title: 4-C-Me-DAB and 4-C-Me-LAB - enantiomeric alkyl-branched pyrrolidine iminosugars - are specific and potent α-glucosidase inhibitors; acetone as the sole protecting group.
abstract: The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pK(a) of the salt around 8.4] is discussed and illustrates the need for care in analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase K(i) 0.89 μM, IC(50) 0.41 μM) is a competitive - whereas 4-C-Me-LAB (for rat intestinal sucrase K(i) 0.95 μM, IC(50) 0.66 μM) is a non-competitive - specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB, and isoDAB - but not isoLAB - is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Filipa P
authors.initials: FP
authors.lastname: da Cruz
authors.forename: Scott
authors.initials: S
authors.lastname: Newberry
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Jenkinson
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wormald
authors.forename: Terry D
authors.initials: TD
authors.lastname: Butters
authors.forename: Dominic S
authors.initials: DS
authors.lastname: Alonzi
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Frederic
authors.initials: F
authors.lastname: Becq
authors.forename: Caroline
authors.initials: C
authors.lastname: Norez
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nash
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: George W J
authors.initials: GW
authors.lastname: Fleet