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Highly Regioselective Oxirane Ring‐Opening of a Versatile Epoxypyrrolidine Precursor of New Imino‐Sugar‐Based Sphingolipid Mimics
Author(s) -
Rives Arnaud,
Génisson Yves,
Faugeroux Vanessa,
Zedde Chantal,
Lepetit Christine,
Chauvin Remi,
Saffon Nathalie,
AndrieuAbadie Nathalie,
Colié Sandra,
Levade Thierry,
Baltas Michel
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900100
Subject(s) - regioselectivity , chemistry , heteroatom , steric effects , sphingolipid , ring (chemistry) , substituent , nucleophile , stereochemistry , organic chemistry , biochemistry , catalysis
An in‐depth study of the oxirane ring‐opening reaction of a pivotal epoxypyrrolidine is reported. The introduction of various carbon‐ and heteroatom‐centered nucleophiles at C4 has been achieved with high regiocontrol. The structures of the major products were assigned on the basis on an X‐ray crystallographic study of six examples. A mechanistic study carried out at the B3LYP/6‐31G** level of theory suggested that the steric control of the vinyl substituent was responsible for the regioselectivity. Finally, this approach was used to design and prepare imino‐sugar‐based sphingolipid mimics. A highly cytotoxic C ‐octylpyrrolidine is described. This compound was shown to interfere with the metabolism of sphingolipids in murine melanoma cells, notably in inhibiting the production of glucosylceramide. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)