Synthesis and anti-HIV activity of 4'-thio-2',3'-dideoxynucleosides

Abstract

A series of 2',3'-dideoxy-4'-thionucleoside analogues of purines and pyrimidines, including 4'-thioddI (17), 4'-thioddC (27), and 4'-thioAZT (34), were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV). A stereospecific synthesis of the 2,3-dideoxy-4-thioribofuranosyl carbohydrate precursor 11 starting with L-glutamic acid is described. 2',3'-Dideoxy-4'-thiocytidine (27) displayed significant, but modest activity in vitro against human immunodeficiency virus.

Antiviral activities of isometric dideoxynucleosides of D- and L-related stereochemistry

“…1) related to natural Dnucleosides have been accomplished by Secrist et al (77). The results of anti-HIV activity studies are presented in Table 1.…”

The Properties of 4′‐Thionucleosides

“…Purine nucleosides 106 and 111 showed slight activity against HIV replication in MT-2 and CEM cells, in comparison with azathionine (AZT) and 2 0 ,3 0 -dideoxycytidine (DDC) ( Table 8.8) [18].…”

“…A series of 2 0 ,3 0 -dideoxy-4 0 -thionucleoside analogues of purines and pyrimidines such as 4 0 -thioddI (105), 4 0 -thioddC, and 4 0 -thioAZT were synthesized and evaluated for their activity against HIV [18]. The synthesis was carried out as follows: the starting compound 96 was prepared via 95 in three steps from L-glutamic acid, using known methodology [19].…”

Stereospecific Synthesis of Chiral 2,3‐Dihydro‐1,4‐benzodithiine and Methyl‐2,3‐dihydro‐1,4‐benzodithiine Derivatives and their Toxic Effects on Trypanosoma brucei

“…For example, bisdithiocarbamate derivatives of carbohydrates possess antifungal activity; [1] thiodeoxy nucleoside analogues in which the ring oxygen atom is replaced by a sulfur atom exhibit antiviral, antibacterial, and antitumor activities; [2,3] 5-thio-d-glucopyranose inhibits the transport of d-glucose and release of insulin; [4] 4'-thio-2',3'-dideoxynucleosides show in vitro activity against HIV; [5] and 2,2'-anhydro-4'-thio-1-b-d-arabinofuranosylcytosine has a comparable antitumor activity to 1-b-d-arabinofuranosylcytosine, which is used clinically against acute leukemia and lymphoma. [6] Non-carbohydrate organic compounds that contain a benzodithiine moiety have been reported to possess interesting antiviral activities.…”