111(P65) 抗真菌性シクロデプシペプチドW493 A及びBの構造決定(ポスター発表の部)

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We reported here that the structures including absolute stereochemistry of W493 A (1) and B (2) were elucidated by a combination of spectral analysis and enantioselective synthesis of 3-hydroxy-4-methyltetradecanoic acid (3). In the course of a screening for antifungal substances by the bioassay observing hyphal swelling of C. Miyabeanus, 1 and 2 were isolated from the culture broth of Fusarium sp. by CHCl_3 extraction and various chromatographies. The molecular formula of 1 and 2 were determined as C_<45>H_<74>O_<11>N_7 and C_<44>H_<72>O_<11>N_7, respectively from HRFAB-MS. The IR, ^1H, and ^<13>C NMR spectra were suggested the presence of a peptide structure, and their planar structures containing 3 as a component were determined by amino acid analysis and DQFCOSY, HMQC, HMBC experiments. Consequently, the structure of 2 was identified to be a cycloheptadepsipeptide, cyclo(3-D-allo-Thr-L-Ala-D-Ala-L-Gln-D-Tyr-L-Ile). W493 A was identified with the structure of 1 that was replaced the isoluesine residue in 2 with valine (Fig. 1). The NMR assignments for 1 and 2 were shown in Table 1 and 2. The absolute configuration of each amino acid residue was determined by chiral HPLC. The sequence of the two succesive alanines was determined on the analysis of a partial acid hydrolysate of 2 by LC-ESI-MS and chiral HPLC (Fig. 2, 3). To obtain four isomers of 3, we employed Sharpless asymmetric epoxidation. Tridec-2-yn-1-ol (6), which was prepared from 4 and 5, was converted to the epoxy alcohol 8 through partial hydrogenation and asymmetric epoxidation, 8 was successively submitted to epoxy cleavage with Me_3Al, tosylation, substitution of cyanide ion, and hydrolysis of the nitrile to give 3a. On the other hand, for inversion of the C-3 configuration, 1,2-diol 9 was converted to epoxide 13 through a three-step reaction sequence. The epoxide 13 was successively submitted to epoxy cleavage of cyanide ion and hydrolysis of the nitrile to give 3b (Scheme 1). According to essentialy the same procedure, 3c and 3d were synthesized from the enantiomer of 8. The five HMTAs (3) from hydrolysis of 2 and synthesis were derivatized to Mosher esters using 2NMA, and their NMR spectra were compaired one another. Since the spectra of the natural and 3b were identical, the absolute configuration of HMTA in 2 was determined to be 3S and 4R. The structures of 1 and 2 were reported only in 1985 as the components of the mixture, and also the stereochemistry of 3 containing in these compounds had not determined yet. These results led to the conclusion that we determined the total structure of 2, containing (3S,4R)-3-hydroxy-4-methyltetradecanoic acid (3b), which was shown in Fig. 1.
天然有機化合物討論会の論文
1997-07-20

111(P65) 抗真菌性シクロデプシペプチドW493 A及びBの構造決定(ポスター発表の部)

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