2,3,6-Tri-O-benzyl-D-myo-inositol, which is a key intermediate of D-inositol 1,4,5-triphosphate, was synthesized from D-glucose without performing any optical resolution by utilizing C2 symmetry. Laminitol and mytilitol were also synthesized from D-glucose via the same key intermediate, 1D-{1,3/2,4)-tetra-O-benzyl-2-Cmethyl-5-cyclohexene-1,2,3,4-tetrol.Since the discovery of the role of o-myo-inositol 1,4, 5-triphosphate (IP3, 1) as an intracellular second messenger for calcium mobilization,l) the biological interest in IP 3 has greatly increased. In order to explore the biochemical process, a simple, general, and efficient methodology for the chemical syntheses of 1 and its derivatives is required that will act as agonists in the phosphoinositide system. 2) The biological importance of other stereoisomers of inositol is less well established. 3 ) However, there are two known naturally-occurring Cmethyl inositols, both isolated from algae: (-)-laminitol (3) and mytilitol (4) (Chart 1). Compound 3 is especially interesting in that it has the myo-inositoltype configuration with a methyl group at C-4, and that it inhibits the growth of Neurospora crassa. 4 ) Syntheses of racemic laminitol from myo-inositol 5 ) and (-)-laminitol from toluene 6l have been reported. To date, however, for the syntheses of 1 and its derivatives, naturally occurring cyclitol derivatives, myo-inositol,7) quebrachitol,8) and quinic acid 9 ) have been mainly used as the starting materials. In general, optical resolution has been required in the case of using myo-inositol, which has a plane of symmetry. We now report on novel synthetic methods of optically active laminitol and mytilitol, as well as details concerning a communication10) about 2,3,6-tri-0-benzyl-o-myo-inositol (2) from o-glucose, respectively. (5) was prepared from o-glucose in 56% yield (3 steps) (Scheme 1). 6-Deoxyhex-5-enopyranoside derivative (6) was synthesized by the treatment of 5 with sodium iodide, tetrabutylammonium iodide, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and molecular sieves 4A in dimethyl sulfoxide (DMSO) at 90 DC (one-pot reaction, 63% yield). Detosylation of 6, followed by protection with a benzyl group, gave methyl 2-0-benzyl-6-deoxy-3,4-bis( 0-methoxymethyl)-Q-0-xylo-hex-5-enopyranoside (8) in 87% yield (2 steps). A Ferrier reaction of 8 gave a partially protected 2,3,4,5-tetrahydroxycyclohexanone derivative, which was treated with acetic anhydride in pyridine to give the corresponding enone derivative (9) in 77% yield (2 steps). The reduction of 9 with sodium tetrahydroborate--cerium (III) chloride in dichloromethane-ethanol (1: 2), followed by benzylation of the hydroxyl group gave the protected cyclohexenol derivative (10) in 89% yield (2 steps). Oxidation of 10, which has a C 2 symmetry axis, 11) with osmium tetraoxide gave a partially protected myo-inositol derivative (11) in 83% yield. The regioselective protection of the vicinal hydroxyl groups of 11 by using dibutyltin oxide and chloromethyl methyl ether, followed by benzylation of the remain...

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Cyclophellitol [lL-(1,2,4,6/3,5)-1 ,2-anhydro-6-(hydroxymethyl)-cyclohexane-1,2,3,4,5-pentol], a novel~-glucosidase inhibitor, has been synthesized from D-glucose via a branched-chain 6-deoxyhex-5-enopyranoside.Cyclophellitol is a novel~glucosidase inhibitor recently isolated from the culture filtrate of a mushroom, phellinus sp., and also a potent inhibitor of infection of human immunodeficiency virus (HIV).l) Total syntheses of cyclophellitol (1) from L-glucose,2) L-quebrachitol,3) and furan 4 ) were already reported. Recently, a new approach toward the methyl-branched cyclitols using palladium catalyst have been reported by Gero et al. 5 ) and also reported 6 ) by us the syntheses via the corresponding key intermediates, branched-chain 6-deoxyhex-5-enopyranosides, which were prepared from branched-chain hexopyranosides. Moreover, authors established a new approach for the syntheses of various functionalized branched-chain hexopyranosides by the use of dichloromethyllithium.7) On the basis of above knowledge, we report here a new approach for the synthesis of 1 starting from D-glucose.Our synthetic strategy of 1 from D-glucose is showed in scheme 1. The synthesis began with the preparation of methyl 3-0-benzoyl-4,6-0-benzylidene-a-D-arabino-hexopyranosid-2-ulose (2).8) (Scheme 2) Stereoselective introduction of dichloromethyl function?) to compound 2 gave methy14,6-0-benzylidene-2-CdicWoromethyl-a-D-glucopyranoside (3), of which structure was confirmed by derivatization to the corresponding known 2-C-methyl derivative 8 ) by radical reduction. Hydride reduction of 3 with NaBH4 in D·Glc.

The title compound was synthesized from D-glucose as a key intermediate of DInositol-I,4,5-triphosphate synthesis without doing any optical resolution by utilizing C 2 symmetry.Since the discovery of the role of D-myo-inositol 1,4,5-triphosphate( IP 3 ,1) as an intracellular second messenger for calcium mobilization,I) a great biological interest in IP) has been increased In order to explore the biochemical processes, a simple, general, and efficient methodology for chemical syntheses of IP 3 , 1 and its derivatives is required. Up to date, for the synthesis of IP 3 and its derivatives, myoinositol has been mainly used as a starting material. But previous methods have required a optical resolution. Here we now report a new strategy for synthesizing the partially-protected key intermediate,was prepared from Dglucose in 56 % yield (3 steps) (Scheme 1 ). 6-Deoxyhex-5-enopyranoside derivative(4) was synthesized by treatment of 3 with sodium iodide, tetrabutylammonium iodide, 1,8-diazabicycIo[5,4,O]undec-7-ene(DBU) and molecular sieves 4A in dimethyl sulfoxide(DMSO) at 80-110°C ( one pot reaction,3) 63% yield). Detosylation of compound 4 followed by protection with benzyl group gave methyI2-0-benzyl-6-deoxy-3,4-di-Omethoxymethyl-a-D-xylo-hex-5-enopyranoside (5) in 87% yield. Ferrier reaction 4) of 5 gave partiallyprotected 2,3,4,5-tetrahydroxycyclohexanone derivative(6) which was treated with acetic anhydride in pyridine to give the corresponding enone derivative (7) in 77% yield(2 steps). Reduction of 7 with sodium borohydridecelium chloride in ethanol, followed by benzylation of hydroxyl group gave protected cyclohexenol derivative[8: NMR (CDCI); f> 3.79 and 4.17 ppm ( each dd, 4H, A2B2, J=5.1, 2.4 Hz), 5.73 (s, 2H)] in 89% yield (2 steps). Oxidation of compound 8, which has C 2 symmetry axis, with osmium tetroxide gave partially protected myo-inositol derivative(9) in 83% yield. Regioselective protection of vicinal hydroxyl group by use oftris butyl stanyl oxide and methoxymethyl chloride, followed by benzylation of remaining hydroxyl group gave full OH

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.