Synthesis of 3'-alkylthio-2',3'-dideoxy nucleosides with potential anti-HIV activity from 2-deoxy-D-ribose, using a phosphorus pentoxide reagent.
Direct condensation of 2-deoxy-D-ribose (1) with mercaptans using the P4O10/H2O/Bu3N reagent in chloroform resulted in coupling at C-3 to give the anomeric mixtures of the corresponding pentopyranoses 2 and pentofuranoses 3. After acetylation with acetic anhydride in dry pyridine of these 3-alkylthio pentofuranoses, coupling with the nucleobases uracil, thymine, and cytosine in accordance with the Friedel-Crafts catalyzed silyl Hilbert-Johnson method yielded the acetylated D-erythro nucleosides 7 as anomeric mixtures, separable only by means of chromatography either before or after deprotection with ammonia. The nucleosides 8a-e were devoid of any activity against HSV-1 and HIV-1.
Dueholm
K L
KL
Department of Chemistry, Odense University, Denmark.
Motawia
M S
MS
Pedersen
E B
EB
Nielsen
C
C
Lundt
I
I
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003855:Deoxyribose / Q000737:chemistry; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects*; D006801:Humans; D007202:Indicators and Reagents; D010758:Phosphorus; D017553:Phosphorus Compounds; D018139:Simplexvirus / Q000187:drug effects
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D007202:Indicators and Reagents; D017553:Phosphorus Compounds; D010758:Phosphorus; C012500:phosphorus pentoxide; D003855:Deoxyribose