Abstract: An efficient process for the deoxygenation of 2'- and or 3'-hydroxyl groups of a nucleoside that includes reacting the hydroxyl group with 3-halopropionitrile or 2-nitroethylhalide and carbon disulfide in base to form a 2'- or 3'-(cyanoethylthio or nitroethylthio)thiocarbonyl, that is reductively eliminated and replaced with hydrogen. The deoxygenation process can be used in a wide variety of nucleoside syntheses that require the elimination of the 2'- or 3'-hydroxyl groups, including the preparation of 3'-substituted-2',3'-dideoxynucleosides such as 3'-azido-3'-deoxythymidine and 3'-azido-2',3'-dideoxyuridine.

Abstract: An asymmetric process for the preparation of enantiomerically pure .beta.-L-(-)-1,3-oxathiolane-nucleosides that includes the initial preparation of the key chiral intermediates (2R,5R) and (2R,5S)-5-(O-protected)-2-(protected-oxymethyl)-1,3-oxathiolane from 1,6-thioanhydro-L-gulose. The 2R,5(R,S)-5-(O-protected)-2-(protected-oxymethyl)-1,3-oxathiolane is condensed with a desired heterocyclic base, typically a purine or pyrimidine base, to provide the product nucleoside. The synthesis can be used to prepare the pharmaceutically important compound, .beta.-L-(-)-1-[(2.beta.,4.beta.)-2-(hydroxymethyl)-4-(1,3-thioxolane)]cyt osine (.beta.-L-(-)BCH-189).

Abstract: The present invention are novel compounds of the formula: ##STR1## wherein R is OH, NH.sub.2, OW, or H; X is H, F, Cl, Br, I, OH, OW, NO.sub.2 or NH.sub.2 ; Y is H, F, Cl, I, or Br; W is C(O)Z or a C.sub.1 to C.sub.12 alkyl group; Z is an aliphatic or aromatic group of from C.sub.1 to C.sub.12 ; X and Y can both vary within the molecule; and if R is H, at least one of X or Y is not H. In a preferred embodiment, R is OH or NH.sub.2. The most preferred compound is (4-hydroxy-3-N-phenylacetylamino-2,6-piperidinedione), in which R is OH, X is H and Y is H. These compounds have cytostatic activity and insert stereochemically into DNA.

Abstract: A method for the preparation of 2'-deoxynucleosides and 2',3'-dideoxy-2',3'-didehydronucleosides that includes the step of reacting a nucleoside having hydroxyl groups in the 2' and 3' positions with a mixture of acyl bromide or chloride and HX, wherein X is Br or Cl, at moderate temperature, to give a haloacyl nucleoside derivative that can be deprotected and reduced to form the desired compound.

Abstract: A pharmaceutical composition in dosage unit form comprising a therapeutically effective HIV inhibitory amount of a compound having the formula: ##STR1## wherein R.sup.1 is selected from the group consisting of OH, C.sub.1-4 acyl, sulfate phosphate, and amino; R.sup.2 is O or NH, and R.sup.3 C or N, or a pharmacologically acceptable acid addition salt thereof, in association with a pharmaceutical carrier.

Abstract: An asymmetric process for the preparation of enantiomerically pure .beta.-D-(-)-dioxolane-nucleosides. The enantiomerically pure dioxolane nucleosides are active HIV agents, that are significantly more effective than the prior prepared racemic mixtures of the nucleosides. The anti-viral activity of the compounds is surprising in light of the generally accepted theory that moieties in the endo conformation, including these dioxolanes, are not effective antiviral agents. The toxicity of the enantiomerically pure dioxolane nucleosides is lower that that of the racemic mixture of the nucleosides, because the nonnaturally occurring .alpha.-isomer is not included.The product can be used as a research tool to study the inhibition of HIV in vitro or can be administered in a pharmaceutical composition to inhibit the growth of HIV in vivo.

Abstract: A method of preparation of 2',3'-dideoxy and 2',3'-dideoxy-2',3'-didehydronucleosides that includes the step of condensing a 1-O-activated-2-(aromatic or aliphatic)-selenenyl-5-O-protected ribose with a protected heterocyclic base in the presence of trimethylsilyl triflate or a Lewis acid to form a .beta.-anomeric nucleoside in high yield.

Abstract: This invention provides compounds and pharmaceutical compositions that include compounds of the formula: ##STR1## in which A, B, and C are hydrogen, halogen, or azido; D is hydrogen, halogen, azido, or OH; A and B or C and D can be replaced with a double bond; R is an aldohexose, aldohexosamine, or N-acetyl aldohexosamine, W is O or S; X is O, S, or CH.sub.2 ; Y is a purine or pyrimidine base, Z is C, S, or O, and wherein when Z is S or O, A and C are not present. The compounds of this inverntion have enhanced pharmaceutical or biological activity or increased intracellular absorption compared to the corresponding parent nucleoside as a function of the 5'-diphosphohexose moiety. Many of these compounds have antiviral, including anti-HIV, activity. Others have antibacterial activity. In one embodiment, the invention is a method to treat HIV infection and opportunistic infections concomitantly.

Abstract: The present invention is an antiviral composition which includes a means and method for delivering an HIV-inhibitory amount of an active compound of the general formula: ##STR1## wherein R is OH, monophosphate, diphosphate, or triphosphate, or a pharmacologically acceptable salt thereof; and wherein the means is a pharmaceutically acceptable carrier. In the preferred embodiment, an effective dose of 3'-azido-2',3'-dideoxy-5-methylcytidine, or its derivatives is administered in a pharmaceutically acceptable carrier to a patient for the treatment of AIDS.

Abstract: A composition delivering an HIV-inhibitory amount of an active compound of the general formula: ##STR1## wherein R is OH, monophosphate, diphosphate, or triphosphate, or a pharmacologically acceptable salt thereof; and wherein the means is a pharmaceutically acceptable carrier. In the preferred embodiment, an effective dose of 3'-azido-2',3'-dideoxy-5-methylcytidine, or its derivatives, is administered in a pharmaceutically acceptable carrier to a patient for the treatment of AIDS.

Abstract: A general method of synthesis of 2',3'-dideoxynucleosides which is efficient, inexpensive and based on a readily available starting material, D-mannitol.

Abstract: 2'-Deoxy-2'-fluoro-.beta.-D-arabinofuranosyl nucleosides of the following structure are disclosed: ##STR1## wherein X and Y are the same or different and are hydrogen, OR.sup.3, SR.sup.3, NR.sup.3 N.sup.4 or NHacyl wherein R.sup.3 and R.sup.4 are the same or different and are hydrogen, lower alkyl of 1 to 7 carbon atoms, aralkyl, or aryl;NHacyl is alkanoyl or aroylamide;R.sup.1 and R.sup.2 are the same or different and are hydrogen, acyl or aroyl.

Abstract: Compositions for the treatment of AIDS and ARC having the following compound as an active ingredient: ##STR1## where R.sup.1 is OH, monophosphate, diphosphate, or triphosphate; or a pharmacologically acceptable salt thereof.The primary advantage of this compound is its highly selective anti-retroviral activity, i.e., it significantly decreases viral replication as measured as reverse transcriptase activity while demonstrating orders of magnitude less cytotoxicity than other anti-viral compounds such as AZT.In a preferred embodiment, the compound is present in an amount sufficient to inhibit the HIV reverse transcriptase activity but not significantly inhibit human DNA polymerase activity. Also included within the scope of this invention are 3'-azido-2',3'-dideoxyuridine mono-, di-, and triphosphate and compositions containing these compounds as the active agent.

Abstract: A compound which exhibits antiviral activity towards HTLV-III/LAV, having the formula: ##STR1## wherein R.sup.4 is O or NH;R.sup.5 is a C.sub.2-4 alkyl group or a C.sub.3-4 cycloalkyl group, whereinsaid alkyl group or cycloalkyl group may be substituted by one or more of Cl, Br, I, F, OH, N.sub.3, NH.sub.2, SO.sub.3 H, or COOH;R.sup.6 is hydrogen or a C.sub.1 -C.sub.4 alkyl group, which may be substituted by Cl, Br, I, F, OH, N.sub.3, NH.sub.2, SO.sub.3 H, or COOH;R.sup.3' is N.sub.3, NH.sub.2, or H; and R.sup.5' is N.sub.3, NH.sub.2, OH, phosphate, or a C.sub.1-4 acyl group.

Abstract: 2'-Deoxy-2'-fluoro-.beta.-D-arabinofuranosyl nucleosides of the following structure are disclosed: ##STR1## wherein X and Y are the same or different and are hydrogen, OR.sup.3, SR.sup.3, NR.sup.3 R.sup.4 or NHacyl wherein R.sup.3 and R.sup.4 are the same or different and are hydrogen, lower alkyl of 1 to 7 carbon atoms, aralky, or aryl;NHacyl is alkanoyl or aroylamide;R.sup.1 and R.sup.2 are the same or different and are hydrogen, acyl or aroyl.

Abstract: A compound which exhibits antiviral activity towards HTLV-III/LAV, having the formula: ##STR1## wherein R.sup.4 is O or NH; R.sup.5 is a C.sub.2-4 alkyl group or a C.sub.3-4 cycloalkyl group, wherein said alkyl group or cycloalkyl group may be substituted by one or more of Cl, Br, I, F, OH, N.sub.3, NH.sub.2, SO.sub.3 H, or COOH; R.sup.6 is hydrogen or a C.sub.1 -C.sub.4 alkyl group, which may be substituted by Cl, Br, I, F, OH, N.sub.3, NH.sub.2, SO.sub.3 H, or COOH; R.sup.3' is N.sub.3, NH.sub.2, or H; and R.sup.5' is N.sub.3, NH.sub.2, OH, phosphate, or a C.sub.1-4 acyl group.

Abstract: There is provided a novel process for pyrimidine to pyrimidine transformations by the displacement of the 1,2,3-portion of a pyrimidine by a 1,3-ambident nucleophile. The novel process requires that the 1 and 3 nitrogens of the pyrimidine moiety be substituted. The novel process makes available, inter alia, novel uracils, simple methods of radioisotopically labeling pyrimidine nuclei, a simple and inexpensive method of preparing the important antiviral and antileukemic material pseudoisocytidine and its new active analog 2'-deoxypseudoisocytidine.

Abstract: Pseudo-isocytidine is disclosed as well as methods and intermediates useful in its preparation. The novel compound pseudo-isocytidine, preferably the beta-anomer thereof, is an active cytostatic and anti-leukemic agent.