SYNTHESIS OF CARBOCYCLIC ANALOGS OF 1-BETA-D-PSICOFURANOSYL NUCLEOSIDES - PSICO-CYCLOPENTENYLADENOSINE (PSICOPLANOCIN-A) AND PSICO-CYCLOPENTENYLCYTOSINE

Psicoplanocin A (4a) and psico-cyclopentenylcytosine (4b) represent th e first two known examples of carbocyclic ketohexose nucleosides. Thes e two stable compounds combine structural features of two known classe s of natural products: neplanocin A and the ketohexose nucleosides psi cofuranine (1a) and decoynine (2). Both compounds were synthesized in racemic form from (+/-)-cyclopentenone 5, which in turn was available froM D-ribonolactone. Construction of the surrogate glycon moiety comm enced with the attachment of a protected hydroxymethyl fragment onto t he ketone carbonyl of 5 via nucleophilic addition of [(benzoyloxy)meth yl]lithium to give intermediate 7. Introduction of the requisite nitro gen at the tertiary allylic carbon of 7 was achieved by the BF3.OEt2-c atalyzed addition of hydrazoic acid to a generated transitional allyli c cation. This method produced the epimeric azides 8a and 8b, and foll owing conversion of the beta-azide (8a) to the corresponding carbocycl ic amine, the purine and pyrimidine rings of psicoplanocin A and psico -cyclopentenylcytosine were constructed by conventional methods. An X- ray crystallographic analysis corroborated the structure of psicoplano cin A determined from NOE experiments on the epimeric azides. Both psi coplanocin A and psico-cyclopentenylcytosine were found to be devoid o f cell cytotoxicity and in vitro antiviral activity.