Glycosidase inhibitors: Synthesis of enantiomerically pure aza-sugars fromSchiff base amino esters via tandem reduction-alkenylation and osmylation

Citation
R. Polt et al., Glycosidase inhibitors: Synthesis of enantiomerically pure aza-sugars fromSchiff base amino esters via tandem reduction-alkenylation and osmylation, J ORG CHEM, 64(17), 1999, pp. 6147-6158
Citations number
123
Categorie Soggetti
Chemistry & Analysis","Organic Chemistry/Polymer Science
Journal title
JOURNAL OF ORGANIC CHEMISTRY
ISSN journal
00223263 → ACNP
Volume
64
Issue
17
Year of publication
1999
Pages
6147 - 6158
Database
ISI
SICI code
0022-3263(19990820)64:17<6147:GISOEP>2.0.ZU;2-#
Abstract
`Nitrogen-in-the-ring "aza-sugars" have been synthesized in enantiomericall y pure form from the amino acid L-alanine in excellent overall yield. The O 'Donnell's Schiff base of L-alanine methyl eater 9a was converted to ate-su gar L-fuco-1-deoxy-nojirimycin, 18, and to the epimer L-gulo-1-deoxy-nojiri mycin, 20, in eight steps. The overall yields were 20 and 29%, respectively . The methodology for the efficient generation of silyl- and benzyl-protect ed (E)-3-lithio-2-propen-1-ols, and the use of these alkenyllithiums with i Bu(5)Al(2)H as nucleophiles in the three-selective tandem reduction-alkenyl ation of the Schiff base esters is described. Osmium-catalyzed cis-oxygenat ion of the resulting olefin products was selective for the galacto (fuco) a mino polyols in all cases for the acyclic olefins, and was gulo-selective f or the cyclic D-4,5-dihydropyridine pivalate, 17c. TEMPO-NaOCl was selectiv e for oxidation of the primary position of the acyclic Schiff bases, and al lowed for minimal protection/deprotection of the intermediates. The resulti ng N-benzhydryl heterocycles were easily deprotected with H-2-Pd at atmosph eric pressure.