Asymmetric hydrogenation of dehydrodipeptides bearing different protecting groups.

N-[(Z)-N-Benzoyl- or N-boc-(2-fluorophenyl)dehydroalanyl]-(R)- or (S)-phenyl-alanines 1,2,5 and 6 were hydrogenated in the presence of chiral and achiral rhodium complexes. The optical induction is compared to the results obtained using the corresponding esters as substrates.

Asymmetric hydrogenation of dehydrodipeptide esters bearing different protective groups.

N-[(Z)-N-Benzoyl- or N-Boc-(2-fluorophenyl)dehydroalanyl]-(R)- or (S)-phenylalanine esters were synthesized and hydrogenated to give the corresponding dipeptide derivatives with optical yields in the range of 53-87% de using the cationic rhodium complexes of PROPRAPHOS and BPPM. The efficiency of chiral diphosphine ligands as well the effect of the chiral center in the substrate on the catalytic asymmetric induction was studied.

Unusual amino acids. VIII. Asymmetric hydrogenation of some heteroaryl-N-Cbz and N-Boc aminocinnamic acid derivatives.

(Z)-alpha-[(Benzyloxy)- or (tert.-butyloxy)carbonylamino]-beta (thienyl)- or (furyl)-acrylic acids and their esters were prepared by known methods and hydrogenated to the corresponding optically active alanine derivatives with optical yields in the range of 58-93% ee using the cationic rhodium complex of "PROPRAPHOS".

Synthesis of non proteinogenic dipeptides by asymmetric hydrogenation.

N-Boc protected non-proteinogenic dipeptides with D,L- and L,L-configuration were prepared by catalytic asymmetric hydrogenation of the corresponding dehydrophenylalanyl-(L)-phenylalanine derivatives. The configuration of the new stereogenic centre depends first of all on the catalyst configuration and is less influenced by the substrate configuration. Diastereomeric excesses in the range of 80-96% de could be increased up to 99% by recrystallization. Analytical data of selected new compounds are given.

Synthesis of non-proteinogenic (D)- or (L)-amino acids by asymmetric hydrogenation.

Non-proteinogenic amino acids play an increasing role in oligopeptide chemistry. Their pharmacological and chemical properties, caused by D-configuration and "unnatural" residues, are more and more used for drug design. Different methods of asymmetric synthesis have been developed during the last decade to prepare "unusual" amino acids. One of them, the asymmetric hydrogenation of dehydroamino aids catalyzed by chiral rhodium (I) complexes, will be described. A series of examples, D- and L-configured, like naphthyl-, thienyl-, furyl-, and pyridylalanines, as well as phenylalanines substituted by chlorine, fluorine, p-nitro, p-methyl, p-trifluoromethyl, p-isopropyl, and p-tert-butyl have been prepared and characterized. Some analytical data like melting points and values of optical rotation are summarized in tables.

Unusual amino acids. I: Asymmetric synthesis of furylalanine derivatives.

Nonproteinogenic amino acids are valuable active compounds from their pharmacological and biochemical effects and also as novel building blocks for peptides. The preparation of furylalanine derivatives by asymmetric hydrogenation is described. Amino-phosphine-phosphinite-rhodium complexes catalyzed the hydrogenation of the prochiral dehydroamino acid precursors in high rate and with enantioselectivities of 70-90% ee. Substrate-catalyst ratios up to 2,000 can be used depending on the catalyst applied. The procedure turns out to be suitable for larger scale preparations.