5'-substituted ribofuranosyl nucleosides

Abstract

Abstract NOVEL (5-SUBSTITUTED-5-DEOXYRIBOFURANOSYL)-PURINES AND PYRIMIDINES WHERE THE 5-SUBSTITUENT IS ACETYLTHIO, THIOCYANO, AZIDO, ALKYLAMINO, OR FLUORO, ARE PREPARED BY REACTION OF A (2,3-O-ISOPROPYLIDENE-5-O-TOSYLRIBOFURANOSYL)-PURINE OR PYRIMIDINE WITH AN ALKALI METAL THIOACETATE, THIOCYANATE, AZIDE, ALKYLAMINO, OR FLUORIDE, RESPECTIVELY. THE 5''-AZIDO-GROUP IS THEN HYDROGENATED TO A 5''-AMINO-GROUP. THE (5''-AMINO-5-DEOXY-2,3-O-ISOPROPYLIDENE-RIBOFURANOSYL) PURINE OR PYRIMIDINE IS THEN REACTED WITH AN ALKANOYL HALIDE OR ANHYDRIDE, ADAMATOYL HALIDE, ETHYL CHLOROFORMATE OR POTASSIUM CYANATE TO PRODUCE THE CORRESPONDING 5-ALKANOYLAMINO, ADAMANTOYLAMIDO, N-CARBOETHOXYAMINO, UREIDO, OR CYANAMIDO-DERIVATIVE, RESPECTIVELY. THE 5-CYANAMIDO-DERIVATIVE IS FURTHER REACTED WITH AMMONIA IN AN AMINE TO GIVE THE CORRESPONDING 5GUANIDINO DERIVATIVE. THE PURINE DERIVATIVES MAY BE SUBSTITUTED AT THE 2,6-POSITIONS OF THE PURINE NUCLEUS AND THE PYRIMIDINE DERIVATIVES (E.G. CYTIDINE OR URIDINE) MAY BE SUBSTITUTED AT THE 5-POSITION OF THE PYRIMIDINE NUCLEUS. THE (5-SUBSTITUTED-5-DEOXYRIBOFURANOSYL)-PURINES, AND PYRIMIDINES HAVE ANTIVIRAL ACTIVITY AGAINST HERPES, VACCINIA AND ADENO II VIRUSES, AND ARE ALSO USEFUL IN VITIO AS NUCLEOSIDE ANTIMETABOLITES, AND AS NUCLEIC ACID BIOSYNTHESIS INHIBITORS.

Inventors

• 👤 Tsung-Ying Shen
• 👤 William V Ruyle
• 👤 Thomas Neilson

Bibliographic Details