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Dramatic effect of modified boranes in diastereoselective reduction of chiral cyclic α-ketophosphinates†
Damien Filippini,Severine Loiseau,Norbert Bakalara,Arie Van der Lee,Jean-Noël Volle,David Virieux,Jean-Luc Pirat
RSC Advances Pub Date : 12/15/2011 00:00:00 , DOI:10.1039/C2RA00799A
Abstract

Phostines have been recently described as compounds having antiproliferative properties. Original synthesis of this new class of phosphinic analogs of pyranoses led to a mixture of four diastereomers 3–6 with unequal bioactivities. The most active compound 4 was originally obtained from a mixture of these four diastereomers by selective precipitation, giving firstly two diastereomers 3 and 4, epimers at the carbon atom. From the latter mixture 3 and 4, oxidation with Dess–Martin reagent afforded corresponding α-ketophosphinate 7, which by diastereoselective reduction using a chiral agent based on sodium borohydride and L-proline, gave preferentially the active diastereomer 4. In addition, use of a multivalent cation also increased the diastereoselectivity favourably.

Graphical abstract: Dramatic effect of modified boranes in diastereoselective reduction of chiral cyclic α-ketophosphinates
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