Relative and absolute configuration of antitumor agent SW-163D.
Our interest on engineering non-ribosomal synthetase responsible for SW-163 biosynthesis prompted us to determine the relative and absolute configuration of antitumor cyclic depsipeptide SW-163s. We first isolated and identified SW-163 homologs D, F and G as known compounds UK-63598, UK-65662 and UK-63052, respectively. Both enantiomers of the unusual constitutive amino acid, N-methylnorcoromic acid, were synthesized in chiral forms starting from (R)- and (S)-1,2-propanediol. The hydrolyzate of SW-163D, a major constituent of this family, was converted with Marfey's reagent, 1-fluoro-2,4-dinitrophenyl-5-L-alanine-amide (L-FDAA), and the resulting mixture of amino acid derivatives was subjected to an LC/MS analysis. Compared with authentic samples, the analytical data unambiguously show that SW-163D consisted of L-Ala, D-Ser and (1S, 2S)-N-methylnorcoronamic acid. The remaining stereochemistry of the N-methylcysteine moieties was determined from NOE data.
Nakaya
Mino
M
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo, Japan.
Oguri
Hiroki
H
Takahashi
Kosaku
K
Fukushi
Eri
E
Watanabe
Kenji
K
Oikawa
Hideaki
H
D000470:Alkaloids / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes / Q000737:chemistry; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D004448:Echinomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D007930:Leucine / Q000031:analogs & derivatives / Q000737:chemistry; D013058:Mass Spectrometry; D008968:Molecular Conformation; D009574:Nitro Compounds / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D011807:Quinolizines / Q000737:chemistry; D013237:Stereoisomerism; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D000596:Amino Acids; D000970:Antineoplastic Agents; D003521:Cyclopropanes; D047630:Depsipeptides; D004448:Echinomycin; D007930:Leucine; D009574:Nitro Compounds; D019946:Propylene Glycol; D011807:Quinolizines; C439871:1-fluoro-2,4-dinitrophenyl-5-leucinamide; C527822:N-methylnorcoronamic acid; C059030:UK 63052; C059306:UK 63598; C059307:UK 65662; C034245:N-methylcytisine; D000093843:Quinolizidine Alkaloids