Synthesis and antitumor activity of phenyl carbocyclic oxetanocin and related compounds

Reaction of trans-2,3-bis[(tert-butyldimethylsilyl)oxymethyl] -1-cyclobutanone (4a) with phenylmagnesium bromide or lithiated aromatic compounds gave two adducts, the (1R, 2R, 3R) isomers (5a--c) and the (1R,2S,3S) isomers (6a--c). The major products (5a, c) were treated with tetrabutylammonium fluoride to give the (1R,2R,3R)-1-aryl-2,3-bis(hydroxymethyl)-1-cyclobutanols (1a, c). The 3-(oxazol-2-yl)-phenyl adduct 5b was converted to the benzamide congener 1b in 6 steps. On catalytic reduction of 1a with Raney Ni the stereochemistry at C-1' was mostly retained, but in the case of 10% Pd-C catalyst, steric inversion occurred. Compounds 1a-c displayed no cytotoxicity towards human nasopharyngeal carcinoma KB cell line.