A new nucleophilic ring opening of an activated cyclopropane and a formal synthesis of (+/-)-carbovir.
The reaction of bicyclo[3.1.0]hexane 1, possessing a doubly activated cyclopropane ring, with acetic acid and potassium acetate in DMSO proceeded smoothly to give the adduct 2 in good yield. A formal total synthesis of the potent anti-HIV agent (+/-)-carbovir (9) was done by converting 2 into a known precursor 8 in 8 steps via allyl alcohol 7 including the regioselective introduction of a double bond (4 to 5) and attachment of the nucleobase using the Mitsunobu reaction (7 to 8).
Department of Applied Biochemistry, College of Agriculture, Osaka Prefecture University, Japan.
S
S
Tanimori
M
M
Tsubota
M
M
He
M
M
Nakayama
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003521:Cyclopropanes / Q000737:chemistry*; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
D000998:Antiviral Agents; D003521:Cyclopropanes; D015224:Dideoxynucleosides; C057503:carbovir; C030797:cyclopropane