Synthesis of cyclobutane nucleoside analogues 3: Preparation of carbocyclic derivatives of oxetanocin

Abstract

A synthesis of cyclobutene nucleoside analogs in which the nucleobase is tethered by a methylene group is described. The coupling of 6-chloropurine with 3-hydroxymethyl-cyclobutanone proceeds via its triflate to give both N-7 and N-9 regioisomers with relative yields corresponding to the calculated charge distribution of the 6-chloropurinyl anion. The stereoselective reduction of the N-alkylated ketones yielded quantitatively one stereoisomer in each case. The structural assignments were based on spectroscopic data and single crystal X-ray diffraction. Attempts to photoexcite the N-7 and N-9 ketones in order to promote ring-expansion did not ensue. Preliminary evidence suggests a photodecarbonylation to cyclopropanes took place.

Synthesis of Cyclobutane Analogue 4: Preparation of Purine and Pyrimidine Carbocyclic Nucleoside Derivatives

“…We have already described the coupling of 6-chloropurine to the C-2 position and the C-3 position by a methylene pendant in recent publications [14,15]. In the current study we report on the coupling reactions of the parent purine nucleobase to the C-2 position of 3-hydroxylmethylcyclobutanol, and the coupling reactions of pyrimidine bases to a methylene bridged C-3 cyclobutanol.…”

“…We reported recently on the 6-chloropurine N- alkylation to 3-hydroxymethylcyclobutanone triflate 10 [15]. In order to complete the series of these related nucleoside analogs we undertook to couple the pyrimidine nucleobases thymine and uracil with ketone 10 .…”