one-pot two-component system is more efficient than the alternative approach of isolating the deprotected amide intermediate before reduction.
ISSN:2191-1363
2191-1363
DOI:10.1002/open.202400279