Todd B. Sells

Novel isomeric dideoxynucleosides as potential antiviral agents

Abstract Novel isomeric dideoxynucleosides with S,S absolute stereochemistry and involving the transposition of the base moiety from the normal 1′- to the 2′-position have been regiospecifically and stereospecifically synthesized. The synthetic approaches involved either direct coupling with inversion at the 2-position of a preformed dideoxygenated sugar using the base moiety as nucleophile (for purine isodideoxynucleosides) or construction of the base moiety onto a stereochemically defined amino sugar precursor (pyrimidine isodideoxynucleosides). These compounds possess extremely high stability with respect to “glycosidic” bond cleavage and enzymatic deamination. Antiviral data suggest that the most active compound was levorotatory S,S-isodideoxyadenosine.

Synthetic approaches to novel cis and trans dideoxynucleosides of the apiose family

Abstract Stereoselective synthesis of the complete family of optically active dideoxygenated nucleosides of the apiose family have been developed. The chiral aldodiol system 7 , a key intermediate in this synthesis, was prepared from the prochiral molecule 6 , through the action of the lipase from Candida cylindracia . Approaches to novel enantiomeric and diastereoisomeric dideoxynucleosides containing the tetrahydrofuranethanol moiety have also been discovered. A key intermediate in this approach was the optically active trans-allyllactone 61 , prepared from L-glutamic acid, and its isomerization product, the corresponding cis-allylbutyrolactone 62 . The methodologies developed have generality and allow synthetic access to a wide variety of new nucleosides.

Synthetic approaches to novel isomeric dideoxynucleosides containing a chiral furanethanol carbohydrate moiety

Abstract Synthetic approaches to novel chiral dideoxynucleosides containing a furanethanol carbohydrate moiety have been developed. The key steps in these syntheses were the stereoselective preparation of the trans -allylbutyrolactone 5 , its conversion to the deoxygenated allyl sugar 8 , and its facile base-catalyzed isomerization to the cis -allylbutyrolactone 6 . These synthetic developments allow access to chiral isomeric dideoxynucleosides of both the purine and pyrimidine families.

Novel isomeric dideoxynucleosides of the D- and L-apiose family

Short synthetic approaches to optically active, cis and trans dideoxynucleoside analogs of the D- and L-apiose family have been developed. The chiral precursor for the syntheses was the enzymatically prepared compound, S(-)-2-(2-propenyl)-1,3-propanediol monoacetate (5).

Copper mediated reactions in nucleoside synthesis

Abstract The regiospecific functionalization of the base moiety of purine nucleosides through copper-mediated nucleophilic reactions is described.

Synthesis of congeners of adenosine resistant to deamination by adenosine deaminase

The novel metal-mediated syntheses of adenosine deaminase resistant congeners of adenosine are described.

Base-Transposed Chiral Isomeric Nucleosides

Abstract The synthesis and anti-HIV activities of a number of new analogues of basetransposed chiral isomeric nucleosides are described. Modifications of the anti-HIV active compound, (S,S)-isodideoxyadenosine, included both the base and carbohydrate regions.

Metal Mediated Reactions in Nucleside Synthesis

Abstract The reaction of a halogenated nucleoside with cuprous ions and appropriate nucleophiles allows for the introduction of a wide range of functional groups or synthons into specific postions of the base molety of nucleosides.