An efficient method for the preparation of Boc-protected 4,5-methano-β-proline - a novel bicyclic cyclopropane-containing β-amino acid - was developed, starting from readily available itaconic acid. A modified Simmons-Smith reaction was used for the construction of the cyclopropane ring. The method allowed for the synthesis of both cis and trans isomers of the title compound in 49% total yield and can be employed for gram-scale preparations. An approach to the preparation of methyl 5-oxopyrrolidine-3-carboxylate, which is one of the key intermediates in the synthetic scheme, on a multigram scale was also developed.
Tymtsunik, Andriy V.,Ivon, Yevhen M.,Komarov, Igor V.,Grygorenko, Oleksandr O.
p. 3312 - 3315
(2014/06/09)
N-Hydroxy Amides. III. Active Esters of Polystyrene-bound 1-Hydroxy-2-pyrrolidinone and Their Use in Peptide Synthesis
A polymer-bond cyclic N-hydroxy amide has been prepared by reaction of aminomethylated copoly(styrene-2percent divinylbenzene) with 1-hydroxy-5-oxo-3-pyrrolidinecarboxylic acid using dicyclohexylcarbodiimide (DCC) as a condensing agent.Several N-blocked α-amino acids have been loaded on this resin by use of DCC.The amino acid resin can be utilized for peptide synthesis.Repetitive usage of the resin in the form of esters and facile synthesis of a biologically active pentapeptide, Leu5-enkephalin, show the usefulness of the polymer-bound 1-hydroxy-2-pyrrolidinone.