A NEW SYNTHETIC APPROACH TO THE CARBOCYCLIC CORE OF CYCLOPENTANE-TYPEGLYCOSIDASE INHIBITORS - ASYMMETRIC-SYNTHESIS OF AMINOCYCLOPENTITOLS VIA FREE-RADICAL CYCLOISOMERIZATION OF ENANTIOMERICALLY PURE ALKYNE-TETHERED OXIME ETHERS DERIVED FROM CARBOHYDRATES

The synthesis of compounds 6-8, derived from 2,3:5,6-bis-O-isopropylid ene-D-mannofuranose (3), and the preparation of products 16 and 17, ob tained from 2,3-O-isopropylidene-D-ribose (13) is reported. The first free radical cyclization of enantiomerically pure alkyne-tethered oxim e ethers derived from carbohydrates (6, 8, 16, and 17) is described. T hese radical precursors have been submitted to cyclization with tribut yl or triphenyltin hydride plus triethylborane to yield, after ring cl osure, the aminocyclopentitols 9-12 and 18-20, respectively. These car bocycles have been obtained as mixtures of Z and E vinyltin isomers, b ut with excellent diastereoselection at the new stereocenter formed du ring the ring closure. After protodestannylation, only one diastereois omer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established b y detailed H-1 NMR analysis. The specific transformation of compound 1 9 (or 20) into aminocyclitol 24 is described. Compound 24 is an analog ue of the aminocyclopentitol moiety of trehazolin (1a), a known and po werful glycosidase inhibitor of trehalase. From these results, we can conclude that a new method for the asymmetric synthesis of aminocyclit ols of biological interest is now available.