Bicyclic glutamic acid derivatives.
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 alpha-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 alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.
Meyer
Udo
U
Department of Pharmaceutical Chemistry, Albert-Ludwigs-Universität, Freiburg, Germany.
Bisel
Philippe
P
Weckert
Edgar
E
Frahm
August Wilhelm
AW
D000598:Amino Acids, Cyclic / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003500:Cyclization; D004952:Esters / Q000737:chemistry; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D006358:Hot Temperature; D006868:Hydrolysis; D008956:Models, Chemical; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D013464:Sulfuric Acids / Q000494:pharmacology
D000598:Amino Acids, Cyclic; D004952:Esters; D012997:Solvents; D013464:Sulfuric Acids; D018698:Glutamic Acid; C033158:sulfuric acid