150943-17-2Relevant academic research and scientific papers
Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally "frozen" analogues of L-glutamic acid
Bechi, Beatrice,Amantini, David,Tintori, Cristina,Botta, Maurizio,Di Fabio, Romano
, p. 1114 - 1120 (2014/06/09)
Several strategies aimed to "freeze" natural amino acids into more constrained analogues have been developed with the aim of enhancing in vitro potency/selectivity and, more in general, drugability properties. The case of L-glutamic acid (L-Glu, 1) is of particular importance since it is the primary excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a critical role in a wide range of disorders like schizophrenia, depression, neurodegenerative diseases such as Parkinson's and Alzheimer's and in the identification of new potent and selective ligands of ionotropic and metabotropic glutamate receptors (GluRs). To this aim, bicycle compound Ib was designed and synthesised from D-serine as novel [2.3]-spiro analogue of L-Glu. This frozen amino acid derivative was designed to further limit the rotation around the C3-C4 bond present in the azetidine derivative Ia by incorporating an appropriate spiro moiety. The cyclopropyl moiety was introduced by a diastereoselective rhodium catalyzed cyclopropanation reaction.
Total synthesis of polyoximic acid
Hanessian, Stephen,Fu, Jian-Min
, p. 1812 - 1826 (2007/10/03)
The structure and stereochemistry of polyoximic acid, a degradation product of polyoxins, was originally designated as trans-3-ethylidene-L-azetidine-2-carboxylic acid. However, total synthesis revealed that the correct structure was in fact cis-3-ethylidene-L-azetidine-2-carboxylic acid, which was confirmed by X-ray crystallography. The synthesis of the trans-isomer was also done and its identity was confirmed by X-ray analysis as well. The key step for constructing the four-membered ring was a rhodium catalyzed carbenoid insertion into the N - H bond of a β-amino acid derivative. The stereoselectivity of the exo-double bond was controlled by conducting a Horner-Emmons-Wadsworth or a Wittig reaction to generate the trans- and cis-isomers, respectively. Weinreb's amide was used as a latent methyl group for the separation of trans and cis mixtures. The double bond stereochemistry of polyoximic acid in the parent polyoxin was also confirmed to be cis by extensive 2D NMR studies.
TOTAL SYNTHESIS OF (+)-POLYOXIMIC ACID - CIS-3-ETHYLIDENE-L-AZETIDINE-2-CARBOXYLIC ACID
Hanessian, Stephen,Fu, Jian-Min,Chiara, Jose-Luis,Fabio, Romano Di
, p. 4157 - 4160 (2007/10/02)
The stereocontrolled total synthesis of (natural) cis- and (unnatural) trans-polyoximic acids is described starting with D-serine as a chiral template.
