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Bicyclic glutamic acid derivatives
Author(s) -
Meyer Udo,
Bisel Philippe,
Weckert Edgar,
Frahm August Wilhelm
Publication year - 2006
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20260
Subject(s) - diastereomer , chemistry , bicyclic molecule , enantiomer , strecker amino acid synthesis , hydrogenolysis , chirality (physics) , stereochemistry , chiral auxiliary , amino acid , enantiomeric excess , hydrolysis , nitrile , organic chemistry , enantioselective synthesis , catalysis , biochemistry , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
For the second‐generation asymmetric synthesis of the trans ‐tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric α‐amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H 2 SO 4 yielding diastereomeric mixtures of three secondary α‐amino α‐carbamoyl‐γ‐esters and two diastereomeric cis ‐fused angular α‐carbamoyl γ‐lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis ‐α‐amino α‐carbamoyl‐γ‐esters. Separation was achieved by CC. The pure secondary trans ‐α‐amino α‐carbamoyl‐γ‐esters cyclise on heating and treatment with concentrated H 2 SO 4 , respectively, to diastereomeric cis ‐fused angular secondary α‐amino imides. Their hydrogenolysis led to the enantiomeric cis ‐fused angular primary α‐amino imides. The configuration of all compounds was completely established by NMR methods, CD‐spectra, and by X‐ray analyses of the (α R ,1 R ,5 R )‐1‐carbamoyl‐2‐(1‐phenylethyl)‐2‐azabicyclo[3.3.0]octan‐3‐one and of the trans ‐α S ,1 S ,2 R ‐2‐ethoxycarbonylmethyl‐1‐(1‐phenylethylamino)cyclopentanecarboxamide. Chirality, 2006. © 2006 Wiley‐Liss, Inc.