Amino substituted derivatives of 5'-amino-5'-deoxy-5'-noraristeromycin.
The potent antiviral potential of 5'-amino-5'-deoxy-5'-noraristeromycin (2) is limited by associated toxicity. To seek derivatives of 2 that circumvent this undesirable property, three amino substituted derivatives (acetyl, 3; formyl, 4; and methyl, 5) of 2 have been prepared in 4-7 steps from the same intermediate, (1S,4R)-4-(6-chloropurin-9-yl)cyclopent-2-en-1-ol (6). Key steps involved an improved Pd(0)-catalyzed allylic azidation and a novel Pd(0)-catalyzed allylic amidation. The three target compounds were evaluated against a large number of viruses and found to be inactive except for a very weak effect of 5 on human cytomegalovirus, varicella zoster virus, and Epstein-Barr virus. There was also no noteworthy cytotoxicity associated with the new derivatives. Thus, these results indicate variation of the cyclopentyl amine of 2 does not offer a means to improve upon its antiviral potential.
Yang
Minmin
M
Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA.
Schneller
Stewart W
SW
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests
C502760:5'-amino-5'-deoxy-5'-noraristeromycin; D000998:Antiviral Agents; D000241:Adenosine