Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on March 5, 2018 | https://pubs.acs.org Publication Date: April 28, 1982 | doi: 10.1021/bk-1982-0185.ch022
Asymmetric Hydrogenation of Cyclic Dipeptides Containing α,β-Dehydroamino Acid Residues and Subsequent Preparation of Optically Pure α-Amino Acids NOBUO IZUMIYA Kyushu University, Laboratory of Biochemistry, Faculty of Science, Higashi-ku, Fukuoka 812, Japan
AM-Toxin I (I, Scheme 1) is a host specific phytotoxin. To elucidate the role of the double bond in the ∆Ala residue, we planned to prepare [L-Ala ]- or [D-Ala ]-AM-toxin I (II) by hydro genation of AM-toxin I. By way of a preliminary study we hydro genated cyclo(∆Ala-L-Leu) (III) and observed unexpectedly high asymmetric induction, affording pure cyclo(L-Ala-L-Leu) (IV). 2
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Cyclo(L-Ser-L-AA) (AA=Ala, Val, Phe or Lys(ε-Ac)) was con verted by the Photaki method (1) into the corresponding cyclo (∆Ala-L-AA) and subsequently hydrogenated with Pd black in metha nol at 25°C affording cyclo(Ala-L-AA) (2). Generally high chiral inductions defined as %L-Ala minus %D-Ala in the cyclo(Ala-L-AA) were observed, ranging from 92 to 98% with yields of 63-75%. Similarly high chiral inductions (96-99%) were observed for 0097-6156/82/0185-0272$05.00/0 © 1982 American Chemical Society
Eliel and Otsuka; Asymmetric Reactions and Processes in Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1982.
Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on March 5, 2018 | https://pubs.acs.org Publication Date: April 28, 1982 | doi: 10.1021/bk-1982-0185.ch022
IZUMIYA
Cyclic Dipeptides
273
hydrogenation of a series of cyclo(∆AA'-L-AA) (∆AA'=∆Aba, ∆val or ∆Leu) prepared from cyclo(Gly-L-AA) and appropriate aldehydes (3). Hydrogenation of ∆Phe or ∆Trp i n cyclo(∆Phe or ∆Trp-L-AA) resulted in a slightly lower asymmetric induction at 25°C (3). Hydrogenation of a series of its higher homologs (e.g. cyclo(∆Homophe-LAla)), however, afforded high induction (4). Cyclo(∆Phe-L-Ala) was hydrogenated with high chiral induction at a low temperature, 0°C (4). Optically pure α-amino acids can be prepared by this route. For example, pure cyclo(L-Aba-L-Lys(ε-Ac)) obtained from cyclo (∆Aba-L-Lys(ε-Ac)) was hydrolyzed by 6 M HCl to give pure L-Aba (L-2-aminobutanoic acid) (3). Pure L-App (L-2-amino-5-phenylpentanoic acid) was prepared from cyclo(ΔΑρρ-L-Ala) and used for the synthesis of AM-toxin II (5). H -D-Phe was prepared from cyclo(∆Phe-D-Lys(ε-Ac)) and deuterium at 0°C, and synthesis of [ H2-D-Phe ']-gramicidin S (cyclic decapeptide) for NMR investi gation i s under study. The mechanism of the chiral inductions has been discussed (2^ 4). In cyclo(AAla or ALeu-L-AA), the r i g i d and planar structure of the diketopiperazine ring and the side chain containing the double bond i s an important factor inducing high asymmetry. In cyclo(APhe or ATrp-L-AA), however, the diketopiperazine ring and the aromatic ring cannot be coplanar; a somewhat poorer stereo selectivity i n the adsorption of the diketopiperazine ring on Pd i s assumed to lower the degree of asymmetric hydrogénation. 2
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Acknowledgments The author thanks Drs. S. Lee, T. Kanmera, H. Aoyagi, and Y . Hashimoto in his laboratory for their experimental assistance.
Literature cited 1. Photaki, I. J. Am. Chem. Soc. 1963, 85, 1123. 2. Lee, S.; Kanmera, T.; Aoyagi, H.; Izumiya, N. Int. J. Pept. Protein Res. 1979, 13, 207. 3. Kanmera, T.; Lee, S.; Aoyagi, H.; Izumiya, N. Int. J. Pept. Protein Res. 1980, 16, 280. 4. Hashimoto, Y.; Aoyagi, H.; Izumiya, N. Int. J. Pept. Protein Res. in preparation. 5. Shimohigashi, Y.; Izumiya, N. Int. J. Pept. Protein Res. 1978, 12, 7. RECEIVED December 14, 1981.
Eliel and Otsuka; Asymmetric Reactions and Processes in Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1982.
