JPH0834766A - Antitumor material be-39,907s - Google Patents

Abstract

PURPOSE:To obtain a new compound useful as an antitumor agent showing strong inhibitory effect on proliferation of human and mouse tumor cells. CONSTITUTION:This compound is shown by formula I (R is H or a lower alkyl) such as BE-39,907A1 of formula II. Properties: reddish orange solid. Molecular formula: C8H10N2O2. Solubility: readily soluble in methanol and acetone and insoluble in n-hexane: Color reaction: positive in iodine reaction and phosphomolybdic acid reaction. Distinction of acidity, neutrality and basicity: a basic substance. The compound is obtained by culturing a bacterium [preferably Saccharopolyspora sp. A39,907 (FERM P-14,071)] belonging to the genus Saccharopolyspora capable of producing a compound of formula II or formula III or its variant, collecting the compound of formula II or formula III from its culture solution and its cell and optionally alkylating, alkanoylating or benzoylating the compound of formula III.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention is useful in the field of medicine, and more specifically, it relates to a novel compound group having an antitumor activity by inhibiting the growth of tumor cells, a process for producing the same, a use thereof, and the compound. It relates to the microorganisms produced.

[0002]

2. Description of the Related Art In the field of cancer chemotherapy, clinical application of many microbial metabolites such as bleomycin and adriamycin has been attempted, and they have been practically used clinically. There is. However, the effect is not always sufficient for various kinds of tumors, and there is a constant demand for superior new antitumor substances.

[0003]

In view of the present situation as described above, the present inventors intend to find an excellent novel antitumor substance by broadly screening microbial metabolites.

[0004]

Means for Solving the Problems In order to solve the above problems, the present inventors extensively screened microbial secondary metabolites for substances having antitumor activity, and as a result, were represented by the following general formula [I]. The present invention has been completed by discovering that these compounds exhibit excellent antitumor activity.

That is, the present invention provides a novel general formula [I]

[0006]

[Chemical 7] (In the formula, R represents a hydrogen atom, a lower alkyl group, a lower alkylcarbonyl group or a benzoyl group), a method for producing the same and a use thereof, and a saccharopolis having the ability to produce the compound of the formula [I] Paula (Saccha
The present invention relates to a microorganism belonging to the genus ropolyspora).

Next, terms used in this specification will be described. The term "lower" as used herein means that the group or compound to which the term is attached has 6 or less, preferably 4 or less carbon atoms.

The "lower alkyl group" is a linear or branched alkyl group having 1 to 6 carbon atoms, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group,
A hexyl group and the like can be mentioned.

The "lower alkanoyl group" has 1 to 1 carbon atoms.
It shows 6 linear or branched alkanoyl groups, and examples thereof include formyl group, acetyl group, propanoyl group, butyryl group, isobutyryl group, pentanoyl group, isopentanoyl group, hexanoyl group and isohexanoyl group. .

The physicochemical properties of the novel antitumor substances BE-39007 related to the present invention are shown below.

Here, the compound of the formula [III] is converted into BE-3.
9907A1 and designated BE-39 as a compound of formula [II].
907A2.

The meanings of the abbreviations used in the NMR measurement are shown below. br: broad s: singlet d: doublet dd: double doublet q: quartet m: multiplet J: coupling constant Hz: Hertz The physicochemical properties of the compound of the present invention are shown below. Physicochemical properties of BE-39907A1 Properties: Red-orange solid Molecular formula: C ₈ H ₁₀ N ₂ O ₂ Structural formula:

[0013]

Embedded image Mass spectrum: High resolution EI-MS: m / z 16
6.0755 [M ⁺ ] UV and visible absorption spectrum: λ _max (MeOH, nm
(Ε)) 259 (9,060), 387 (14.0)
0), 485 (4,580) infrared absorption spectrum ν _max (KBr, cm ⁻¹ ): 33
63, 1618, 1599, 1564, 1508, 13
69,1257,1103,837 ¹ H-NMR spectrum (400MHz, CDCl _3, δ
ppm): 2.88 (3H, d, J = 5.9Hz),
4.08 (3H, s), 5.43 (1H, q, J = 5.
9Hz), 6.33 (1H, d, J = 9.8Hz),
6.50 (1H, d, J = 2.9Hz), 7.37 (1
H, dd, J = 2.9, 9.8 Hz) ¹³ C-NMR spectrum (125 MHz, CDCl ₃ ,
δppm): 29.1, 48.6, 92.0, 124.
2,126.6,143.3,144.2,180.4 Thin layer chromatography: (Kieselgel 6 manufactured by Merck & Co., Inc.
0F ₂₅₄ ) Rf value: 0.80 (developing solvent chloroform: methanol = 10: 1) Solubility: readily soluble in methanol, acetone, ethyl acetate, chloroform, insoluble in n-hexane.

Distinction between acidic, neutral and basic substances: basic substance Color reaction: iodine reaction Positive phosphomolybdic acid reaction Positive Physicochemical properties of BE-39907A2 : yellow solid Molecular formula: C ₇ H ₈ N ₂ O ₂ Structural formula:

[0015]

[Chemical 9] Mass spectrum: High resolution EI-MS: m / z 15
2.0578 [M ⁺ ] UV and visible absorption spectrum: λ _max (MeOH, nm
(Ε)) 234 (11,400), 328 (8,85)
0), 431 (3,070) infrared absorption spectrum ν _max (KBr, cm ⁻¹ ): 33
23, 1616, 1579, 1518, 1417, 13
15,993,939,8391 ¹ H-NMR spectrum (500 MHz, DMSO-
_{d 6, ppm): 2.67 (} 3H, d, J = 5.2H
z), 6.02 (1H, d, J = 2.4 Hz), 6.4
1 (1H, q, J = 5.2 Hz), 6.41 (1H,
d, J = 9.8 Hz), 7.15 (1H, dd, J =
9.8, 2.4 Hz), 12.6 (1H, brs) ¹³ C
-NMR spectrum (100MHz, DMSO-d _6,
ppm): 28.6, 86.2, 126.6, 139.
7, 143.5, 150.1, 181.9 Thin layer chromatography: (Kieselgel 6 manufactured by Merck & Co., Inc.
0F ₂₅₄ ) Rf value: 0.74 (developing solvent chloroform: methanol = 10: 1) Solubility: easily soluble in methanol and acetone, soluble in ethyl acetate and chloroform, insoluble in n-hexane.

Distinction between acidic, neutral and basic substances: amphoteric substance Color reaction: iodine reaction positive phosphomolybdic acid reaction positive Next, a method for producing BE-39907 will be described. The microorganism used in the production of the antitumor substance BE-39907 of the present invention or a mutant strain thereof is the antitumor substance BE-399.
Any one may be used as long as it produces 07A1 or BE-39907A2, and examples thereof include microorganisms having the following mycological properties.

Bacteriological Properties of A39907 Strain 1. Morphology A39907 strain is a spore (1.
3 to 1.0 × 0.7 to 0.6 μm) are connected to form long straight and curved long spore chains, and the surface of the spore sheath is hair-like. Rupture of basal hyphae is observed, but special organs such as sporangia, flagella spores, and sclerotium are not observed. 2. Culture properties in various agar plates (28 ° C 14
Day culture)

[0018]

[Table 1] 3. Growth temperature (starch / inorganic salt agar culture for 14 days) Optimal growth conditions 12 ° C: No growth 16 ° C: Growth is trace level 19 ° C: Good growth, no aerial mycelium formation 23 ° C: Very good growth, aerial mycelia Good 28 ° C: Very good growth, good formation of aerial mycelium 32 ° C: Very good growth, good formation of aerial mycelium 37 ° C: Good growth, no formation of aerial mycelium 43 ° C: No growth 4. Physiological properties (1) Gelatin liquefaction positive (glucose / peptone / gelatin medium) (2) Starch hydrolysis positive (starch / inorganic salt agar medium) (3) Skim milk powder coagulation negative (skimmed milk medium) (4) 4. Peptonization of skim milk powder positive (skim milk medium) (5) Formation of melanin-like pigment negative (6) Salt tolerance Growing at 13% or less salt content (yeast / malt agar medium) Utilization of carbon source Using Pridham Godleybe agar as a basal medium, the following sugars were added and cultured at 28 ° C for 14 days. D-glucose + raffinose + D-xylose-D-mannitol + L-arabinose-inositol + L-rhamnose + salicin ± D-fructose + sucrose + D-galactose + 6. Cell wall composition meso-diaminopimelic acid, arabinose and galactose were detected in the cell wall, and the cell wall type was I.
It is considered to be V-shaped. The whole cell sugar components characteristic of classification are arabinose and galactose, and the sugar pattern is A
It was a mold. Further, mycolic acid is not detected, the main menaquinone was MK-9 (H ₄₎ and MK-10 (H _4).

From the above mycological properties, the A39907 strain is considered to belong to the actinomycete Saccharopolispora.
Therefore, the A39907 strain was replaced with Saccharopolyspora sp. A39907 (Saccharopolyspor).
a sp. A 39907).

This strain has been deposited at the Institute of Biotechnology, Institute of Biotechnology, Ministry of International Trade and Industry, and the deposit number of the Micro Engineering Research Institute is Micro Engineering Research Institute No. 14071 (FERM P-1).
4071).

The microorganism used in the present invention may be any actinomycete that belongs to the genus Saccharopolyspora and has the ability to produce the antitumor substance BE-39907, but is preferably Saccharomyces. Polyspora SP A39907 or its mutants are mentioned. Examples of the mutant strain include irradiation treatment with X-rays or ultraviolet rays, such as nitrogen mustard, azaserine, nitrous acid, 2-aminopurine or N-methyl-N'-nitro-N-nitrosoguanidine (NTG). Examples include microorganisms obtained by mutating BE-39907s-producing bacteria by treatment with a mutagenizing agent or a commonly used bacterial species conversion treatment method such as phage contact, transformation, transduction or conjugation.

BE-39907s of the present invention are BE-3.
BE-39907s are collected from the culture broth and the bacterial cells by inoculating a nutrient source-containing medium with the 9907-producing strain A39907 strain or a mutant strain thereof and aerobically culturing, and if necessary, pharmaceutical It can be produced by using an acceptable salt.

As the nutrient source, those known as the nutrient source for actinomycetes can be used, and as the carbon source, for example, commercially available glucose, glycerin, maltose, starch, sucrose, molasses, dextrin, etc. are used alone or as a mixture. Used. As the nitrogen source, for example, commercially available soybean flour, corn gluten meal, corn steep liquor,
Meat extract, defatted meat-and-bone meal, meat meal, yeast extract, dried yeast, cottonseed flour, peptone, wheat germ, defatted rice bran, fish meal, inorganic ammonium salt, sodium nitrate and the like are used alone or as a mixture. As the inorganic salt, for example, commercially available calcium carbonate, calcium chloride, sodium chloride, sodium bromide, potassium chloride, magnesium sulfate, various phosphates and the like can be used alone or as a mixture. In addition, if necessary, trace amounts of heavy metal salts such as iron, manganese, cobalt, molybdenum, copper and zinc may be added. When foaming is remarkable, vegetable oils such as soybean oil and linseed oil, higher alcohols such as octadecanol, and various silicon compounds may be appropriately added as an antifoaming agent. In addition to these, those useful for the production of BE-39907s used by the producing bacterium can be appropriately used, and examples thereof include 3- (N-morpholino) propanesulfonic acid and sodium borate.

The culturing method can be performed in the same manner as a general microbial metabolite production method, and may be solid culture or liquid culture. In the case of liquid culture, any culture method such as static culture, stirring culture, shaking culture, aeration culture and the like may be carried out, but shaking culture or deep aeration stirring culture is particularly preferable.
The appropriate culture temperature is 19 ° C to 37 ° C, but 23 ° C to 3 ° C.
2 ° C is preferred. The culturing time is appropriately 72 hours to 288 hours, but is preferably 144 hours to 240 hours.

BE-39 of interest from culture medium and cells
To collect 907s, a separation means usually used for collecting from a culture of a metabolite produced by a microorganism is appropriately used. BE-39907s are present mainly in the filtrate, in the culture filtrate and in the microbial cells, and therefore, they are usually separated from the culture filtrate or the microbial cells by, for example, a solvent extraction method, an ion exchange resin method, an adsorption or partition chromatography method, It can be purified by performing gel filtration or the like alone or in combination. Further, high performance liquid chromatography, thin layer chromatography and the like can be appropriately used for extraction and purification.

Examples of preferable separation-purification include the following methods. First, the culture solution is filtered to obtain a filtrate. The filtrate is extracted with ethyl acetate, the extract is concentrated under reduced pressure, and then subjected to silica gel column chromatography (chloroform / methanol) to obtain crude substances of BE-39907A1 and A2. Each of them can be obtained as a pure substance by purifying the product again by silica gel column chromatography.

The compound of formula [II] (BE-39907A
2) is easily converted into a compound in which R is a lower alkyl group, a lower alkanoyl group or a benzoyl group in the general formula [I] by an alkylation, alkanoylation or benzoylation method well known in the field of organic chemistry. can do.

BE-39907A, for example in the presence of a base
2 can be treated with a lower alkylating agent to give a compound of the formula [I] in which R is a lower alkyl group.

Further, BE-39907A2 can be treated with an acid anhydride or an acid halide in the presence of a base to easily obtain the corresponding lower alkanoyl derivative or benzoyl derivative.

Next, in order to show the usefulness of the compound of the present invention, the growth inhibitory effect of the compound of the present invention on tumor cells was measured. Anti-tumor activity of BE-39907s In order to determine the growth-inhibitory effect of anti-tumor substances BE-39907s on mouse experimental tumor cells, in vitro.
The test was performed at ro. The antitumor effect test against mouse leukemia cells P388 was carried out by dissolving BE-39907s in dimethyl sulfoxide, and then adding 10% fetal bovine serum-containing RP.
Cell culture medium containing 2 × 10 ³ tumor cells (PRMI16 containing 10% fetal bovine serum) was serially diluted with MI1640 medium (containing 20 μM 2-mercaptoethanol).
50 μl was added to 50 μl of 40 medium and 20 μM of 2-mercaptoethanol. After culturing at 37 ° C. for 72 hours under 5% CO ₂ , it was compared with the control group by the MTT measurement method.

An antitumor test against mouse colon cancer cell colon26 was carried out by dissolving BE-39907s in dimethyl sulfoxide and then adding RPMI16 containing 10% fetal bovine serum.
Cell culture medium (PRMI1640 containing 10% fetal bovine serum) serially diluted with 40 medium and containing 1 × 10 ³ tumor cells.
100 μl was added to 100 μl of the medium. After culturing at 37 ° C. for 72 hours under 5% CO ₂ , the cells were fixed with 50% trichloroacetic acid and stained with 0.4% sulforhodamine B.
The dye was extracted from the cells using 10 mM Tris buffer. The absorbance at 550 nm was measured using 450 nm as a control wavelength and compared with the control group. As a result, BE-3
9907s showed strong growth inhibitory activity against both cancer cells, and the 50% growth inhibitory concentration (IC ₅₀ ) was as shown in Table 2.

Further, the antitumor activity of BE-39907s against human cancer cells was tested in vitro. The cells are human colon cancer cell DLD-1, human lung cancer cell PC-1.
3 and human gastric cancer cells MKN-45 were used, and the cell culture medium was RPM containing 10% fetal bovine serum for all the cancer cells.
I1640 medium was used. BE-39907s were first dissolved in dimethyl sulfoxide, and then serially diluted with RPMI1640 medium containing 10% fetal bovine serum to prepare a test solution. For the assay of cancer cell growth inhibition, 100 μl of a cell culture medium containing 1 × 10 ³ cancer cells was dispensed into a 96-well microplate and cultured at 37 ° C. for 24 hours under 5% CO ₂ , 100 μl of the above test solution was added. Furthermore, after culturing for 72 hours, the cells were fixed with 50% trichloroacetic acid, and
A comparison was made with the control group using the same method as for n 26 cells. As a result, BE-39907s also showed strong growth inhibitory activity in human tumor cells, and their 50% growth inhibitory concentration (IC ₅₀ ) was as shown in Table 2.

[0033]

[Table 2] As described above, BE-39907s have a remarkable growth-inhibitory effect on mouse and human cancer cells. Therefore, the present invention is useful as an antitumor agent for mammals including humans.

When the compound of the present invention is used as an antitumor agent, various dosage forms can be selected, for example, oral preparations such as tablets, capsules, powders, granules and liquids, such as solutions and suspensions. And a sterilized liquid parenteral preparation.

The solid preparation can be produced as it is in the form of tablets, capsules, granules or powders, or can be produced using appropriate additives. Examples of the additives include sugars such as lactose and glucose, starches such as corn, wheat and rice, fatty acids such as stearic acid, and inorganic salts such as sodium metasilicate, magnesium aluminate and anhydrous calcium phosphate, for example. Polyvinylpyrrolidone, synthetic polymers such as polyalkylene glycol, for example, calcium stearate, fatty acid salts such as magnesium stearate, alcohols such as stearyl alcohol, benzyl alcohol, such as methyl cellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, etc. Synthetic cellulose derivatives, others,
Water, gelatin, talc, vegetable oil, gum arabic and the like commonly used additives are included.

The solid preparations such as tablets, capsules, granules and powders can contain the active ingredient generally in an amount of 0.1 to 100% by weight, preferably 5 to 100% by weight.

The liquid preparation uses water, alcohols, or appropriate additives usually used in liquid preparations such as oil derived from plants such as soybean oil, peanut oil, sesame oil, etc., suspensions, syrups, injections. And the like.

In particular, when administered parenterally by intramuscular injection, intravenous injection or subcutaneous injection, suitable solvents include distilled water for injection, lidocaine hydrochloride aqueous solution (for intramuscular injection), physiological saline, Examples thereof include an aqueous glucose solution, ethanol, a liquid for intravenous injection (for example, an aqueous solution of citric acid, sodium citrate, etc.), an electrolyte solution (for example, intravenous drip, for intravenous injection), or a mixed solution thereof.

Further, these injections may be dissolved in advance, or may be in the form of a powder or a powder to which appropriate additives are added, which is dissolved at the time of use. These injection solutions may contain the active ingredient in an amount of usually 0.1 to 10% by weight, preferably 1 to 5% by weight.

The liquid preparation such as suspension or syrup for oral administration may contain 0.5 to 10% by weight of the active ingredient.

The actual preferable dosage of the compound of the present invention can be appropriately increased or decreased depending on the kind of the compound used, the kind of the compounded composition, the application frequency and the specific site to be treated and the medical condition of the patient. For example, the daily dose per adult is 10 to 500 mg for oral administration, and 10 to 100 mg per day for parenteral administration, preferably intravenous injection. In addition,
The frequency of administration varies depending on the administration method and symptoms, but the administration can be performed once or in 2 to 5 divided doses.

[0042]

The present invention will be described in more detail with reference to the following examples. However, the present invention is not limited to these examples, and the means for modifying the examples and the present invention are obvious. It includes all methods for producing, concentrating, extracting and purifying BE-39907s by known means based on the properties of BE-39907s thus obtained. Example 1 Actinomycete A39907 strain inoculated on a slant soft agar medium had glucose 0.2%, dextrin 2%, and meatmeal 0.
5%, defatted rice bran 0.5%, defatted meat and bone meal 0.2%, dry yeast 0.1%, magnesium sulfate 0.05%, sodium bromide 0.05%, sodium chloride 0.5%, phosphoric acid Dipotassium hydrogen 0.1%, ferrous sulfate 0.0002%, cupric chloride 0.00004%, manganese chloride 0.0000
4%, cobalt chloride 0.00004%, zinc sulfate 0.0
Inoculate four 500 ml Erlenmeyer flasks containing 100 ml of a medium (pH 7.2) consisting of 0008%, sodium borate 0.00008% and ammonium molybdate 0.00024%, and incubate at 28 ° C. for 120 hours on a rotary shaker ( The culture was performed at 180 rpm.

2 ml of this culture medium was added to 10 ml of the above medium.
Inoculate 100 Erlenmeyer flasks with a capacity of 500 ml containing 0 ml, and rotate at 28 ° C for 240 hours.
Cultured above.

The culture broth thus obtained (about 10
10 L of ethyl acetate was added to L), and the mixture was stirred at room temperature for 30 minutes. Celite was added thereto, and the cells were separated by a filtration method to obtain an ethyl acetate layer. The ethyl acetate layer was dehydrated with anhydrous sodium sulfate and then concentrated to dryness under reduced pressure. The residue was dissolved in 150 ml of chloroform and the silica gel column (10
0g, adsorbed on a Merck Kieselgel 60) column,
After washing with chloroform, chloroform / methanol (1
It was eluted with a mixed solution of 00: 1) to obtain a fraction 1 mainly containing BE-39907A1 and a fraction 2 mainly containing BE-39907A2.

Fraction 1 was concentrated, dissolved in 7 ml of chloroform, applied to a 40 g silica gel column, washed with chloroform, and then eluted with a mixed solution of chloroform / ethanol (200: 1) to give a red-orange color of BE-39907A1. 195 mg of a solid was obtained.

Fraction 2 was concentrated, dissolved in 25 ml of toluene, applied to a 40 g silica gel column, and eluted with a mixed solution of toluene / ethyl acetate (10: 1) to obtain BE.
21 mg of -39907A2 yellow solid was obtained.

The formulation examples of the compound of the present invention are shown below.
However, the formulation of the compound of the present invention is limited to this formulation example.
Not something.Formulation example 1 This substance (BE-39907A1) 10 parts Heavy magnesium oxide 15 parts Lactose 75 parts are uniformly mixed to obtain powder or fine particles of 350 μm or less.
Use as a powder. Put this powder in a capsule container
I used it as an agent.Formulation example 2 This substance (BE-39907A1) 45 parts Starch 15 parts Lactose 16 parts Crystalline cellulose 21 parts Polyvinyl alcohol 3 parts Distilled water 30 parts After uniform mixing, crush granulation and drying, followed by sieving
To obtain granules having a size of 1410 to 177 μm.Formulation example 3 After the granules were prepared in the same manner as in Formulation Example 2, the granules were prepared.
Add 4 parts calcium stearate to 96 parts agent
By compression molding, tablets with a diameter of 10 mm were produced. Formulation example 4 Binding to 90 parts of the granules obtained by the method of Formulation Example 2
Crystalline cellulose 10 parts and calcium stearate 3 parts
After adding and compression molding into tablets with a diameter of 8 mm,
Syrup gelatin, precipitated calcium carbonate mixed suspension
To prepare a sugar-coated tablet.Formulation example 5 This substance (BE-39907A1) 0.6 part Nonionic surfactant 2.4 parts Physiological saline 97 parts After heating and mixing, put in ampoule, sterilize and inject.
An agent was prepared.

[0048]

INDUSTRIAL APPLICABILITY The BE-39907s of the present invention show a growth inhibitory effect on human and mouse tumor cells, and are therefore useful as antitumor agents in the field of medicine.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location C07C 251/68 8829-4H C12N 1/20 A 8828-4B C12P 13/00 2121-4B // ( (C12N 1/20 C12R 1:01) (C12P 13/00 C12R 1:01) (72) Inventor Hiroyuki Suda 3 Okubo, Tsukuba City, Ibaraki Prefecture

Claims (11)

[Claims] 1. A compound represented by the general formula [I]: (In the formula, R represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, or a benzoyl group). 2. Saccharo
culturing a microorganism or a mutant strain thereof which belongs to the genus polyspora) and has the ability to produce the compound represented by the formula [II], and collects the compound represented by the formula [II] from the culture solution and cells. Of the formula [II]: The manufacturing method of the compound represented by. 3. Saccharo
A microorganism belonging to the genus polyspora) and having the ability to produce the compound represented by the formula [II], or a mutant strain thereof is cultured, and the culture solution and cells are used to express the compound of the formula [II] A compound of the general formula [I], characterized in that the compound of formula [II] is collected and the compound of formula [II] is alkylated, alkanoylated or benzoylated (In the formula, R represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group, or a benzoyl group). 4. A Saccharo spora (Saccharo)
culturing a microorganism belonging to the genus polyspora) and having the ability to produce the compound represented by the formula [III], or a mutant strain thereof, and collecting the compound represented by the formula [III] from the culture solution and bacterial cells. Of the formula [III]: The manufacturing method of the compound represented by. 5. A microorganism or its mutant strain is Saccharopolyspora sp. A39907 (Saccharopo).
lyspora sp. A39907).
The manufacturing method described. 6. A microorganism or its mutant strain is Saccharopolyspora sp. A39907 (Saccharopo).
lyspora sp. A39907).
The manufacturing method described. 7. A compound represented by the general formula [I]: An antitumor agent containing a compound represented by the formula (wherein R represents a hydrogen atom, a lower alkyl group, a lower alkanoyl group or a benzoyl group) as an active ingredient. 8. A Saccharopol having the ability to produce a compound of general formula [II].
a microorganism belonging to the genus Yspora) or a mutant strain thereof. 9. The microorganism is Saccharopolyspora sp. A39907 (Saccharopolyspor).
a sp. A39907), The microorganism according to claim 8 or a mutant thereof. 10. Saccharops having the ability to produce compounds of general formula [III].
A microorganism belonging to the genus Olyspora) or a mutant strain thereof. 11. A microorganism is Saccharopolyspora sp. A39907 (Saccharopolyspo).
ra sp. A39907), The microorganism or a mutant strain thereof according to claim 10.