Structure elucidation of Sch 20562, a glucosidic cyclic dehydropeptide lactone: The major component of W-10 antifungal antibiotic

Journal of Antibiotics

Volumn 52, Issue 4, 1999, Pages 383-397

  Afonso, Adriano ^a   Hon, Frank ^a   Brambilla, Ray ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; ANTIBIOTIC AGENT; ANTIFUNGAL AGENT; LACTONE DERIVATIVE; SCH 20561; SCH 20562; UNCLASSIFIED DRUG;

AEROMONAS; AMINO TERMINAL SEQUENCE; ANTIFUNGAL ACTIVITY; ARTICLE; CHEMICAL STRUCTURE; DEGRADATION; HYDROLYSIS; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; STEREOCHEMISTRY;

AEROMONAS;

EID: 0032938981     PISSN: 00218820     EISSN: None     Source Type: Journal    
DOI: 10.7164/antibiotics.52.383     Document Type: Article

References (19)

1. TAPLIN, D.; M. J. WEINSTEIN, R. T. TESTA, J. A. MARQUEZ & M. G. PATEL (Schering Corp.): Antibiotic W-10 complex, Antibiotic 20561 and Antibiotic 20562 as Antifungal Agents. U. S. Pat. 4,232,006, November 4, 1980
2. AFONSO, A.; F. HON & R. BRAMBILLA: Structure elucidation of Sch 20561, cyclic dehydropeptide lactone - a major component of W-10 antifungal antibiotic. J. Antibiotics 52: 398-406, 1999
3. Abbreviations: Aca = α-aminocrotonic acid; Asp = Aspartic acid; Asn = Asparagine; Gln = glutamine; Glu = glutamic acid; Gly = glycine; His = histidine; Hma = β-hydroxymyristic acid; Thr = threonine; Tyr = Tyrosine
4. MORRISON, D. C.: Characterization of a-keto acids as quinoxalinols. J. Am. Chem. Soc. 76: 4483-4484, 1954
5. The single Tyr unit in 1 would account for an ε value = 10,000 at 240 nm which indicated that other chromophores like 9 contribute to the high observed value for this absorption
6. IKAWA, M.; J. B. KOEPFLI, S. G. MUDD & C. NIEMANN: An agent from E. coli causing hemorrhage. The component fatty acids of the phospholipid moiety. J. Am. Chem. Soc. 75: 1035-1038, 1953
7. (a) THOMAS, D. W.; B. C. DAS, S. D. GERO & E. LEDERER: Mass spectrometry of permethylated peptide derivatives. Bioch. Biophys. Res. Commun. 32: 519-525, 1968.
8. (b) VILKAS, E. & E. LEDERER: N-Methylation de peptides par la methode de hakamori. Tetrahedron Lett. 26: 3089-3092, 1968.
9. (c) WILLIAMS, D. H.: Structural and sequencing studies on peptides by mass spectrometry. Pure & Appl. Chem. 50: 219-229, 1978
10. An analogous ozonolysis of an N-α-pentenoic beta-lactam has been reported for the deprotection of the N-functionality. COOPER, R. D. G. & F. L. JOSE: Structural studies on penicillin derivatives. J. Am. Chem. Soc. 94: 1021-1022, 1972
11. A control experiment showed that ozonolysis of N-Ac-L-His followed by a) methanolysis and permethylation afforded permethylated N-Ac-Asn (m/e 230) or, b) hydrolysis with 6 N HCl, afforded aspartic acid
12. Additionally, it was determined later in these studies that the glucosyl-N-Me-Thr unit in the peptide is prone to β-elimination to form 2 under acid hydrolysis conditions (see Scheme 6)
13. 2 to the dehydropeptide were also identified
14. The N-terminal methyloxalyl group of 15 and the nitrogen of the amide group of 4c are derived from an Aca unit linking these two fragments, and the same functionalities in fragments 16 and 15 are in turn derived from the other Aca unit linking these latter fragments
15. BODANSKY, M.; G. G. MARCONI & G. C. COLMAN: On the N-methyl-L-threonine residue in stendomycin. J. Antibiotics 21: 668-670, 1968
16. For pertinent references see: SRINIVASAN, A.; R. W. STEPHENSON & R. K. OLSEN: Conversion of threonine derivatives to dehydroaminoamino acids by elimination of β-chloro and β-tosyl derivatives. J. Org. Chem. 42: 2256-2260, 1977
17. DAVIDSON, E. A.: In Carbohydrate Chemistry, pp. 37-40, Holt, Rinehart and Winston, Inc., New York, 1967
18. BODANSKY, M.; I. IZDEBSKI & I. MURAMATSU: The Structure of the peptide antibiotic stendomycin. J. Am. Chem. Soc. 91: 2351-2358, 1969
19. AYDIN, M.; N. LUCHT, W. A. KONIG, R. LUPP, G. JUNG & G. WINKELMANN: Structure elucidation of peptide antibiotics herbicolins A and B. Liebigs Ann. Chem.: 2285-2300, 1985