Asymmetric synthesis and translational competence of L-alpha-(1-cyclobutenyl)glycine

reaction: see text] L-alpha-(1-Cyclobutenyl)glycine (1-Cbg) was targeted as a potentially translatable analogue of isoleucine and valine and as a useful building block for peptides. An enantioselective synthesis was executed in which the key step was diastereoselective addition of 1-cyclobutenylmagnesium bromide to the sulfinimine 2b derived from (S)-t-butanesulfinimide and tert-butyl glyoxylate. 1-Cbg was found to substitute efficiently for isoleucine and valine, but not leucine, in the translation of green fluorescent protein in vitro.