Conformationally restricted glutamic acid analogues: stereoisomers of 1-aminospiro[3.3]heptane-1,6-dicarboxylic acid

All four stereoisomers of the title compound (1a-d) were prepared, starting from a common precursor, 3-oxocyclobutanecarboxylic acid. Lewis acid-catalyzed rearrangement of a 8-oxadispiro[2.0.3.1]octane-6-carboxylic acid derivative was used as the key synthetic step to construct the suitably functionalized spiro[3.3]heptane skeleton. A stabilized oxaphosphetane intermediate of the Wittig reaction was detected along the synthetic route. Separation of the diastereomeric intermediates allowed each target compound to be obtained as a single stereoisomer. The target compounds are all analogues of the glutamic acid; they mimic glutamate in a large array of restricted conformations, which might be used in mechanistic studies or in a systematic search for biologically active compounds.

Chernykh A. V.; Radchenko D. S.; Grygorenko O. O.; Volochnyuk D. M.; Shishkina S. V.; Shishkin O. V.; Komarov I. V.
RSC Adv. 2014, 4 (21), 10894-10902
DOI: 10.1039/C3RA47725H