Ettore Mastrorilli

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.

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.

Efficient Differentiation of the Hydroxyl Groups of 3,4-O-Isopropylidene-D-Galactopyranosides by Lipase Catalyzed Esterification and De - Esterification

Abstract The Pseudomonas sp. (LPS) promoted acyl transfer from vinyl acetate to selected 3,4-O-isopropylidene-D-galactopyranosides takes place in a completely selective manner giving in high yield the corresponding 6-O-acetates. The acetylation rate is strongly dependent on the type and the orientation of the aglycon, varying from a maximum of reactivity for the 1-deoxy derivative, 1,5-anhydro-3,4-O-isopropylidene-D-galactitol (1d), to a minimum for β configurated alkyl glycosides and showing a complete loss of reactivity for 3′,4′:2,3:5,6-tri-O-isopropylidenelactose dimethyl acetal (1e). The latter compound is, however, selectively 6′-O-esterified in good yield by lipase from Candida Antarctica and vinyl acetate. Also the course of the enzymatic hydrolysis of 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosides 2 is dependent on the type of the aglycon, both for the reaction rate and the selectivity. The 2-O-acetates 4 are selectively obtained in good yields with porcine pancreatic lipase (PPL) prom...

Convenient diastereospecific synthesis of a rociverine precursor and its resolution by lipase-catalyzed transesterification

Abstract (±)-1-Cyclohexyl- c -2-hydroxymethyl- r -1-cyclohexanol 3 , a precursor of the antimuscarinic drug Rociverine 1 , was obtained diastereospecifically in very high yield, from the Grignard reaction between C 6 H 11 MgCl and an appropriately protected 2-(hydroxymethyl)cyclohexanone. The preparation of enantiomerically enriched cis diol (+)-(1R,2S)- 3 and the corresponding 2-acetoxymethyl derivative (+)-(1S,2R)- 12 was achieved by lipase PPL-catalyzed transesterification of racemic diol (±)- 3 .

Preparation and evaluation of the in vitro erythroid differentiation induction properties of some esters of methyl 3,4-O-isopropylidene-β-d-galactopyranoside and 2,3-O-isopropylidene-d-mannofuranose

Two series of glycide esters of short fatty acids, designed for avoiding intramolecular transesterification, were prepared and tested for in vitro erythroid differentiation induction activities using the K562 cell line as experimental system. The 6-O-isobutiryl and pivaloyl derivatives of methyl 3,4-O-isopropylidene-beta-D-galactopyranosides as well the same 1-O-esters of 2,3-O-isopropylidene-alpha- and beta-D-mannofuranose exhibit biological activities much higher that the corresponding acids and could be proposed as possible agents to modulate production of embryo-fetal hemoglobins by human erythroid cells.

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.

The influence of a t-Butyl group on the conformational equilibrium and the Hydrogen Bromide catalyzed isomerization of 2-Bromocyclohexanones

Abstract The trans and cis diastereoisomers of 2-bromo-6-t-butylcyclohexanone (7 and 8) and of 2-bromo-3-t-butylcyclohexanone (10 and 9) have been prepared and subjected to hydrogen bromide catalyzed isomerization. Whereas bromoketones 7 and 8 underwent only epimerization, isomers 9 and 10 were completely converted into an equilibrium mixture of cis- and trans-2-bromo-5-t-butylcyclohexanone (12 and 13). The spectral parameters (IR, UV, NMR), as well as the equilibrium distribution of the couple 7-8, were consistent with chair conformations for compounds 7, 8 and 9, but indicated for isomer 10 a flexible form in which both the bromine-t-butyl steric interaction and the electrostatic repulsion between Br and CO group are relieved.

Acid-catalyzed and enzymatic hydrolysis of trans- and cis-2-methyl-3,4-epoxytetrahydropyran

Whereas the acid-catalyzed hydrolysis of trans- and cis-3,4-epoxy-2-methyltetrahydropyran gives the corresponding diols by opening both at C-4 and C-3 (64% attack at C-4 in the trans-epoxide, 86% in the cis-epoxide), the hydrolysis of the same substrates catalyzed by rabbit liver microsomal epoxide hydrolase is entirely regiospecific and involves in both cases exclusive attack at C-4. The racemic cis-epoxide reacts at a faster rate than the trans. The 2R,3R,4S-enantiomer of the latter epoxide reacts at a much faster rate than its antipode to yield the (–)-(2R,3R,4R)-diol which is isolated at least 98% optically pure up to almost 50% conversion when starting from the racemic substrate. A reference sample of optically pure (+)-(2S,3S,4S)-diol was prepared from L-rhamnose. The enantiomeric excess of the (–)-(2R,3R,4R)-diol was also determined more precisely through g.l.c. analysis of diastereoisomeric MTPA esters. The present results confirm previous hypotheses on the topology of the hydrolase active site and emphasize the overriding importance of the orientation of a lipophilic substituent near the oxirane ring.