Oxetanocin antiviral activity

Oxetanocin oxetanocinA, 9-[(2/ ,3/ ,45)-3,4-bis-(hydroxymethyl)-2-oxetanyl]adenine. CioHijNgOj, Mr 251.24, needles (XH2O), mp. 197 °C, [a]g> -44.3° (pyridine), a nucleoside antibiotic from culture broths of Bacillus megaterium exhibiting antibacterial and potent antiviral activities. In the name O. A the A is in-... 

However, in spite the interesting antiviral activity shown by oxetanocins, studies on their biosynthesis were limited since the oxetanocin A productivity of the strain was very low and unstable. Mutants producing high quantities of oxetanocin A were isolated from the original B. megaterium strain NK84-0228, but the productivities... 

The cyclobutyl nucleosides (149) have been prepared they are related structurally to carbocyclic oxetanocin analogues of known antiviral activity (Vol. 23, p. 197-8), but were inactive.2 3 Other references to oxetanocin analogues are given in Chapter 19. 

Except for the oxetanocin G analogue 22, carbocyclic 7-deazaguanosines do not seem to provide a fruitful source of potential antiviral agents. This obs ation agrees with others who have noted decreases in antiviral activity when carbocyclic 7-deazapurine nucleosides are compared to their purine parent systems. This correlation carries over into the cytotoxicity results in that the carbocyclic 7-deazaguanosines reported hoein showed no cytotoxicity, which is in contrast to what is often seen in the 7-deaztq)urine nucleoside series. 

The naturally occurring oxetanocin A (18) and synthetic oxetanocin G (19) represent a novel class of nucleosides possessing antiviral propmies. Modification of die unique oxetanosyl-lV-glycoside structural feature of 18 and 19 into the carbocyclic nucleoside framework led to the synthesis of 20 and 21 as racemates and enantiomers, which have shown activity against herpesviruses and HIV.22b,c,24,25 in view of the potent and selective anti-HCMV properties of the l -enantiomer of 21, the synthesis of the R sto eoisomer 22 was undertaken and accomplished. 

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