Pier Luigi Barili

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.

SUBSTITUTED 1,2,3-TRIAZOLO[1,5-A]QUINAZOLINES: SYNTHESIS AND BINDING TO BENZODIAZEPINE AND ADENOSINE RECEPTORS

This paper reports the synthesis and evaluation of the biological affinity towards benzodiazepine and A(1) and A(2A) adenosine receptors of some 3-ethoxycarbonyl or 3-phenyl-substituted 1,2, 3-triazolo[1,5-a]quinazolines. Starting from the appropriate chloro-substituted phenylazides, the series of 7 or 8 chloro-substituted triazoloquinazolines were prepared. Nitration reactions of the triazoloquinazoline ring and chlorination reactions of the hydroxyl group in the 5 position of the same ring are also reported. By nucleophilic displacement of halogen, the corresponding 5-amino derivatives and some analogous derivatives bearing cyclohexylamino and p-toluidino substituents were obtained. The binding assays showed a generalized decrease in the affinity towards the benzodiazepine receptors and confirmed a moderate affinity towards the A(1) adenosine receptors in comparison with the previously studied triazoloquinazoline 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.

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 Facile "One‐Pot" Synthesis of 2,9‐Disubstituted 8‐Azapurin‐6‐ones (3,5‐Disubstituted 7‐Hydroxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidines).

A series of title compounds have been synthesized by utilising benzylazide, cyanoacetamide, ethyl or methyl esters of aliphatic or aromatic carboxylic acids and sodium ethoxide as catalyst.

A new highly diastereoselective synthesis of epi-inositol from d-galactose

Abstract The inosose derivative 3 was obtained with high stereoselectivity by intramolecular aldol condensation of the aldohexos-5-ulose derivative 2 , and it was selectively reduced and debenzylated to give epi -inositol in high yield. The stereochemistry and the preferred conformations of compounds 3 – 7 were determined through 1D and 2D NMR experiments.

Improved preparation of 2,3:5,6:3′,4′-tri-O-isopropylidenelactose dimethyl acetal and its 6′-O-(1-methoxy-1-methylethyl) derivative

Abstract Efficient preparations both of 2,3:5,6:3′,4′-tri- O -isopropylidenelactose dimethyl acetal ( 5 , 95% yield) and its 6′- O -(1-methoxy-1-methylethyl) derivative (65% yield), useful intermediates for the conversion of lactose into biologically relevant oligosaccharides, by ‘one-pot’ acetonation procedures with 2,2-dimethoxypropane are reported. The acetonation of 5 with 2-methoxypropene in the presence of pyridinium tosylate and 4 A molecular sieves unexpectedly revealed the formation, in a first kinetic reaction phase, of similar amounts of the 2′- O - and 6′- O -(1-methoxy-1-methylethyl) acetals. The structures of all new products were fully characterized by NMR analyses, which also allowed some deductions on the conformation of the galactopyranosyl rings.

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.

1,2,3-Triazolo [1,5-a] [1,4]- and 1,2,3-triazolo [1,5-a]-[1,5]benzodiazepine derivatives : synthesis and benzodiazepine receptor binding

This paper reports the synthesis of new 1,2,3-triazolo[1,4]benzodiazepine and 1,2,3-triazolo[1,5]benzodiazepine derivatives and their evaluation toward benzodiazepine receptors. Receptor affinity gradually and remarkably increases by moving the nitrogen atom of the central ring from position 3 through 4 to position 5, to give the most effective compound 6a (Ki = 150 nM). N-methylation of the diazepine ring (7a) lowers receptorial binding. Introduction of a chlorine atom on the benzene ring doubles the Ki value (6b) which remains unaltered by the N-methylation (7b).

Reinvestigation of reductive butylation of aminophthalimides: new compounds with local anesthetic activity

A careful reinvestigation on reductive butylation of N-β-diethylaminoethyl aminophthalimides showed that this reaction yields the corresponding butylaminophthalimides together with the 1-hydroxy butylaminophthalimidines. The same reaction carried out on N-β-diethylaminoethyl aminophthalimides hydrochlorides gave the corresponding butylamino phthalimidines. The 1-hydroxy butylaminophthalimidines 5 and 6, tested for their local anesthetic properties, exhibited interesting activity comparable to that of Novesine, showing hence a potential therapeutic efficacy.