Mohammed S. Motawia

Synthesis of 5-dialkylaminomethyl-3′-azido and 3′-fluoro-2′,3′-dideoxyuridines for evaluation as anti-HIV agents

SummaryUracil (8) was substituted in a Mannich reaction to give the 5-substituted dialkylamino-methyluracils11a–f in 65–85% yield. Compounds11a–f were silylated with hexamethyldisilazane and coupled with 2,3-dideoxy-3-fluoro-D-erythro-pentofuranoside4 and 3-azido-2,3-dideoxy-D-erythro-pentofuranoside7 to give the corresponding 3′-fluoro-2′,3′-dideoxynucleosides13a–f and 3′-azido-2′,3′-dideoxy nucleosides16d, f, respectively, by using trimethylsilyl trifluoromethanesulfonate as a catalyst. Deprotection of the 5-O-(4-phenylbenzoyl) protected nucleosides13a–f and16d, f with saturated methanolic ammonia and separation by chromatography yielded the new derivatives of 2′,3′-dideoxy-3′-fluorouridines14a–f and15a–f and 2′,3′-dideoxy-3′-azidouridines17d, f and18d, f.ZusammenfassungAus Uracil (8) wurden in einer Mannich-Reaktion in 65–85% Ausbeute die 5-substituierten Dialkylaminomethyluracile11a–f hergestellt. Verbindungen11a–f wurden mit Hexamethyldisilazan silyliert und mit 2,3-Didesoxy-3-fluor-D-erythro-pentofuranosid (4) und 3-Azido-2,3-didesoxy-D-erythro-pentofuranosid (7) unter Verwendung von Trimethylsilyl-trifluormethansulfonat als Katalysator zu den entsprechenden 3′-Fluor-2′,3′-didesoxynucleosiden13a–f und 3′-Azido-2′,3′-didesoxynucleosiden16d, f umgesetzt. Deprotektion der 5-O-(4-Phenylbenzoyl)- geschützten Nucleoside13a–f und16d, f mit gesättigtem methanolischem Ammoniak und Trennung mittels Chromatographie ergab die neuen 2′,3′-Didesoxy-3′-fluoruridine14a–f und15a–f, sowie die 2′,3′-Didesoxy-3′-azidouridine17d, f und18d, f.

New route for the synthesis of 2-thiouracil analogues of 3′-azido-2′,3′-dideoxy nucleosides

SummaryReaction of 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranoside (5) with silylated 2-thiouracil and 5-alkoxy-2-thiouracils in the presence of trimethylsilyl trifluoromethanesulfonate afforded an anomeric mixture of the corresponding 3′-azido-2′,3′-dideoxy-2-thiouridine derivatives with the α-anomer as the main product. Deprotected nucleosides were obtained by treatment with tetrabutylammonium fluoride.ZusammenfassungDie Reaktion von 3-Azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranosid (5) mit silyliertem 2-Thiouracil und 5-Alkoxy-2-thiouracil in Gegenwart von Trimethylsilyltrifluormethansulfonat ergab eine anomere Mischung der entsprechenden 3′-Azido-2′,3′-dideoxy-2-thiouridin-Derivate, wobei das α-Anomer das Hauptprodukt darstellte. Die ungeschützten Nucleoside wurden mittels Behandlung mit Tetrabutylammoniumfluorid erhalten.

Thio Nucleoside Derivatives as Intermediates or Target Compounds in the Attempt of Finding New Agents Against HIV

Abstract 3′-Alkylthio-2′-,3′-dideoxy nucleosides and D4T are synthesized. An attempt of synthesizing a hybrid between AZT and HEPT is presented.

2,3-Dideoxy-3-Phthalimidopentoses in the Synthesis of 3'-Amino-2',3'-Dideoxynucleosides

Abstract 3′-Amino-3′deoxythymidine is a very effective drug in vivo against L 1210 leukemia. It mives 1441 increase in lifespan with very little drug-induced toricitylil. Therefore, it was attractive to synthesize a large series of cuialogues, but unfortunately, such compounds are only achievable through a 1inear synthesis via the corresponding nucleoside which typically is transformed into the 3′-azido derivative and finally reduced.