Synthesis of carbocyclic oxetanocin analogs bearing fluorine and their antiviral activities.
A new procedure to introduce the fluorine into the carbocycle of carbocyclic oxetanocin in A (C.OXT-A) was developed. The cyclobutanols 5 and 10, obtainable from the 2,3-di-O-benzoate 3, were condensed with 6-chloropurine using Mitzunobu reaction to give the cyclobutyl nucleosides 6 and 11, respectively. Addition of iodine fluoride to compound 6 afforded [(1R*,2S*,3R*)-isomer 7 as a sole addition product, which was converted to 1. This compound (1) exhibited a broad spectrum of antiviral activity, especially against human cytomegalovirus. Also partial depretection of 11 and successive fluoridation using DAST gave the fluoromethyl derivatives from which another target compounds 2a,b were obtained.
Sato
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Maruyama
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D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects; D005461:Fluorine / Q000737:chemistry; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008722:Methods; D015394:Molecular Structure
D000998:Antiviral Agents; C051061:oxetanocin; D005461:Fluorine; D000225:Adenine