The synthesis and resolution of (±)-1,5,6-tri-O-benzyl-myo-inositol

Synthesis of d- and l-myo-Inositol 1,4,6-Trisphosphate, Regioisomers of a Ubiquitous Second Messenger

“…The trans-5,6-diol of 6 was now exposed, and it was envisaged that the 6-position would be more reactive toward tin-mediated alkylation over the 5-position. 22 Thus, treatment of diol 6 with a mixture of dibutyltin oxide, tetrabutylammonium iodide, and p-methoxybenzyl chloride gave three products, with the required 9 as the major product. The 1 H NMR spectrum distinctly showed the 5-OH coupling to C-5-H, δ ) 3.43 (ddd), where upon D 2 O exchange the ddd collapsed to a dd.…”

“…The trans -5,6-diol of 6 was now exposed, and it was envisaged that the 6-position would be more reactive toward tin-mediated alkylation over the 5-position …”

“…Thus, L-1,2,4,5-tetra-O-benzyl-myo-inositol (22) was synthesized from D-1,4-di-O-allyl-2,3,5-tri-O-benzyl-6-O-(p-methoxybenzyl)-myo-inositol (11a). The p-methoxybenzyl group was removed from 11a by acidic hydrolysis to provide D-1,4-di-O-allyl-2,3,5-tri-O-benzyl-myo-inositol (20) as a syrup.…”

“…Gigg et al 30 prepared racemic 21 as a syrup; however, in our hands, chiral 21 was a low melting point solid. The allyl groups were then removed in a onepot reaction using palladium on carbon in the presence of toluene-p-sulfonic acid to give D-2,3,5,6-tetra-O-benzylmyo-inositol (22) (the same as L-1,2,4,5-tetra-O-benzylmyo-inositol). The specific rotation was found to be [R] D ) +4.0°and agreed well with the literature value, 30 as did the melting point.…”

Synthesis of Differentially Protectedmyo- andchiro-Inositols fromd-Xylose: Stereoselectivity in Intramolecular SmI2-Promoted Pinacol Reactions

“…SmI 2 -promoted pinacol coupling of 6a under standard conditions 36 [SmI 2 (3 equiv), t-BuOH (3 equiv), THF, -78 to 20°C over 5 h] produced a disappointing 1:2.5 ratio of 7a:8a (R = TIPS). The structures of 7a and 8a were established as previously described 33 and confirmed by desilylation (Bu 4 NF, THF), to produce known tribenzyl-myo-inositols 7i 37,38 and 8i. 39 Since 7a has the correct differential protection pattern for application in the synthesis of most of the known natural myo-inositol glycan (IG) structures, 26,[40][41][42][43][44][45][46][47][48][49][50][51] we sought to alter the stereoselectivity in the pinacol reaction to favor 7.…”