Sanjib Bera

A new general synthesis of isomeric nucleosides

Abstract An efficient new method for the synthesis of isonucleosides is described. The key step in the synthesis was the direct coupling of purine and pyrimidine bases with the cyclic sulfate of a carbohydrate intermediate. This reaction proceeded with high regiospecificity and stereospecificity.

Nucleosides with furanyl scaffolds

Synthesis of purine and pyrimidine nucleosides with furanyl scaffolds is described. The 2-functionalized tetrahydrofuranol derivatives 12 and 15 were coupled with nucleobases through the Mitsunobu reaction. The methodology developed is general and can also be applied for an efficient synthesis of apionucleosides. In addition, the methodology was used for the synthesis of the unsaturated purine nucleoside 22. However, when the elimination reaction used to produce 22 was applied to the pyrimidine case, the stable anhydro compound 24 was produced. The structures of 18 and 22 were confirmed by single-crystal X-ray data. Antiviral evaluation was performed.

3′-Deoxy-3′-(vinylsulphonyl)thymidine — a new reactive analogue of AZT: its synthesis and reactivities towards various nucleophiles#

Abstract A reactive triatomic analogue of AZT, 3′-deoxy-3′-(vinylsulphonyl)thymidine has been synthesised from easily accessible starting material. The vinyl-sulphone nucleoside was reacted with a variety of nucleophiles to generate new classes of modified nucleosides where the functional groups were attached to the C-3′ of a nucleoside through flexible ethyl sulphone spacer.

Isonucleosides with Exocyclic Methylene Groups

Synthesis of isonucleosides 13, 14, 16, and 17, bearing an exocyclic methylidene group at the sugar moiety, starting from a 3-keto sugar is described. The keto compound was converted to the methylene-sugar 10b (Scheme 1), which was coupled with nucleobases by means of the Mitsunobu reaction. The coupling reaction with adenine and 8-azaadenine produced both the N9- and N3-nucleosides (see 13 and 14, resp.; Scheme 2). The structures of 13a and 14a were confirmed by single-crystal X-ray data. Synthesis of the pyrimidine compounds was also approached from the β-amino sugar 20 that was prepared using a Gabriel-synthesis methodology (Scheme 3).

Cyclopropyl and Related Analogs of the Anti-HIV Compound, Isodideoxyadenosine

Abstract Novel 3′-substituted isonucleoside analogs were designed on the basis of the similarities of their electrostatic potential with the active anti-HIV compound, (S,S)-isodideoxy-adenosine. The key synthetic step involved coupling between the dideoxygenated sugar derivatives, 10 and 14, and adenine under Mitsunobu conditions. Anti-HIV data are mentioned.

Synthesis and Antiviral Studies of Unsaturated Analogues of Isomeric Dideoxynucleosides

Novel isomeric dideoxynucleosides with unsaturation in the carbohydrate moiety have been synthesized. For example, isod4A was synthesized through a rearrangement reaction involving a cyclonucleoside. Support for the structures of both purine and pyrimidine d4 compounds came from UV, NMR, HRMS and single crystal X-ray data. Interestingly, the single crystal X-ray data for isod4C shows that the base is almost orthogonal to the carbon-carbon double bond of the sugar moiety. Consistent with this is the observation that the UV data of this compound does not show a bathochromic shift compared to the saturated compound implying that the pi-bond is not in conjugation with the pyrimidine base.

One-step synthesis of C-2 dialkylamino-substituted 2',3'-O-anhydro-lyxo-uridines : first report on the opening of 2,2'-O-anhydro-bridge of 2,2'-O-anhydrouridine by secondary amines

Abstract Secondary amines successfully opened the 2,2′-O-anhydro-bridge of 2,2′-O-anhydrouridines 8a and 8b in presence of 3′-O-mesyl group to produce compounds 10a-13a and 10b-13b, a new class of isocytidine derivatives.

Thermal degradation of sugar-modified uridine N-oxides: Olefination, oxazolidination and rearrangements

Abstract The degradation pattern of the N-oxides of various tertiary aminouridines is established. The N-oxide of 3′-deoxy-3′-morpholino-arauridine generated double bonds in the carbohydrate moiety without much selectivity, whereas epimino uridine N-oxides generated only d4U. Oxazolidine derivatives were formed from the N-oxides of 3′-deoxy-3′-N-pyrrolidino/morpholino-2,2′-O-anhydrouridines and 3′-deoxy-3′-N-pyrrolidino/morpholino-2′-O-mesylarauridines. 2′-Deoxy-2′-N-pyrrolidino/morpholino-2′-O-mesylxylouridines produced rearranged products 3′-O-N-pyrrolidino/morpholino-2,2′-O-anhydrouridines.

Acyclic Nucleosides Bearing a Furanyl Scaffold

Synthesis of acyclic nucleosides bearing a furanyl scaffold is described. The approach involved the construction of the base moiety onto a dihydrofuranyl intermediate. While the A and C analogues did exhibit some substrate activity toward deoxycytidine kinase, the compounds were devoid of any significant anti-HIV activity. The project described was supported by Grant Number AI 32851 from the National Institutes of Health. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

SYNTHESIS OF NOVEL ISOMERIC DIDEOXYDIDEHYDRONUCLEOSIDES

Methodologies for the synthesis of novel isomeric dideoxynucleosides with unsaturation in the carbohydrate moiety have been developed. An example of the synthesis (Isod4A) is presented. Antiviral studies are in progress.