Free-radical mediated synthesis of enantiomerically pure, highly functionalized inositols from carbohydrates.
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 epsilon-bromo aldehydes substituted with alpha,beta-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.
Marco-Contelles
J
J
Laboratorio de Radicales Libres, Instituto de Química Organica General (CSIC), C/ Juan de la Cierva 3, E-28006, Madrid, Spain. iqoc21@iqog.csic.es
Pozuelo
C
C
de Opazo
E
E
D002241:Carbohydrates; D005609:Free Radicals; D008401:Gas Chromatography-Mass Spectrometry; D007202:Indicators and Reagents; D007294:Inositol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009904:Optical Rotation; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D002241:Carbohydrates; D005609:Free Radicals; D007202:Indicators and Reagents; D007294:Inositol