Fabrizia Colonna

New results in the isopropylidenation of galactopyranosides. Useful intermediates for the synthesis of galactose derivatives.

Abstract Reaction of several α- and β-galactopyranosides with 2,2-dimethoxypropane produced up to five types of mono-, bis-, and tris(isopropylidene)acetals, among which the 3,4-0-iso-propylidene-6-0-(2-methoxyisopropyl) derivatives can be obtained in high yield and be useful intermediates for selective syntheses of 2-, 6-, and 2,6-0-substituted galactose derivatives.

A highly diastereoselective synthesis of dl-oleandrose

Abstract Racemic oleandrose (2,6-dideoxy-3-O-methyl-arabino-hexone) has been obtained starting from the Diels-Alder adduct between 4-methoxy-3-buten-2-one and isobutyl vinyl ether, which was converted into a mixture of the isobutyl β- and α-oleandrosides through hydroboration-oxidation. The latter reaction is highly diastereoselective since attack by borane takes place exclusively anti to the OMe group: none of the diasteroisomeric cymarosides are formed. The only side-products are small amounts of the isobutyl β- and α-amicetodies formed by a demthoxylation occuring during the hydroboration step.

A facile conversion of 3,4-O-isopropylidene-β-d-galactopyranosides into 4-deoxy-α-l-threo-hex-4-enopyranoside and l-arabino-hexos-5-ulose derivatives

Treatment of O-protected 3,4-O-isopropylidene-β-d-galactopyranosides with tert-BuOK in N,N-dimethylformamide or methyl sulfoxide produces 4-deoxy-α-l-threo-hex-4-enopyranosides in good yields. The corresponding α-anomers and the non-O-protected derivatives are resistant to this treatment. Reaction of methyl 4-deoxy-2,6-di-O-methyl-α-l-threo-hex-4-enopyranoside with 3-chloroperbenzoic acid in CH2Cl2 gave a crystalline adduct that was hydrolyzed to 2,6-di-O-methyl-l-arabino-hexos-5-ulose.

Synthesis of 2,3:4,6-di-O-isopropylidene derivatives of alkyl α- and β-d-galactopyranosides, and elucidation of structure by n.m.r. and x-ray analysis

Abstract Kinetically controlled reaction of 4.5 equiv. of 2-methoxypropene with some alkyl α- and β- d -galactopyranosides gave the 2,3:4,6-di- O -isopropylidene derivatives in high yields (80–85%). With 2 equiv. of 2-methoxypropene, benzyl β- d -galactopyranoside gave the 4,6- and the 3,4-monoacetals in the ratio 30:1 together with ∼20% of the 2,3:4,6-diacetal. The structures of methyl 2,3:4,6-di- O -isopropylidene-α- and -β- d -galactopyranosides were determined by X-ray analysis. The former crystallised in the orthorhombic system, P 2 1 2 1 2 1 , with a = 5.503, b = 16.105, c = 16.822 A, and Z = 4, the latter in the monoclinic system, P 2 1 , with a = 10.400, b = 13.344, c = 11.647 A, β = 111.50, and Z = 4. The α anomer and the two molecules of the β anomer had the d -galactopyranoside and the 1,3-dioxane rings in twist-chair conformations and the dioxolane ring in a half-chair conformation. N.m.r. spectroscopy suggested the occurrence of similar conformations in solution.

Preparation of isobutyl 3,4-anhydro-2,6-dideoxy-DL-α-lyxo-hexopyranoside and its kinetic resolution with microsomal epoxide hydrolase

Abstract Racemic isobutyl 3,4-anhydro-2,6-dideoxy-α- lyxo -hexopyranoside, 3, was prepared starting from the cycloadduct between 3-buten-2-one and isobutyl vinyl ether, through a sequence involving hydroboration-oxidation, mesylation, anomeric equilibration, elimination and epoxidation. The intermediate isobutyl 2,3,4,6-tetradeoxy-α-3-DL-hexenopyranoside, 10 was not stable under the conditions used for its preparation ( t -BuOK in DMSO), being converted in part into the corresponding 2-hexenopyranoside. Under the same conditions the -anomer of 10 was stable. Complete hydrolysis of DL-3 with aqueous NaOH, or with microsomial epoxide hydrolase (MEH) gave exclusively the xylo -diol (isobutyl DL-α-boivinopyranoside 5). When the hydrolysis with MEH was stopped near 50% conversion and the product diol was separated from the unchanged epoxide, both were optically active, the former having the L and the latter the D configuration. An ee of at least 96% was found for both the diol and the epoxide by the use of a chiral shift reagent.