José M. Vega-Pérez

Alkylating agents from sugars. Alkyl hexopyranoside derivatives as carrier systems for chlorambucil

Chlorambucil derivatives involving alkyl 2-aminodeoxy sugars have been synthesized in good yield by coupling the chlorambucil moiety to positions C-2 or C-3 of the sugar, directly or via a spacer. The starting material was easily available from 2-acetamido-2-deoxy-D-glucose. The final compounds were tested for cytotoxicity, and some of those that presented the best results were studied for inhibition of cell proliferation.

Isoprenyl-thiourea and urea derivatives as new farnesyl diphosphate analogues: synthesis and in vitro antimicrobial and cytotoxic activities.

A series of new isoprenyl-thiourea and urea derivatives were synthesized by the reaction of alkyl or aryl isothiocyanate or isocyanate and primary amines. The structures of the compounds were established by (1)H NMR, (13)C NMR, MS, HRMS and elemental analysis. The new compounds were screened for in vitro antimicrobial activity against seven strains representing different types of gram-positive and gram-negative bacteria. More than a third of the synthesized compounds showed variable inhibition activities against the tested strains. Best antimicrobial activities were found for those thiourea analogues with 3-methyl-2-butenyl, isobutyl or isopentyl groups and aromatic rings possessing electron withdrawing substituents. The new compounds were also subjected to a preliminary screening for antitumoral activity. The presence of a highly lipophilic group and an electron withdrawing group in the aromatic rings enhanced anticancer activity of the synthesized compounds, showing in most cases more activity than that of the controls.

Alkylating agents from sugars. Cyclophosphamides derived from 2-amino-2-deoxy-d-allose

Abstract Cyclophosphamides derived from alkyl 2-amino-4,6- O -benzylidene-2-deoxy- β - d -allopyranosides have been synthesized with good yield by treatment of the corresponding 2-amino-2-deoxy- d -allose derivatives with bis(2-chloroethyl)phosphoramide dichloride. The ring-forming reaction took place with very high diastereoselectivity. Subsequent hydrogenolysis gave excellent yields of cyclophosphamides derived from alkyl 2-amino-2-deoxy- β - d -allopyranosides, with hydrophilicity greater than that of the precursors. The starting material was easily available from 2-acetamido-2-deoxy- d -glucose.

Stereoselective synthesis of oxiranes using oxazolidines derived from 2-amino-2-deoxy-d-allose as chiral auxiliaries

Abstract The synthesis of 2,3-epoxyamide derivatives of 2-amino-2-deoxy- d -allose is described. Epoxidation of the corresponding α,β-unsaturated amides with m -CPBA took place with better stereoselectivity when an oxazolidine ring was fused to the 2,3-positions of the sugar molecule. In most cases, both stereoisomers could be isolated and characterized. The stereochemistry of the new stereogenic centers was then determined by cleavage of the oxirane moiety from the chiral auxiliary, which was also recovered.

Glycosyl Glycerol Derivatives as Drug Carrier System. Stereoselective Synthesis of EpoxyalkylN-Acyl-β-D-glucopyranosides and Their Reactivity with Nucleophiles

The synthesis of alkenyl 2-acylamino-4,6-O-benzylidene-2-deoxy-β-D-glucopyranosides from N-acetyl-D-glucosamine is described. The oxidation of alkenyl glycosides with m-CPBA gives the corresponding oxiranes in good yields, and with high stereoselectivity. Analogues of glycosyl glycerol derivatives, which can be used as drug carriers, were obtained by various ring-opening reactions with different nitrogen, sulfur, and carbon nucleophiles.

Stereoselective synthesis of epoxyalkyl glycoside precursors of glycosyl glycerol analogues from alkenyl glycosides of N-acetyl-d-glucosamine derivatives☆

Abstract The synthesis of epoxyalkyl glycoside derivatives of N-acetyl- d -glucosamine is described. Epoxidation of the corresponding alkenyl glycosides with m-CPBA took place with different stereoselectivity depending on the nature of the unsaturated system and the protecting groups on the sugar moiety. The configuration of the newly formed stereogenic centres has been confirmed unequivocally by chemical correlation.

Stereoselective synthesis of oxazolidines from 2-amino-2-deoxy-d-allose derivatives and their reactivity with nucleophiles

Abstract The use of 2-amino-2-deoxy- d -allose in the synthesis of oxazolidines is described. The reaction takes place with total stereoselectivity in the preparation of both simple oxazolidines (from aldehydes as reagent) and bicyclic oxazolidines (from chlorocarbonyl compounds and keto-acids as reagents). The reactivity of the obtained oxazolidines with hydride and alkylmagnesium chlorides is also described.

Oxazolidines from sugars. III: A new method for N-alkyl and N,N-dialkyl-D-glucosamine derivatives

Abstract Title compounds can be synthesised by an easy two-step method from the readily available benzyl 2-acylamino-4,6-O-benzylidene-2-deoxy-D-glucopyranosides (1–5), by nucleophilic cleavage of the oxazolidine ring previously formed between the positions 2 and 3 of the aminosugars.

Oxazolidines from sugars: conformationally restricted derivatives of muramic acid

Abstract The syntheses are described of four conformationally restricted derivatives of muramic acid based on the α- d -glucopyrano[2,3- d ]oxazolidine ring system.

A novel general method for 2-aminoglycal synthesis

Abstract The first general method for N,N -substituted 2-aminoglycals is reported. We describe the syntheses of 2-[( N -acyl- N -alkyl)amino] and 2-[( N,N -dialkyl)amino]-1,5-anhydro-4,6- O -benzylidene-2-deoxy- erythro -hex-1-en-3-uloses by oxidation of glycoside derivatives of N,N -substituted-2-aminosugars using two oxidant systems. Reactions proceed with good yields.