Synthesis and antiviral activity of 3'-C-branched-3'-deoxy analogues of adenosine.
The synthesis of some 3'-C-branched-3'-deoxy adenine nucleosides is described. Starting from the known 3-deoxy-3-C-(hydroxymethyl)-1,2;5,6-di-O-isopropylidene-alpha-D-allof uranose (1), a versatile glycosylating agent, namely 1,2-di-O-acetyl-5-O-benzoyl-3-deoxy-3-C-(mesyloxymethyl)-beta-D-ri bofuranose (6), was prepared in three steps. Condensation of the latter with bis(trimethysilylated) N6-benzoyladenine in the presence of tin(IV) chloride gave the N9-beta-nucleoside 7. Compound 7 was converted into (i) 9-[3-C-(azidomethyl)-3-deoxy-beta-D-ribofuranosyl]adenine (10), (ii) 9-[3-C-(azidomethyl)-2,3-dideoxy-beta-D-glycero-pent-2-enofuran osyl]adenine (14) and 9-[2-azido-3-C-(azidomethyl)-2,3-dideoxy-beta-D-arabinofuranosyl]a denine (15), and (iii) 9-[3-deoxy-2-O,3-C-(methylene)-beta-D-ribofuranosyl]adenine (16). None of the tested nucleosides showed marked cytostatic or antiviral activity in vitro.
Mikhailopulo
I A
IA
Institute of Bioorganic Chemistry, Byelorussian Academy of Sciences, Byelorussia.
Poopeiko
N E
NE
Tsvetkova
T M
TM
Marochkin
A P
AP
Balzarini
J
J
De Clercq
E
E
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002942:Circular Dichroism; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology; D014780:Viruses / Q000187:drug effects*
D000998:Antiviral Agents; D003839:Deoxyadenosines; D009705:Nucleosides