Fiamma Ronchetti

Enzymic acylation of sugars. Rationale of the regioselective butyrylation of secondary hydroxy groups of D- and L-galacto and mannopyranosides

Abstract Methyl 6-O-butyryl-α-D- and -L-galactopyranoside and methyl 6-O-butyryl-α-D- and -L-mannopyranoside, which present three contiguous secondary hydroxy groups in different orientations, have been acylated using three hydrolytic enzymes. Porcine pancreatic, Candida cylindracea, and Pseudomonas fluorescens lipases in organic solvents. Some generalization of the obtained results is discussed. Methyl 6-O-butyryl-α-D- and -L-galactopyranoside and methyl 6-O-butyryl-α-D- and -L-mannopyranoside, which present three contiguous secondary hydroxy groups in different orientations, have been acylated using three hydrolytic enzymes. Porcine pancreatic, Candida cylindracea, and Pseudomonas fluorescens lipases in organic solvents. Some generalization of the obtained results is discussed.

Synthesis of C-glycosyl compounds by the wittig iodocyclization procedure. Differences from mercuriocyclization

Abstract Various sugars were C -glycosylated by treatment with methylenetriphenyl-phosphorane and subsequent iodocyclization of the resulting hept- and hex-enitols. In all cases, a C glycofuranosyl compound was obtained, except for 3,4,5,7-tetra- O -benzyl-1,2-dideoxy- d - manno -hept-1-enitol which yielded a C -pyranosyl compound. High stereoselectoin, with formation of the 1,2- cis adduct as major product, was observed when an asymmetric center was present in the position adjacent to the double bond.

1,2-Dideoxy-3,4:5,7-bis-O-(1-methylethylidene)-D-gluco- and D-galacto-hept-1-ynitols: synthesis and conformational studies

Abstract 1,2-Dideoxy-3,4:5,7-bis- O -(1-methylethylidene)-D- gluco - and D- galacto -hept-l-ynitols were synthesized starting respectively from benzyl α,β-D-glucopyranoside and from benzyl α,β-D-galactopyranoside by bis-acetonidation, hydrogenolysis, Wittig reaction with chloromethylenetriphenylphosphorane, and dehydrohalogenation. The structures of the obtained compounds were confirmed by the NMR spectrocopic data which also allowed to determine the conformations of the molecules.

C-glycosides through the Wittig-cyclization procedure: observations on the influence of the nature of the substrate

Abstract The Moffatt C-glycosidation procedure was examined on different pyranoses; in glycopyranoses competitive elimination was observed in the Wittig reaction; all the other glycopyranoses investigated gave the Wittig product without elimination.

CD1a-binding glycosphingolipids stimulating human autoreactive T-cells: synthesis of a family of sulfatides differing in the acyl chain moiety

Abstract Native sulfatide (a mixture of 3-sulfated β- d -galactopyranosylceramides with different fatty acids at the ceramide moiety) is an antigen presented by CD1a proteins. Herein the preparation of four sulfatides, which are constituents of the natural mixture and bear palmitic, stearic, behenic or nervonic fatty acid chains, is described. Azidosphingosine was stereoselectively synthesized through a CuCN-catalyzed allylic alkylation of a hexenitol dimesylate derived from d -xylose; β-glycosylation of azidosphingosine with a suitable d -galactosyl trichloroacetimidate led, after reduction of the azido group, to the galactosylsphingosine skeleton, which was derivatized with the different fatty acids. Final regioselective 3-sulfation gave the desired sulfatides, which were tested for activation of sulfatide-specific and CD1a-restricted T-cell clones.

Inhibitory effects of fatty acid monoesters of 2-O-β-d-glucosylglycerol on Epstein–Barr virus activation

In a screening for cancer chemopreventing agents several glycosylglycerols were found to be active. In order to optimize the anti-tumor activity of this class of compounds, a series of 1-O-acyl-2-O-beta-D-glucopyranosyl-sn-glycerols differing in the acyl chain length, which varied from C4 to C18, were examined for their in vitro anti-tumor promoting effects on Epstein-Barr virus early antigen (EBV-BA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the compounds tested, the monohexanoyl derivative was the most active and, noteworthy, the most potent compound of the glycosylglycerol series hitherto known.

1-O-, 2-O- and 3-O-β-glycosyl-sn-glycerols: Structure - anti-tumor-promoting activity relationship

Abstract The inhibitory activity of synthetic glycosylglycerols on Epstein-Barr virus early antigen (EBV-EA) activation was evaluated. Among the series of 1- O -, 2- O - and 3- O - glycosylglycerols tested, 1- O - β -D-galactopyranosyl- sn -glycerol showed the highest inhibitory effect toward promotion.

Anti-tumor-promoting effects of glycoglycerolipid analogues on two-stage mouse skin carcinogenesis.

Four glycoglycerolipid analogues, 1-O-hexanoyl-2-O-beta-D-glucopyranosyl-sn-glycerol (1), 1-O-hexanoyl-2-O-beta-D-galactopyranosyl-sn-glycerol (2), 2-O-(6-O-hexanoyl-beta-D-galactopyranosyl)-sn-glycerol (3) and 2-O-(6-O-hexanoyl-alpha-D-galactopyranosyl)-sn-glycerol (4), potent in vitro inhibitors of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation, were submitted to an in vivo two-stage mouse skin carcinogenesis test, using dimethylbenz[a]anthracene (DMBA) and TPA. The study was extended to two deacylated galactosylglycerol structures, 1-O-beta-D-galactopyranosyl-sn-glycerol (5) and 3-O-beta-D-galactopyranosyl-sn-glycerol (6). All the tested compounds exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion, the 1-hexanoate 2 being the most active among the glycoglycerolipids until now studied.

A formal synthesis of 3-O-(4-methoxybenzyl)-azidosphingosine by a modified Julia olefination

Abstract The stereoselective construction of the d - erythro -azidosphingosine characteristic trans double bond was accomplished by condensation between tetradecanal and a heterocyclic sulfone derived from diethyl- d -tartrate, following the Kocienski modification of the Julia olefination.

Inhibitory effects of monoacylated 2-O-β-galactosylglycerols on Epstein-Barr virus activation : the significant role of the hexanoyl chain

Three series of monoacyl-2-O-beta-D-galactosylglycerols bearing an acyl chain of varying length, from C4 to C10, were studied due to their antitumor promoting effects on the activation of the Epstein-Barr virus early antigen (EBV-EA), such activation being induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study indicates that it is more the length of the acyl chain that is important for the activity, six carbon atoms resulting in maximum effect, rather than the position of the ester function and the nature of the sugar (galactose or glucose).