Enantioselective Synthesis of l-CCG-I

Abstract

Introduction of natural menthol as the chiral auxiliary in a gamma-Br-alpha,beta-unsaturated ester leads to enantioselective generation of three chiral centers in a single step on reaction with a glycine anion equivalent to provide L-CCG-I in 94% ee.

Natural Occurrence, Syntheses, and Applications of Cyclopropyl-Group-Containing α-Amino Acids. 2. 3,4- and 4,5-Methanoamino Acids

“…Successive acid-and base-catalyzed hydrolysis of the ester and Schiff-base functionalities led to enantiomerically pure L-CCG-I (2S,1′S,2′S)-127 (Scheme 30). 102 In contrast, an analogous MIRC reaction carried out with an (R)-camphor-derived imine of tert-butyl glycinate and methyl (2E)-4-bromobut-2-enoate gave a mixture of four, only partially separable diastereomers of the corresponding cyclopropyl derivative. 103 Different diastereomeric (2-carboxycyclopropyl)glycines in enantiopure form have played an important role in a variety of pharmacological investigations and studies concerning the involvement of the neurotransmitter L-glutamate and glutamate receptors in integrative brain functions of the mammalian central nervous system (CNS).…”

“…A Michael-induced ring closure (MIRC) reaction of the glycinate enolate generated from ethyl (diphenylmethyleneamino)acetate ( 176 ) with the enantiopure (−)-menthyl 4-bromocrotonate ( 175 ) furnished the cyclopropane derivative 177 as a single diastereomer. Successive acid- and base-catalyzed hydrolysis of the ester and Schiff-base functionalities led to enantiomerically pure l -CCG-I (2 S ,1‘ S ,2‘ S )- 127 (Scheme ) …”

Total Syntheses of (+)-α-Allokainic Acid and (−)-2-epi-α-Allokainic Acid Employing Ketopinic Amide as a Chiral Auxiliary

“…However, diastereoselectivity for the longer β-alkyl-substituted Michael acceptor remains to be improved . Michael reaction of iminoglycinate with α,β-unsaturated esters by chiral auxiliaries had also been reported . It had been reported that α-functionalization of iminoglycinate employing ketopinic acid as an auxiliary via a dianionic enolate gave a poor diastereoselectivity .…”

Allylic Alkylation versus Michael Induced Ring Closure: Chelated Enolates as Versatile Nucleophiles

“…This makes the domino reactions highly attractive for natural product synthesis and related applications . The Michael induced ring closing reactions (MIRC) play a dominant role in this field of chemistry and many synthetic applications are described in the literature so far. , Toward the synthesis of natural and unnatural amino acids, e.g., the lithium enolates of O'Donnell's phenylimino glycin esters can be used, as illustrated with several syntheses of cyclopropyl glycines .…”