JPS6032793A - Novel bruceolide derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula I (R1 is H, t-butyldimethylsilyl, methoxyethoxymethyl, or methoxymethyl; R2 is beta-methyl-alpha,beta-unsaturated fatty acid residue having 5-18C main chain, or 1-18C straight-chain alkylcarbamic acid residue). EXAMPLE:3-o-t-Butyldimethylsilyl-15-o-3'-methyl-2'-octenoyl bruceolide. USE:A carcinostatic agent. Having low toxicity. PREPARATION:For example, a hydroxyl group at 15-position of a bruceolide derivative shown by the formula II (R3 is t-butylmethylsilyl, methoxyethoxymethyl, or methoxymethyl) is esterified with a beta-methyl-alpha,beta-unsaturated fatty acid having 5-18C main chain, or 1-18C straight-chain alkyl isocyanate is added to the derivative, to give a compound shown by the formula I (with the proviso that group R1 is R3).

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel Solce II derivative having anticancer activity represented by the following formula (1) and a method for producing the same.

H (in the formula, R4 is a hydrogen atom, a t-butyldimethylsilyl group,
methoxyethoxymethyl group or methoxymethyl group, R2 is β-methyl-α having 5 to 18 carbon atoms in the main chain,
(represents a β-unsaturated fatty acid residue or a straight-chain alkylcarbamate residue having 1 to 18 carbon atoms) [Prior art] Various natural products and compounds derived from natural products that have antitumor effects have attracted attention. A small number of these have already been used as anticancer drugs, but when applied as anticancer agents, they all have advantages and disadvantages in terms of efficacy, toxicity, etc., and the only ones that can be said to be satisfactory are (5) The current situation is that there are many.

As a natural product that has these antitumor effects, Bruc*a antldysenterlcm M, a plant of the bifaceae family that has long been used in the treatment of cancer in Ethiopia.
The active ingredient of ill is bruceantin.
It was confirmed that n) was a compound of the following formula (to).

(Kupchan et al., J, Org, Ch@m, ,
38.178 (1973); U.S. Patent No. 39693
No. 69, British Patent No. 1440094) With this confirmation, lupulce anthaline (
Bruo@antarin), Prusei 7 B (B
rua@1ss 11) l dihydropurceantin.

Purcein D, flucein E, purseoside A (Br
ua・oaId・mu) etc. or those 1111
The derived turtheolide-based compounds have been clarified and their anticancer effects have been tested (in addition to the above, (6) Doshisha Usui, 648 (1975): Doshishi Usui, 1138 (1)
981): J, Pharm, Se1.68.883 (
1979)).

However, even though these pruseolide-based compounds have an antitumor cancer effect, their toxicity and efficacy are limited.
Its use as an anticancer agent has not yet been sufficient.

[Purpose of the invention]

The purpose of the present invention is to obtain a pruseolide compound that has excellent antitumor activity and low toxicity and can be used as an anticancer agent. Tsurusato A/ (Br
usatol + formula II * J, Org.

Ch@m, 33.429 (1963)), and as a result of conducting research to create a more effective anticancer substance, chemically removing the 15-position ester group on the side of the above compound) The resulting solceolide derivative has 5 to 5 carbon atoms in its main chain.
The following formula (1) (in the formula R4 is a hydrogen atom, t-notyldimethylsilyl group,
Indicates a methoxyethoxymethyl group or a methoxymethyl group, R2txj β-methyl-α, β-unsaturated fatty acid residue having 5 to 18 carbon atoms in the main chain, or [1 to 18 carbon atoms]
It has been found that a novel compound represented by the formula (1-chain alkylcarpanic acid residue) has excellent antitumor efficacy and low toxicity, and is a useful compound as an anticancer agent.

[Structure of the invention]

The present invention is based on the general formula (wherein 8. is a hydrogen atom, a t-butyldimethylsilyl group,
Represents a methoxyethoxymethyl group or a methoxymethyl group, R2 is β-methyl-α having 5 to 18 carbon atoms in the main chain,
A new pruseolide derivative represented by (2) general formula (in the formula, R51t t-tutyldimethylsilyl group, Indicates a methoxyethoxymethyl group or a methoxymethyl group.)
The hydroxyl group at position 015 of the second id trout conductor represented by the formula is esterified with β-methy(9)-rue α,β-unsaturated fatty acid having 5 to 18 carbon atoms in the main chain, or the hydroxyl group at position 015 is esterified with α,β-unsaturated fatty acid having 1 to 18 carbon atoms in the main chain. The addition of straight-chain alkyl isocyanates results in the general formula (Iy (in the formula, R3 has the same meaning as above, and R2 is β having 5 to 18 carbon atoms in the main chain). -Methyl-α, β-unsaturated fatty acid residue or linear alkyl carpanine # residue having 1 to 18 carbon atoms.)
A method for producing a pruseolide derivative incorporated in And by hydrolyzing the compound -CIY obtained as above, the following general formula (IP (10) (wherein R2 is β-methyl-
Indicates an α,β-unsaturated fatty acid residue or a linear alkylcarbamate residue having 1 to 18 carbon atoms. ) is a method for producing a novel turtheolide derivative characterized by converting it into a trihydroxy compound represented by

The Tulse secondary derivative represented by the above general formula (1) of the present invention includes the following compounds.

3-o-t-butyldimethylsilyl-15-0-3'-
Methyl-2'-pe7thenoylpurseolide 3-o-t-gutyltsmethylsilyl-15-0-3'-
Methyl-27-hexemylgluceolide 3-o-t-butyldimethylsilyl-15-o-3'-
Methyl-2'-octenoylpurseolide 3-o-t-butyldimethylsilyl-15-o-3'-
Methyl-2'-unrsenoylpurseolide 3-o-t-butyldimethylsilyl-15-o-3'-
Methyl-2'-tetradecenoylpurseolide 3-o-t-butyldimethylsilyl-15-on-butylcarpamoylpurseolide 15-o-3'-methyl-2muoctenoylpurseolide 15 -o-3'-methyl-2'-pentenoylpurce 2nd ide 15-o-3'-methyl-2'-F'senoyl! Luceolide 1B-o-3'-Methyl-21-octadecenoylpurceolide 15-o-methylcarpamoylpurseolide 15-o-butylcarpemoylpurseolide 15-o-octylcarbamoyl! Luceolide 15-o-dodecylcarpamoyl puruseolide 1
5-o-octadecylcarpamoylpurce 2nd and above compounds of the present invention can be produced according to the following reaction formula.

(I) (II/) (B) (1)' (IF (wherein, R21R3 has the same meaning as defined above) (13) That is, for example, Brucem 9van
Pulsatol ([u
) is etherified in a conventional manner with an etherifying agent such as t-butylzomethylsilyl chloride, chloromethylmethoxyethyl ether (MwMct) or chloromethylmethyl ether (MOMCl) to give the compound (conversion).

Here, the compound axis is selected from β-methyl-α, β-unsaturated fatty acid having 5 to 18 carbon atoms in the main chain or carbon number This is to introduce 1 to 18 linear alkyl isocyanates. Compound (conversion) 1 (when solvolyzed using 1N potassium methoxide/methanol drops, the 15th position, Senesi No. 111)
Eight groups are eliminated to obtain the following compound ω). This compound Ql) is then treated with acid chlorides, acid anhydrides and alkali metal carbonates such as potassium carbonate of β-methyl-α, β-unsaturated fatty acids having 5 to 18 carbon atoms in the desired main chain. When diacylated or (14) or when a linear alkyl isocyanate having 1 to 18 carbon atoms is added to compound Q[) with triethylamine,
A compound (I)' is obtained in which an acyl group or a carbamic acid residue is introduced into the hydroxyl group at position 15. Finally, this compound (1
)'ffiWhen treated with a fluorine-containing compound such as hydrofluoric acid or tetra-n-butylammonium fluoride, a corresponding compound (■f) with a free hydroxyl group at the 3-position is obtained.

Among the above compounds, the substituent R2 in compounds (■)' and (I)' is β-
Methyl-α, β-unsaturated fatty acid residue or carbon number 1-18
This refers to straight-chain alkylcarbamate residues, including, for example, 3-methyl-2-pentenoic acid residues, 3-methyl-2-hexenoic acid residues, 3-methyl-2-hexenoic acid residues, and 3-methyl-2-hexenoic acid residues.
-to! thenic acid residue, 3-methyl-2-octenoic acid residue,
3-methyl-2-nonenoic acid residue, 3-methyl-2-7"
Heptanoic acid residue, 3-methyl-2-undecenoic acid residue, 3-
Methyl-2-tridecene acid residue, 3-methyl-2-nato-2-decenoic acid residue, 3-methyl-2-pentadecenertR
Residue, 3-methyl-2-hexadecenoic acid residue, to 3-methyl-2-! Tadecenoic acid residue, 3-methyl-2-octadecenoic acid residue, methylcarbanic acid residue, ethylcarbamic acid residue, n-globilcarbamic acid residue, n-butylcarbamic acid residue, n-pentyl carbamate residue,
n-hexylcarbamate residue, n-hegetylcarbamate residue, n-octylcarbamate residue, n-nonylcal/(minic acid residue, n-decylcarbamate residue, n
-undecylcarbamic acid) W< group, n-dodecylcarbamic acid residue, n-tridecylcarbamic acid residue 8% n
-Tetradecylcarbamate residue, n-pentadecylcarbamate residue, n-hexadecylcarbamate residue, n-to! There are tadecylcarbamate residues, n-octadecylcarbamate residues, etc.

〔Example〕

Example 1゜3-o-t-butyldimethylsilyl-15-o-3'-
Production of methyl-2'-octenoylgluceolide 3-ot-zotyldimethylsilylpurce 2nd id 55
Dissolve 0ki in 50aj of methylene chloride, add 1 of potassium carbonate.
．． 37# and 0.87 g of 3-methyl-2-oftenoyl chloride were added, and the mixture was stirred at room temperature overnight. After water and ether were added to the reaction solution to stop the reaction, the organic layer was purified with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was completely distilled off under reduced pressure, and the resulting residue was purified with silica gel (Kieselgel 60 (23) manufactured by Merck & Co., Ltd.
0-400mesh) ) 290a+Jk packed and adsorbed on 9 columns, then hexane:ethyl acetate ±1:1
The mixture was eluted under nitrogen gas pressure and evaporated under reduced pressure to obtain 240M9 (yield 35%) of the title compound as a colorless powder.

Properties Colorless powder [α)2D'+28.0° (C-025, chloroform) IHz4) Le (KBrt cm-'): 1
750, 1680, 1650.1620 Uv spectrum (λ win 3-'', nm): 270 (h6, 4oo) 22
1 (g -19,500) Mass spectrum (m/z): 577.537,49
5,477.449,207,139'H-NMRX pPm) #(CDCA5.a pPm): 0.15 (3H,
l) t O, 19 (3H.

(17) s)', 0f19 (3H, t), 0.96 (9H, s)
, 1.20-1.60 (6H, in).

1.40 (3H, s), 1.85 (3H, d, J-2H
z), 2.17 (3H, d, J-IHz) + 2.
90 (16Hy to IH+ d + ) 13.14
(I H-d, J=12Hz) 3.87 (3H, s
), 3.87.4.73 (each I H, d, J=8H
z) + 4.18 (2H.

br 8 ), 4.77 (IH, br 8 ), 5.
60 (IH, br 8 ), 6.24 (IH.

d, J=12Hz) Elemental analysis C (chi) H (chi) Actual value 62.30 7.79 Calculated value 62.58 7.88 (as molecular formula C!54H54011”) Example 2
゜Production of 3-o-t-dityldimethylsilyl-15-O-butylcarpamoylgluceolide 10 iJ of benzene, 3-o-t-butyldimethylsilylbruceolide 200119, n-butyl isocyaner) 800++v, 1. 4-diazobicyclo [2゜2
．． 2] 200 kg of octane (DABCO) was dissolved and stirred at room temperature for 2 hours. After adding methanol and stirring for 1.5 hours, the mixture was made weakly acidic with 2N hydrochloric acid, and the methanol gold was distilled off under reduced pressure. Then water was added and extracted three times with methylene chloride. The methylene chloride/part was washed twice with saturated brine and dried over anhydrous magnesium sulfate. The obtained residue was immersed in silica gel (Kieselgel 60) manufactured by Merck & Co., Ltd.
After adsorbing on a column packed with 230-400 mesh, ), 1105jlj, hexane:ethyl acetate=1=
A mixed solution of 1 is eluted under pressure of nitrogen gas, and the solvent is distilled off under reduced pressure to obtain the title compound 47WIf (yield 20%) as a colorless powder.

Properties: colorless powder 27.

[α]. , +21.1" (C=0.18, chloroform) IR spectrum (KBr, m-'): 1730
e1660s1640 ethanol UV, X vector (λ, nm): 271 (1-72
00) m&X mass spectrum 0〆z): 594,550,495*2
07'H-NMR spectrum (coct, , δppm
): 0.15, 0.17 (3H each.

@) 0.93 (3H, t), 0.96 (9H, s), 1
．． 20-1.60 (4H1m).

1.39 (3H, +s), 1.84 (3H, d, J=2
Hx), 2.90 (IH, d.

J-16Hz), 3.04-3.30 (3H, m
), 3.79, 4.70 (each IH.

d, J-8H $), 3.81 (3H, I), 4.20 (
2HIbrS), 4.76(2H,brs), 6.0
7 (IH, d, J-13Hz) Elemental analysis CC'lb) H (chi) N (chi) Actual value 58.79 7.63 2.37 Calculated value 58
．． 96 7.58 2.15 (Molecular formula C,2H4,0
1,N81) Example 3゜15-o-3'methyl-27-octenoyl! Production of luceolide 3-o-4-butyldimethylsilyl-15-o-3'-
Methyl-2'-octenoylpurce 2nd ide 119Il
v't'' Tetrahydrofuran was dissolved in 0.51 fflj, and 0.51 aJ (3 equivalents) of a tetrahydro7 run IM solution of tetra n-butylammonium fluoride was added dropwise under water cooling. After stirring for 30 minutes under water cooling, water was added to the reaction solution.

Ether was added and ether extraction was performed three times.

The organic layer was washed with saturated brine and dried over magnesium sulfate. The resulting residual Wkt silica l'k manufactured by Merck & Co.
[Kieselgel 60 (230-400 Messi,
)] After adsorption on a column packed with 47aJi and fC, it was eluted with a mixture of hexane and ethyl acetate; (yield: 62 cm).

Properties: Colorless powder (α)%8: +42. xO<C=0.09, chloroform)! R spectrum (KBr, cm): 3
500.2940, 1740, 1640 UVX vector (λ1 tano”, nm): 2'17 (gz6,00
0) ax 221 (16,000) Mass spectrum (Immediate 'z): 576 (M'), 562
．． 558,556°438, 297, 201, 1
391H-NMR spectrum (CDCA, δ, yo):
0.88 (3H, t).

1.20-1.60 (6H, m), 1.40 (3H, a
), 1.88 (3H, d.

J=2Hz), 2.16 (3H, d, J-IHs), 2
．． 36, 2.97 (each IH.

d, J-16Hz), 2.94 (IH, m), 3.12
(IH, d, J-13Hz) 3.77 (3H, m)
, 3.80, 4.70 (1 each) 1. d, J-8H
z), 4.18 (2H, brs), 4.75 (IH, b
rs), 5.58 (IH, brs).

6.26 (IH, d, J=13Hz) High-resolution mass spectrum actual measurement value: 576.2583. Calculated value: 376.2571
(As nine-dashi molecular formula C5°H40011) (21) Example 4 Production of 15-o-ffk carpamoylpurtheolide 3
-o-4-butyldimethylsilyl-15-o-notylcarpamoyl! Luceolide 100Wt acetonitrile
Dissolve 2mlK of 47% hydrofluoric acid mixture (10:1),
The mixture was stirred at room temperature for 5 hours. Next, water was added to the reaction solution and extracted with ether, and the ether layer was washed with saturated brine and dried over magnesium sulfate. The resulting residue was purified by preparative thin layer chromatography on silica gel manufactured by Merck Co., Ltd. to obtain the title compound 65N (yield 79%).

Properties: Colorless powder [α)'%': +36.80 (Ce=0.111 chloroform) IR spectrum (KBr, cm-'): 3
480,2960,1730°1660.1640 UVX vector (λ9 no”*nm): 277 (g-
4,700) ax mass spectrum (immediate 'g): 538 (M''+1), 49
4,439,392°297.201 1H-Gauss vector (CDCl2.δ,,,): 0.
92(3)1. t) 11.20-1.60 (4B, m)
, 1.40 (3H, s), 1.83 (3H, d.

(22) J=2Hz), 2.36, 2.96 (each IH
, d, J-16Hz), 3.14 (IH, d, J = 1
3Hz), 3.15 (2H, m), 3.78.4.69
(each IH, d, J-8Hz), 3.81 (3H, s),
4.20 (2H, br8).

4.75 (2H, brS), 6.08 (IH, d, J=
13Hz) Elemental analysis C (%) H (%) NC%) Actual value 58.20 6.45 2.79 Calculated value 58
．． 09 6.56 2.61 (Molecular formula C26H3507
, N) 3-o- which is the raw material for the compound (1) of the present invention
t-Butyldimethylsilylgluceolide can be obtained from known purusatol in the following manner.

Reference Example 1 Production of 3-o-t-butyldimethylsilylpurusatol Purusatol 16#t”dimethylformamide 401
Dissolve tertiary dithyldimethylsilyl chloride in 15.
76F and 15.76 g of imidazole were added and stirred overnight at room temperature. Approximately 2J of water was added to the reaction solution to stop the reaction, and the mixture was extracted four times with ether. The ether layer was washed once with water and then twice with saturated brine, and then dried over anhydrous magnesium sulfate.

Kiesel 60 (manufactured by Merck & Co., Ltd., 70-230 mesh) 15 in which the above ether extract was suspended in chloroform.
It was loaded onto a 5-diameter column packed with 0.9'i and eluted using a chloroform/methanol (20:l) mixture. Crude 3-o-t-butylnomethylsilylpurzatol was extracted from the eluate by approx. 20 II was obtained. When this crude product was recrystallized from benzene, 16.62% of colorless needle crystals were obtained (yield: 85%).
h) was obtained.

Properties: Colorless needle crystals Melting point: 190-192°C [α] 2 total + 18.80 (C-0,171 chloroform) IR spectrum (KBr, m): 1740,16
80.1620 ethanol try spectrum (λ, nm): 21B (ε-27,
000) lLX 269 (g=13,400) Elemental analysis' C (%) H (%) Actual value 60.52 7.49 Calculated value 60.54 7.30 (Molecular formula C5□H4,0,, as Si) Reference Example 2 Production of 3-o-t-butyldimethylsilylpurseolide 3-o-t-butyldimethylsilylbrusatol 4,
It was added to 99d of potassium methoxide/methanol solution of 9419'klN, and stirred at room temperature for about 30 minutes. Neutralize using a methanol solution of hydrochloric acid, and remove the precipitated potassium chloride from p
After separation, methanol was distilled off under reduced pressure. The residue was suspended in ethyl acetate using Kieserglu 60 (manufactured by Merck & Co., Ltd., 7
Loaded onto a column with a diameter of 3 (1) packed with 0-230 mesh, ) 1001 and eluted with ethyl acetate, the desired 3-
o-t-butyldimethylsilylpurtheolide 3.69
Ii was obtained. (Yield: 86%) Properties: Colorless needle crystals Melting point: 168-170°C [α] 2 degrees + 30.0 degrees (C depth 0.15.Chloroform) IR spectrum (IGlr, cm-'): 1720.
1670.1610UV, c vector (λ:, −“l
nm ): 270 ('-I JO00) Elemental analysis: (25) C (chi) H (chi) Actual value 58.41 7.46 Calculated value 58.67 7.30 (as molecular formula C27H4001O") [Effect of the invention ] The compound of the present invention has a strong antitumor activity against murine leukemia P388, which is almost as strong as that of the known compound brusatol (T) or purceantin bacteria.Furthermore, its toxicity is lower than that of brusatol or purceantin. Future development is expected as a new anti-tumor drug.The toxicity and survival rate (IL8S>) of representative compounds belonging to compound (1) are listed below in Table 1.

(26) Procedural amendment (spontaneous) Date G/2F 1, 1988, Case description 1988 Patent Application No. 1 IfO2σFg λ Name of the invention Novel pruseolide derivatives and their manufacturing method 3, Person making the amendment Relationship with the case Patent Applicant Address: 2-1-40 Dojimahama, Kita-ku, Osaka Name (19
0) Suntory Limited Representative: Keizo Saharu 44, Agent address: Suntory Limited Patent Office, 1-2-3 Motoakasaka, Minato-ku, Tokyo (telephone: 470-1131) 5. Date of amendment order: None 6. Due to amendment Increased number of inventions None 7, Subject of amendment (1) "Claims in the specification" column (2) "Detailed explanation of the invention in the specification" column 8, Contents of amendment (1) Description 9 amendments have been made to the claims of

(2) Detailed explanation of the invention in the specification (page 7, 15 of the specification)
(Correct the result of further research as the result of further research)
.

(3) Detailed description of the invention in the specification (E!A Specification 22
Page 19, correct CDCl2 to CDC1).

Attachment (1) The scope of the patent claims will be amended as follows.

2. Claims (1) General formula (wherein R4 is a hydrogen atom, a t-butyldimethylsilyl group,
Represents a methoxyethoxymethyl group or a methoxymethyl group, R2 is β-methyl-α having 5 to 18 carbon atoms in the main chain,
Indicates a β-unsaturated fatty acid residue or a linear alkylcarbamate residue having 1 to 18 carbon atoms. ) is a new turtheolide conductor.

(2) The hydroxyl group at the 15th position of the solceolide conductor represented by the general formula (R, It-butyldimethylsilyl group, methoxyethoxymethyl group, or methoxymethyl group) has a main chain of 5 to 18 carbon atoms. esterified with β-methyl-α, β-unsaturated fatty acid or added with a linear alkyl isocyanate having 1 to 18 carbon atoms (wherein R, l They have the same meaning, and R2 represents a β-methyl-α, β-unsaturated fatty acid residue having a main chain of 5 to 18 carbon atoms or a straight-chain alkylcarbamate residue having 1 to 18 carbon atoms. A method for producing a turtheolide derivative represented by .).

(3) A solceolide derivative represented by the general formula (in the formula, 83 represents a t-butyldimethylsilyl group, a methoxyethoxymethyl group, or a methoxymethyl group) has a hydroxyl group at position 15 and has 5 to 18 carbon atoms in its main chain. - Methyl - esterified with α, β-unsaturated fatty acids or completely added with a linear alkyl isocyanate having 1 to 18 carbon atoms to form the general formula (3) (wherein R3 has the same meaning as above). and R2 represents a β-methyl-α, β-unsaturated fatty acid residue having a main chain of 5 to 18 carbon atoms or a linear alkylcarbamic acid residue having 1 to 18 carbon atoms. A method for producing a turtheolide derivative represented by the general formula (wherein R2 has the same meaning as above), which comprises obtaining a compound and then hydrolyzing the same.

(4)

Claims (3)

[Claims] (1) General formula (in the formula, R4 is a hydrogen atom, a t-dityldimethylsilyl group,
Indicates a methoxyethoxymethyl group or a methoxymethyl group, and R2#'i β-methyl-α,β-unsaturated fatty acid residue having 5 to 18 carbon atoms in the main chain or a straight chain having 1 to 18 carbon atoms A new puruseolide haze conductor represented by ・ ) indicating an alkylcarbamate residue. (2) The 15th-position hydroxyl group of the pruseolide cast conductor represented by the general formula (in the formula R, it-zotyldimethylsilyl group, methoxyethoxymethyl group, or methoxymethyl group) is A general formula (in the formula, R3 is It has the same meaning as above, and R2 is a β-methyl-α or β-unsaturated fatty acid residue having 5 to 18 carbon atoms in the main chain or a linear alkylcarpamic acid residue having 1 to 18 carbon atoms. A method for producing a turtheolide derivative represented by: (3) The 15th-position hydroxyl group of the pruseolide conductor represented by the general formula (in the formula, R6 represents a t-butyldimethylsilyl group, a methoxyethoxymethyl group, or a methoxymethyl group) has a main chain carbon number of 5 to 18. is esterified with β-methyl-α, β-unsaturated fatty acid, or added with a linear alkyl isocyanate having 1 to 18 carbon atoms to obtain the general formula (wherein Rs has the same meaning as above). , R2 is a β-methyl-α, β-unsaturated fatty acid residue having a main chain of 5 to 18 carbon atoms or a linear alkylcarbamate residue having 1 to 18 carbon atoms. A method for producing a solceolide derivative represented by the general formula (wherein R2 has the same meaning as above), characterized by: - obtaining the same, and then hydrolyzing the same.