Free-radical mediated synthesis of enantiomerically pure, highly functionalized inositols from carbohydrates

• Published in: Carbohydrate research 2001-06, Vol.332 (4), p.341-349
• Main Authors: Marco-Contelles, José, Pozuelo, Carmen, de Opazo, Elsa
• Format: Article
• Language: English
• Subjects: Carbocyclization; Carbohydrates; Free Radicals; Gas Chromatography-Mass Spectrometry; Indicators and Reagents; Inositol - analogs & derivatives; Inositol - chemical synthesis; Inositol - chemistry; Inositols; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Optical Rotation; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism; Tributyltin hydride
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(01)00116-1

We report the synthesis, free-radical cyclization of precursors 1,2,7-trideoxy-7-iodo-3,4:5,6-di- O-isopropylidene- d- gluco-hept-1-enitol ( 1), methyl 7- O-acetyl-6- O-benzyl-8-bromo-2,3,8-trideoxy-4,5- O-isopropylidene- d- gluco-oct-2-enonate ( 2) and 5- O-acetyl-4- O-benzyl-6-bromo-6-deoxy-2,3- O-isopropylidene- d-glucose- O-benzyloxime ( 3), readily prepared from d-glucose, and some selected transformations of the carbocycles obtained from these intermediates. In compound 1 we have installed a terminal double bond and an iodide as radical acceptor and leaving group, respectively. Compounds 2 and 3 are ε-bromo aldehydes substituted with α,β-unsaturated ester and oxime ether functions as radical traps, respectively. The tributyltin hydride mediated ring closure of these radical precursors have afforded a series of interesting, diverse and highly functionalized carbocycles which can be considered useful building blocks for the synthesis of branched-chain cyclitols, aminocyclitols and aminoconduritols. In these processes, a good chemical yield and high stereoselectivity has been found in the newly formed stereocenters. Particularly interesting has been the finding that the stereochemical outcome of the free-radical cyclization is independent of the ratio of isomers ( E or Z) in oxime ether 3. These results show the power and the state of art of this strategy for the stereocontrolled synthesis of enantiomerically pure inositols from carbohydrates. Graphic