Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of...
Patent
1997-06-10
1998-12-01
Degen, Nancy
Chemistry: molecular biology and microbiology
Micro-organism, per se ; compositions thereof; proces of...
4352541, 43525411, 514550, 514675, 514706, 514740, C12N 114, C12N 115, A61K 31095, A61K 3112
Patent
active
058437550
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel compound and a method for producing the compound. In particular, the present invention relates to a compound having an antitumor activity and produced by a mold belonging to the genus Ascochyta.
BACKGROUND ART
Many compounds have been hitherto reported as antitumor antibiotics, such as anthracyclines and mitomycins.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide a novel antitumor substance and a method for producing the substance.
The present inventors have found out a group of novel compounds produced by a mold belonging to the genus Ascochyta, and found out that the group of compounds have an antitumor activity. Thus the present invention has been completed.
The compound provided by the present invention is represented by the following structural formula: ##STR1##
The compound represented by the foregoing structural formula involves a plurality of tautomers. Of the tautomers, a first compound is designated as FE399-P1, which is capable of forming a major component of a tautomeric equilibrium mixture having the following physicochemical properties.
(1) Appearance of dry preparation: white powder.
(2) Melting point: 260.degree. to 265.degree. C. (decomposition).
(3) Solubility: readily soluble in pyridine and acetic acid, soluble in dimethyl sulfoxide, chloroform, ethyl acetate, methanol, and acetonitrile, and scarcely soluble in water.
(4) Ultraviolet absorption spectrum: end absorption appears in the vicinity of 200 nm in an acetonitrile solution.
(5) Chemical shift values (.delta., unit: ppm) obtained by .sup.1 H nuclear magnetic resonance spectrum (600 MHz, pyridine-d.sub.5):
9.55 (1H, s), 7.97 (1H, d), 5.84 (1H, t), 5.19 (1H, brs), 4.88 (1H, s), 4.04 (2H, m), 3.65 (1H, d), 3.47 (1H, d), 2.56 (1H, t), 2.37 (1H, t), 2.12 (1H, m), 1.11-1.51, 0.83 (1H, t).
(6) Chemical shift values (.delta., unit: ppm) obtained by .sup.13 C nuclear magnetic resonance spectrum (150 MHz, solvent: pyridine-d.sub.5):
176.001, 174.731, 171.733, 75.383, 55.235, 55.114, 47.820, 45.354, 36.572, 35.866, 32.780, 26.992, 26.932, 25.349, 22.492, 19.208, 14.109.
(7) Chemical shift values (.delta., unit: ppm) obtained by .sup.13 C nuclear magnetic resonance spectrum (100 MHz, solvent: DMSO-d.sub.6):
174.8, 173.1, 170.3, 74.2, 53.5, 52.6, 47.4, 44.1, 36.0, 34.9, 32.3, 26.9, 26.6, 26.6, 24.8, 21.6, 18.3, 13.7.
(8) Color reaction
color development with phosphomolybdic acid: positive;
color development with anisaldehyde: positive.
(9) The first compound is separated on thin layer chromatography under the following development condition:
adsorbent: Kieselgel 60 F254, thickness: 0.25 mm;
solvent for development: chloroform:methanol=93:7;
Rf value: about 0.32.
A second compound provided by the present invention is designated as FE399-P2. The compound is capable of forming a tautomeric equilibrium mixture together with FE399-P1. The second compound is separated on thin layer chromatography under the following development condition:
adsorbent: Kieselgel 60 F254, thickness: 0.25 mm;
solvent for development: chloroform:methanol=93:7;
Rf value: about 0.42.
A third compound provided by the present invention is designated as FE399-P3. There is high possibility that FE399-P3 is capable of forming a tautomeric equilibrium mixture together with FE399-P1 and/or FE399-P2 described above. However, there remains possibility that FE399-P3 might be a partially decomposed product of FE399-P1 or FE399-P2. The third compound is separated on thin layer chromatography under the following development condition:
adsorbent: Kieselgel 60 F254, thickness: 0.25 mm;
solvent for development: chloroform:methanol=93:7;
Rf value: about 0.54.
In another aspect of the present invention, there is provided a tautomeric equilibrium mixture comprising two or three species selected from FE399-P1, FE399-P2, and FE399-P3 described above.
In still another aspect of the present invention, there is provided a method for producing the compound or the mixture described above, comprising the step
REFERENCES:
Junji Magae et al. Antitumor and Antimetastatic Activity of an Antibiotic, Ascofuranone, and Activation Phagocytes the Journal of Antibiotics (1988), vol. 41, No. 7, pp. 959-965.
Junji Magae et al. Differentiation of Mouse and Human Myeloid Leukemia Cells Induced by Antitumor Antibiotic, Ascofuranone Agric. Biol. Chem. (1988), vol. 52, No. 12, pp. 3143-4147.
Ando Toshihiko
Fudo Ryosuke
Ikenoue Yuka
Murata Masahiro
Obayashi Yoko
Ajinomoto Co. Inc.
Degen Nancy
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