G. Berti

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.

4,6-O-BENZYLIDENE-D-GLUCOPYRANOSE AND ITS SODIUM-SALT - NEW DATA ON THEIR PREPARATION AND PROPERTIES

An improved method for the preparation of 4,6-O-benzylidene-D-glucopyranose (BG), and new or correlated data on its 1H and 13C NMR spectra, specific rotations, and tautomeric equilibria, and on those of its anomeric sodium salt (BGNa), are reported. Evidence is presented in favour of the hypothesis that crystalline BGNa exists entirely in its beta-anomeric form and that it can be useful in the access to beta-glucosides in reactions with strong electrophiles under strictly heterogeneous conditions.

New methods for the preparation of 1-phenyl-trans-cyclohexane-1,2-diol

Abstract In contrast with previous reports, it was found that the reaction of 1-phenylcyclohexene with peroxyformic acid is not entirely stereospecific, but gives some trans -1-phenylcyclohexane-1, 2-diol (IV) beside the cis -isomer (III). The reaction of 1-phenylcyclohexene oxide (II) with formic acid yielded a similar mixture of III and IV, while addition of trichloroacetic acid in benzene was entirely cis -stereospecific. Reaction of the epoxide II with potassium hydroxide took place only under very drastic conditions to give a small yield of III, while sodium 2-dimethylaminoethoxide added exclusively in a trans way, leading to the amino ether X, which was easily transformed into the trans -glycol IV. The latter compound was also the main product of the borohydride reduction of 2-hydroxy-2-phenylcyclohexanone (IX). Possible explanations of the observed stereochemical results are discussed.

Double reductive amination of l-arabino-hexos-5-uloses: A diastereoselective approach to 1-deoxy-d-galactostatin derivatives☆

Abstract The double reductive amination of l - arabino -hexos-5-ulose with benzhydrylamine and NaBH 3 CN takes place in a diastereospecific manner giving in moderate chemical yield (36 %) the galactosidase inhibitor 1-deoxy- d -galactostatin. The aminocyclization of 2,6- di -O- benzyl- l -arabino- hexos-5-ulose is more complicated giving results dependent from the type of amine: with ammonia or methylamine a mixture of C-5 epimeric 1-deoxyazapyranoses ( d -galacto l -altro ratio ≈ 4:1 ) is obtained in 45–65% combined yield, while with benzhydrylamine substantial amounts of an acyclic 1-deoxy-1-benzydrylamino-hexitol (10 % yield) is isolated together with the expected 1-deoxy-azasugars of the d - galacto and l - altro series.

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.

Regio- and stereochemistry of the acid catalyzed and of a highly enantioselective enzymatic hydrolysis of some epoxytetrahydrofurans.

3,4-Epoxytetrahydrofuran is hydrolyzed by rabbit liver microsomal epoxide hydrolase (MEH) with a high preference for the attack by water at the (S) epoxide carbon to give the (R,R)-diol with an e.e. of 96.5±0.3%. In the acid catalyzed hydrolysis of trans-3,3a-epoxyoctahydrobenzofuran the oxirane ring is opened with inversion exclusively on the tertiary carbon atom to give the corresponding trans-diol, whereas hydrolysis of the cis isomer is less regioselective, the ratio of attack at the tertiary and secondary carbons being 81:19. The MEH catalyzed hydrolysis of the same two substrates occurs exclusively at their secondary epoxide carbons and with a very high enantioselectivity: only enantiomers of configuration (3S,3aR) of the cis- and trans-epoxide are substrates for the enzyme and give the corresponding (3R,3aR)-diols with at least 98% e.e., the corresponding (3R,3aS)-epoxides being totally resistant to enzymatic hydrolysis. These results agree well with previously formulated rules on steric requirements of MEH subtrates. Absolute configurations and optical purities of new chiral compounds were obtained by chiroptical, NMR and chiral chromatographic techniques. Conformations of the octahydrobenzofuran derivatives were derived from coupling constants and found to be in fairly good agreement with those deduced from molecular mechanics calculations.

The epoxide hydrolase catalyzed hydrolysis of trans-3-bromo-1,2-epoxycyclohexane. A direct proof for a general base catalyzed mechanism of the enzymatic hydration.

Abstract The hydrolysis of (±)- trans -3-bromo-1,2-epoxycyclohexane in the presence of rabbit liver microsomes was investigated, and found to yield, beside c -3-bromocyclohexane- r -1, t -2-diol, 2,3-epoxycyclohexanol. It was demonstrated that the latter compound was the only product of the enzymatic reaction, whereas the diol resulted from a non enzymatic hydration in the reaction medium. These data provide the first direct proof for a general base catalysis in the enzymatic epoxide hydration, previously hypothesized on the basis of several lines of indirect evidence, and disprove alternative mechanisms involving protonation of the oxirane oxygen.

The asymmetric bromination of alkenes in the presence of Cinchona alkaloids

Abstract The bromination of several acyclic and cyclic alkenes in the presence of Cinchona alkaloids produces optically active dibromides. The influence of the configuration of the alkaloid and of the structure of the alkene on the stereochemical results of the reaction has been investigated. The possible mechanism of the asymmetric bromination, and its use as a method for determining the absolute configuration of vicinal dibromides are discussed.

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 d-amicetose and l-rhodinose from l-glutamic acid

Abstract l -Glutamic acid has been converted into a separable mixture of d -amicetono- and l -rhodinono-γ-lactones by a sequence involving transformation into (S)-γ-carboxy-γ-butyrolactone (2), conversion of 2, conversion of 2 into the corresponding methyl ketone by the diazoketone route, and selective reduction with zinc borohydride or borane-methyl sulfide. Reduction of the two lactones with di-isobutylaluminium hydride gave the corresponding deoxy sugars. In spite of some improvements in the preparation of 2, the optical yield of this step was only ∼80%, but one crystallisation from chloroform raised the optical purity to 96%. The subsequent steps produced a loss in optical purity of only 4%.