Total synthesis of WS9326A, a potent tachykinin antagonist from Streptomyces violaceoniger

Chemical and Pharmaceutical Bulletin

Volumn 45, Issue 2, 1997, Pages 236-242

  Shigematsu, Nobuharu ^a   Kayakiri, Natsuko ^a   Okada, Satoshi ^a   Tanaka, Hirokazu ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

cyclic peptide lactone; photochemical isomerization; tachykinin antagonist

Indexed keywords

TACHYKININ RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG; WS 9326A;

ARTICLE; DRUG POTENCY; DRUG SYNTHESIS; ISOMERISM; PHOTOCHEMISTRY; RECEPTOR BLOCKING; STREPTOMYCES; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

EID: 0030891953     PISSN: 00092363     EISSN: None     Source Type: Journal    
DOI: 10.1248/cpb.45.236     Document Type: Article

References (18)

1. All amino acids are the L enantiomer unless otherwise noted. Standard abbreviations for amino acids, protecting groups and peptides are used [Eur. J. Biochem., 138, 9-37 (1984)]. Other abbreviations include: Boc = tert-butyloxycarbonyl, Bzl = benzyl, DMF = N,N-dimethylformamide, EDC = 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, HOBt = 1-hydroxybenzotriazole, HONSu = N-hydroxysuccinimide, RP-HPLC = reverse-phase high-performance liquid chromatography, Tce = 2,2,2-trichloroethyl, TFA = trifluoroacetic acid, TEA = triethylamine.
2. a) Hayashi K., Hashimoto M., Shigematsu N., Nishikawa M., Ezaki M., Yamashita M., Kiyoto S., Okuhara M., Kohsaka M., Imanaka H., J. Antibiot., 45, 1055-1063 (1992);
3. b) Hashimoto M., Hayashi K., Murai M., Fujii T., Nishikawa M., Kiyoto S., Okuhara M., Kohsaka M., Imanaka H., ibid., 45, 1064-1070 (1992).
4. Shigematsu N., Hayashi K., Kayakiri N., Takase S., Hashimoto M., Tanaka H., J. Org. Chem., 58, 170-175 (1993).
5. a) Schmidt U., Lieberknecht A., Wild J., Synthesis, 1988, 159-172;
6. b) Gross E., Meienhofer J. (ed.), "The Peptides," Vol. 5, Academic Press, New York, 1983, pp. 285-339.
7. van Heerden F. R., van Zyl J. J., Rall G. J. H., Brandt E. V., Roux D. G., Tetrahedron Lett., 1978, 661-662.
8. Zervas L., Borovas D., Gazis E., J. Am. Chem. Soc., 85, 3660-3666 (1963).
9. Futagawa S., Inui T., Shiba T., Bull. Chem. Soc. Jpn., 46, 3308-3310 (1973).
10. Belleau D., Malek G., J. Am. Chem. Soc., 90, 1651-1652 (1968).
11. Shimohigashi Y., Stammer C. H., Int. J. Pept. Protein Res., 20, 199-206 (1982).
12. Bregman J., Osaki K., Schmidt G. M. J., Sonntag F. I., J. Chem. Soc., 1964, 2021.
13. Corey E. J., Venkateswarlu A., J. Am. Chem. Soc., 94, 6190-6191 (1972).
14. H-Leu-D-Phe-OTce hydrochloride was prepared from Boc-Leu-OH and H-D-Phe-OTce using EDC, followed by deprotection of the Boc group with HCl/EtOAc (see Experimental section).
15. Nitz T. J., Holt E. M., Stammer C. H., J. Org. Chem., 46, 2667-2671 (1981).
16. The ΔMeTyr unit of 13 showed NOE between N-methyl protons at δ 3.17 and aromatic protons at δ 7.38 (2′,6′), indicating that ΔMeTyr has the Z configuration as shown. On the other hand, 14 showed NOE between N-methyl protons at δ 3.14 and the β-olefin proton at δ 6.63, indicating that ΔMeTyr has the E configuration as shown.
17. Forbes W. F., "In Steric Effects in Conjugated Systems," ed. by Gray G. W., Butterworths, London, 1958, p. 62.
18. Shimohigashi Y., Lee S., Aoyagi H., Kato T., Izumiya N., Int. J. Pept. Protein Res., 10, 323-327 (1977).