José I. Candela

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.

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.

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.

New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure–activity Relationships

The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and structure-activity relationships of a small molecules library. We have identified six phenylpiperazine derivatives that significantly inhibited HAdV infection. These six compounds showed the capacity to block HAdV and, in addition, human cytomegalovirus (HCMV) replications at low micromolar concentration, with little or no cytotoxicity. On the basis of our biological studies, these molecules block HAdV and HCMV infections in different phases of their life cycle, providing potential candidates for the development of a new family of antiviral drugs for the treatment of infections by DNA viruses.

Electron impact and chemical ionization mass spectra of N -alkyl and N,N -dialkylaminosugar derivatives

The electron impact mass spectra of 46 new alkyl 4,6-O-benzylidene-2-amino-N-alkyl and N,N-dialkyl-2-deoxy-D-hexopyranosides were examined. Three general pathways of fragmentation were encountered, the importance of which depends above all on the nature of aglycon and also on the nature of nitrogen substituents.

The C 3 H 6 O +• fragment from 1,4-dioxane +• revisited

The electron impact spectra of 2-N-alkyl, 2-N-acyl-2-N-alkyl and 2-N,N-dialkyl aminosugar derivatives, as well as 2-aminosugar derivatives themselves, all show an [H1 2 + 13] ion. In previous work, it was considered that this ion was derived from the [M – OR] ion and was designated as [M – OR – 178]. In the present work, the structure and origin of the [H1 2 + 13] ion is studied in detail, and it is demonstrated that it originates first from the molecular ion, via a primary fragmentation, and second from the [M – OR] ion, in both cases by a [3 + 3] cleavage of the pyranose ring.

Mass Spectra of N-Alkyl and N,N- Dialkylaminosugar Derivatives. Chemical Evidence for the Different Pathways of Fragmentation

The electron impact ionization mass spectra of new alkyl (and phenyl) 4,6-benzylidene-2-amino-N-alkyl- and N,N-dialkyl-2-deoxy-D-hexopyranosides and benzyl (and phenyl) 4,6-O-benzylidene-2,3-di-O-alkyl-D- hexopyranosides were examined. Three general pathways of fragmentation were encountered. The competition the two most important pathways of fragmentation ([M - R 1 O→]# and H routes) depends primarily on the nature of the aglycone and secondarily on the nature of nitrogen substituents. In addition, relationships between the different peak intensities in each pathways of fragmentation depend exclusively on the nature of nitrogen substituents. Definitive chemical evidence for different pathways of fragmentation was found.