JPS61243099A - Triterpene alcohol organic acid ester and production thereof - Google Patents

Abstract

NEW MATERIAL:An alpha-1-4C alkyl cinnamate having one or two substituent groups of triterpene alcohol on the benzene nucleus, or a benzoic acid ester or cinnamic acid ester having two substituent groups comprising 1-4C alkoxy group and nitro group, amino group, acylamino group, etc., on the benzene nucleus. EXAMPLE:Cycloartenol-3-methoxy-4-propionyloxy-alpha-methyl cinnamate. USE:Antihyperlipemia. PREPARATION:The objective triterpene alcohol organic acid ester can be produced e.g. by reacting (A) triterpene alcohol with (B) acid halogenide of (i) an alpha-1-4C alkylcinnamic acid having one or two substituent groups on the benzene nucleus or (ii) a benzoic acid or cinnamic acid having two substituent groups comprising 1-4C alkoxy group and nitro group, amino group, or acylamino group, etc., on the benzene nucleus.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application: The present invention relates to novel compounds having antihyperlipidemic activity and methods for their preparation. More specifically, the present invention provides excellent antihyperlipidemic activity and low toxicity, i.e., safe and novel alkylcinnamic acids having 1 to 4 carbon atoms, which have triterpene alcohol mono- or di-substituents attached to the benzene nucleus. ester, or a disubstituted group of an alkoxy group having 1 to 4 carbon atoms and a nitro group, an alkoxy group having 1 to 4 carbon atoms and an amino group, or an alkoxy group having 1 to 4 carbon atoms and an acylamino group having 2 to 5 carbon atoms, to benzene The present invention relates to benzoic acid or cinnamic acid esters bound to the nucleus and methods for producing them.

BACKGROUND OF THE INVENTION Hyperlipidemia is well known to be an important risk factor for arteriosclerosis, especially coronary arteriosclerosis.

1975, Miller and old 1ler (G, J, M
iller, N, I! , Mi-11er; La
ncet: Jan, p. 4.16 (1975))
is high-density lipoprotein cholesterol (HDL) in plasma.
-C. ) and the cholesterol pool in the body, and no correlation was observed between blood total cholesterol (hereinafter referred to as TC) and other riboprotein concentrations. He proposed the idea that a decrease in HDL-C concentration leads to a decrease in the clearance of cholesterol from the arterial wall, which promotes arteriosclerosis. Since this report, numerous epidemiological studies [e.g. T, Go
Rdon et al.: As, J. Med, Vol. 62, p. 707 (1977)) reported that the occurrence of ischemic heart disease and HDL-
It has been proven that there is an inverse correlation between C concentration and blood HD
It has been confirmed that a decrease in LC concentration is one of the major risk factors for the development of ischemic heart disease, regardless of the presence or absence of antihyperlipidemic agents.

It has long been known that plant sterols lower serum cholesterol. For example, a mixture of β-sitosterol and dihydro-β-sitosterol (USA, Li
Soysterol, a mixture of plant sterol and tocopherol (Japan, Morishita Pharmaceutical Co., Ltd., trade name: Cytellin), etc. are commercially available as hyperlipidemia therapeutic agents.

On the other hand, the following literature has been published regarding triterpene alcohols.

JP-A-57-18617 discloses that plant sterol 1
When 0.01 to 0.1 part of cycloartenol or 24-methylenecycloartanol is used in combination with the plant sterol, a synergistic effect has been shown to have a stronger serum cholesterol lowering effect than when plant sterol is used alone.

JP-A-58-116415 discloses that 1 to 20 parts of cycloartenol, 24-methylenecycloartanol, or cyclolaudenol is added to 100 parts of plant sterol.
It is stated that when phytosterols are used in combination (particularly about 5 parts), a considerably stronger serum cholesterol lowering effect was observed due to a synergistic effect than when plant sterols are used alone. Especially cycloartenol! :J:, [This shows a synergistic effect of sterols on the serum cholesterol-lowering effect, and 24-methylenecycloartanol and cyclolaudenol show a lower synergistic effect than cycloartenol.

Japanese Patent Application Laid-open No. 59-27824 discloses that cholesterol 0
．． When 1% cycloartenol or 24-methylene cycloartanol was added to the 5% supplemented diet*, the TC reduction rate was 13.7% for the former and 10.2% for the latter compared to the control with high cholesterol intake. Calculated by the present inventors based on the results in Table 2 of the publication).

However, although the aforementioned Sanshin publication reports the effect of lowering serum TO, triglycerides (hereinafter referred to as TG) and total phospholipids (hereinafter referred to as PL) in serum are reported.

), HDL-C, ^theroge-nic Ind
ex (calculated as TC-HDL-C/HDL-C, hereinafter referred to as AI. Some Japanese medical scientists refer to this AI as the cholesterol ratio or arteriosclerosis index.)
There is no description regarding lipid peroxide (hereinafter referred to as LPO). Even though cycloartenol, 24-methylenecycloartanol, and cyclolaudenol reduced serum TC alone or in the coexistence with plant sterols, they are still important in determining the treatment of hyperlipidemia. It also has a lowering effect on the serum lipids TGSPL and LPO, which are items, and also has the effect of increasing HDL-C, which has recently been particularly important in the treatment of hyperlipidemia, and further reducing A]. It is unknown whether they have it or not. Moreover, such general pharmacological activity cannot be estimated.

Furthermore, T-oryzanol, which is currently commercially available in Japan as a therapeutic agent for head and neck injuries, is not a single product, but a mixture of various plant sterols and ferulic acid esters of triterpene alcohols.

An example of this ingredient ratio is campesterol 14%
, stigmasterol 1%, β-sitosterol 4%,
Shifuroa, 2% lutanol, 35% cycloartenol
, 24-methylenecycloartanol, and 44% of each ferulic acid ester, and contains almost no cyclobranol ferulic acid ester.

Recently, the effect of T on cholesterol metabolism in hyperlipidemic rats.
-There is the following report regarding the effects of oryzanol. Fumio Kuzutani, Noriyoshi Yoshimine, Shoji Kato, Katsunari Fujita, Hiroyo Ushigome and others (Ger
Iatric Medicine Volume 1, 519~
p. 524 (1980)) used rats fed a high-cholesterol diet and treated them with 0 γ-oryzanol as a control.
．． In rats fed high cholesterol diets supplemented with 1, 0.5 and 1%, TC was clearly decreased, and the decrease was dose dependent. The rate of decrease in TC exceeded the rate of decrease in PL, and the rate of decrease in TC was equivalent to the rate of decrease in HDL-C, and no effect on AI was observed. It is reported that TG showed an increasing tendency, and LPO clearly showed a decreasing effect.

Mitani Kouga, Kido Yasuhiro, Shimizu Sei-1 Morita Seiji et al.
3)) Compared to rats fed a high-cholesterol diet, rats fed a high-cholesterol diet supplemented with 0.5, 1.0 and 2.0% T-oryzanol had lower serum T levels, respectively.
The C value showed a reduction rate of 8.1.23.4 and 30.9%. On the other hand, no significant decrease was observed in serum TO value and serum PL value.

Shuji Inoue, Masato Eyo, Shinobu Sato et al. [Arteriosclerosis Vol. 11, No. 2, June 41, pp. 7-428 (1983)] investigated the effects of γ-oryzanol on hyperlipidemia in hypothalamically obese rats. However, although T-oryzanol has an effect of lowering blood TC, no significant decrease is observed in blood TO. They also reported that it had no effect on blood PLSHDL-C.

On the other hand, regarding organic acids, R, D, Sharma (^
the-rosclerosis volume 37, 463~
p. 46B (1980) found that ferulic acid (Perultac ac
id) and p-fumaric acid (p-Cous+aric ac
id), the TC decrease rate is 10.8% for the former and 9.4 for the latter.
% significantly decreased. Ferulic acid lowers TG by 18.7
%, p-fumaric acid decreased to 19.8%, but the decrease was not significant. Almost no decrease in PL was observed in both cases. Vanillic acid
reported that no decrease in TC, TG, or LP was observed for caffeic acid and cinnamic acid.

Although not an organic acid alone, the following report has been published regarding the antihyperlipidemic effect of α-methylcinnamic acid derivatives.

Hiroki Takashima et al. (Biochemical Phyvac
Science 27@, p. 2631 (1978)) describes α-mono-p-myristyloxy-α in rats.
We reported on the antihyperlipidemic effect of -methylcinnamoylglycerol.

Ribe Watanabe et al. (Journal of Medicina
l Chemistry vol. 23, p. 50 (1980)
) are p-alkoxycinnamic acid and p-alkoxy-α-
Methylcinnamic acid (however, the alkyl group of alkoxy is methylene, vinyl, and C8-C18: phenyl group); 0-1
p- or m-myristyloxycinnamic acid; m-methoxy-p-alkoxy-α-methylcinnamic acid (however, the alkyl groups of alkoxy are C12 and C14); 1)-alkoxycinnamic acid and p-alkoxy-α-methylcinnamic acid Detailed information on the preparation method of ester derivatives [alkoxy group is methylene, vinyl, methyl, butyl, C8 to C18; ester group is chloroethyl, methacryloxyethyl, monoglyceride, diglyceride, etc.] and their antihyperlipidemic activity. reported. Furthermore, Ribe Watanabe et al. (Special Publication No. 51-45582) p-alkoxy-α-
Methylcinnamic acid (however, the alkyl group of alkoxy is 08-
A method for producing C16) was reported. Tomio Ota et al.
80370) is α-methyl-p-(pyridyl (
or pyridylalkyl)oxy]-cinnamic acid (or a C1-C3 alkyl ester of cinnamic acid), a method for producing the same, and an antihyperlipidemic agent containing the same.

Recently, Helmuth Grill et al.
No. 4) is N-carboxymethyl-4-(2-hydroxy-4-phenylbutoxy)benzamide, 4-(4
(4”-t-butylphenyl)-2-oxobutoxy]
We reported on p-oxybenzoic acid derivatives such as benzoic acid, their production methods, and antihyperlipidemic agents.

Problems to be Solved by the Invention: The present inventors conducted a trial on the antihyperlipidemic effects of known compounds such as cycloartenol, 24-methylenecycloartanol, and cyclobranol. The pharmacological test method for antihyperlipidemia is Method B (initial body weight 100 ± 1
A method in which male Wistar rats (G) were reared for 4 weeks with free access to food and water - hereinafter referred to as Method B. ). For reference, method A of the pharmacological test method for antihyperlipidemia (feed intake was limited to 10 g/day for 1 star male rats with an initial body weight of 100±1 g).

However, water is allowed ad libitum and the rearing period is 2 weeks - hereinafter referred to as Method A. ) is the method adopted in the previous application (Patent Application No. 59-115306, filing date: June 4, 1982), and to distinguish it from this method, it is referred to as method B in the present invention. The method for measuring each lipid component in serum will be described later. The antihyperlipidemic test results of known triterpene alcohols using Method B are shown in Table-
1 and 2.

As can be seen from Tables 1 and 2, the cycloartenol and cyclobranol administration group showed a significant difference (p < 0.01) compared to the control group administered hyperlipidemic feed.
), a decrease in serum TC was observed.

In addition, the 24-methylenecycloartanol administration group also had a significant effect (
A decrease in TC (P < 0.05) was observed. HDL-C
Cycloartenol was significant (P<0.01
), and the decrease in 24-methylenecycloartanol was slight and not significant. On the other hand, cyclobranol showed a slight increasing tendency, but the increase was not significant. It is desirable that this HDL-C increases significantly as shown in the above-mentioned literature. One of the objectives of creating an antihyperlipidemic agent using the compound of the present invention is to significantly lower TC and significantly increase HDL-C in serum.

As shown above, in line with previous literature results, it was confirmed that single doses of known triterpene alcohols such as cycloartenol, cyclobranol, and 24-methylenecycloartanol significantly lowered TC in serum. did. However, regarding HDL-C, the antihyperlipidemia test method conducted by the present inventors in which both Methods A (see patent application No. 115306/1982) and Method B, which differ in rearing conditions, showed no significant results. No increase was confirmed. Regarding AI,
All three types of triterpene alcohols showed a decreasing trend. For TG, PL and LPO, the three triterpene alcohols showed no significant variation. However, in a comparison of these three triterpene alcohols, cyclobranol showed a tendency to decrease TC, AI, TG, PL, and LPO, but it increased HDL-C, and compared with cycloartenol and 24-methylenecycloartanol. showed different action behavior. That is, cyclobranol was found to have a better antihyperlipidemic effect than cycloartenol and 24-methylenecycloartanol.

As a result of detailed studies to improve the antihyperlipidemic effect of triterpene alcohols, the present inventors discovered the existence of a number of novel triterpene alcohol organic acid ester compounds with excellent antihyperlipidemic activity. discovered. That is, the present inventors ideally aim to create an antihyperlipidemic agent that lowers the TC1PLSTG content in serum while increasing the HDL-C content, simultaneously lowering AI, and further lowering the LPO content in the serum. I researched it as a goal. Next, we will discuss the creation of an antihyperlipidemic agent that exhibits clear improvement in antihyperlipidemic effects compared to known triterpene alcohols and T-oryzanol as starting materials in 2 to 3 or more of the 6 measurement items. I considered it carefully. As a result, it has been found that the organic acid ester of triterpene alcohol according to the present invention has excellent antihyperlipidemic effects. This fact is difficult to imagine from the conventionally known properties of triterpene alcohols and organic acids alone or of γ-oryzanol.

Means for solving the problems; The novel triterpene alcohol organic acid esters of the present invention include cycloartenol, cyclobranol, 24-methylenecycloartanol, lanosterol, lanosterol, agnosterol, cyclosadol, dihydroagnosterol, It is an organic acid ester of cycloartanol, cycloartanol, cycloeucalenol, euphor, butyrospermol, circalol 5, euphorbol or damaradienol. Among these, cycloartenol, cyclobranol, 2
It is an organic acid ester of 4-methylenecycloartanol. Preferred organic acids are amino groups, nitro groups, hydroxy groups, acylamino groups having 2 to 5 carbon atoms, alkoxy groups having 1 to 4 carbon atoms, or alkylcarboxy groups having 2 to 6 carbon atoms as a substituent in benzene. α-C1-C4 alkylcinnamic acid bonded to the nucleus; a hydroxy group and a C1-4 alkoxy group, a hydroxy group and a C2-6 alkylcarboxy group, a C1-4 alkoxy group Alkylcarboxy group having 2 to 6 carbon atoms, alkoxy group having 1 to 4 carbon atoms and nitro group, alkoxy group having 1 to 4 carbon atoms and amino group, alkoxy group having 1 to 4 carbon atoms and 2 to 4 carbon atoms
5 acylamino group, 2 of C 1-4 alkoxy group
α-alkylcarboxylic acid having 1 to 4 carbon atoms; carbon ff1M1 having two disubstituents of alkylcarboxy groups having 2 to 6 carbon atoms or two hydroxyl groups bonded to the benzene nucleus;
Cinnamate acid having a disubstituted group of ~4 alkoxy groups and a nitro group, a C1-4 alkoxy group and an amino group, or a C1-4 alkoxy group and a C2-5 acylamino group on a benzene nucleus or benzoic acid; a saturated fatty acid having 4 to 20 carbon atoms.

The compounds of the present invention are stable compounds. As is clear from the production method shown in the examples, it is a stable compound that does not undergo any hydrolysis even when heated and stirred at 60 to 70'C for 3 hours in a strongly acidic aqueous solution with a pH of 0.5 to 1.5.

The structural formulas of three preferred organic acid esters of triterpene alcohols in the compounds of the present invention are shown below.

(Left below) When R is H in general formulas 1a, , Ib, and Ic, formula 1
a is cycloartenol, 21b is 24-methylenecycloartanol, and formula Ic is cyclobranol. These three types of triterpene alcohols are known.

In the present invention, R in Ia, Ib and Ic represents a residue of the various monobasic organic acids shown above.

Among these organic acid residues, 04 to C20, preferably 06
Compounds of the present invention comprising organic acid residues other than residues of saturated basic fatty acids of ~016 are shown in general formulas (1), (2) a to d, and me.

In the general formula, R1 represents an α-C1-C4 alkyl-α, β-unsaturated carbonyl group (-CH=C(R3)-Co-), and R2 represents an amino group (-NH2) or an acylamino group (-N
HCOR3), nitro group (-NO2), 'nee Vo-t
'z group (-OH), alkoxy group having 1 to 4 carbon atoms (-
0R3), or an alkylcarboxy group having 2 to 6 carbon atoms (
-0COR4). R3 is an alkyl group having 1 to 4 carbon atoms, ie methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, S-butyl or t-butyl. R4 is an alkyl group having 1 to 5 carbon atoms, that is, in addition to the above alkyl group having 1 to 4 carbon atoms, pentyl, 130-
Pentyl, S-pentyl, 3-pentyl or t-pentyl. That is, the general formula (IF) is a triterpene alcohol ester of an alkyl silicate having 1 to 4 carbon atoms, in which one substituent of R2 is bonded to the ortho, meta or para position of the benzene nucleus.

General Formula However, R1 and R3 in the general formula m aw d represent the same meanings as above.

General formula: However, R5 of me is an α, β-unsaturated carbonyl group (-
CH=CH-Co-) or a carbonyl group <-CO->, and R3 has the same meaning as above.

The compound of general formula (a) has different disubstituted groups of OH group and OR3 group or OH group and 0COR4 group on the benzene nucleus, and general formula mb
The compound has OR3 groups, 0COR4, NO2 in the benzene nucleus.
, NH2 or NHCOR3 groups are triterpene alcohol esters of α-01-4 alkylcinnamic acid. The compounds ma and l1rb will be explained in detail below.

That is, in the compound shown in the general formula ma, the OH group is bonded to the ortho position (2 position) of the benzene nucleus, Kiniha, OR3
or a compound in which the 0COR4 group is bonded to the 3, 4.5 or 6 position, respectively. Similarly, when the OH group is bonded to the meta position (3rd position) of the benzene nucleus, OR3 group or 0COR4
The groups are compounds bonded to the 2, 4, 5 or 6 positions of the benzene nucleus, respectively. Similarly, when the OH group is bonded to the para-position (4-position) of the benzene nucleus, OR3 group or 0COR
The four groups are compounds each bonded to the 2nd or 3rd position of the benzene nucleus. (Hereinafter, these will be abbreviated as compounds of general formula (1)a.) The individual bonding modes of these ma compound groups are shown in the following general formulas ma1 to I[Ialo.

General formula % formula %) 0H However, in the general formula n[a1 to m a 10, R1 and R3 have the same meanings as above.

The bonding mode for the compound group of the general formula mb is that the OH group of the compound group of the general formula ma is replaced with an OR3 group, and the benzene nucleus has an OR3 group and 0COR4, NO2, NH2
or α-01 binding a different disubstituted group of NHCOR3 group
It is a triterpene alcohol ester of ~4 alkylcinnamic acid. Therefore, ■b1 has an OR3 group instead of the OH group of the compound I[al, and 0COR4, NO2, NH2 instead of the OR3 group or 0COR4 group of the compound DIa1.
Or it is a compound in which three NHCOR groups are alternatively bonded.

The following mb2 to mb10 are the same, and these mb1
The general formula of ~m b 1g is shown below. Below 1[1bl
~I [0COR4, NO2 in the compound group of b to
, NH2 or NHCOR3 groups are collectively referred to as rXJ.

General formula However, in general formulas mb1 to mb10, Rt and R
3 represents the same meaning as above.

The compound of general formula mc is a triterpene alcohol ester of α-01 to 4 alkylcinnamic acid having two OH groups on the benzene nucleus, and the compound of general formula I[Id has two OR3 groups on the benzene nucleus. That is, the compound of general formula (c) has the 2nd and 3rd positions, the 2nd and 4th positions, the 2nd and 5th positions, and the 2nd and 6th positions of the benzene nucleus.
It has two OH groups at the 3rd and 4th positions, or the 3rd and 5th positions, and consists of the following six types of bonds.

Furthermore, the bonding mode of the compound group of the general formula IIId is that two OR3 groups are substituted for the two OH groups of the general formula mc compound, and m
There are 61 compounds of cti to I[d5.

In the group of compounds of general formula I[e, NO2, NH2 or N
When the HCOR3 groups are collectively referred to as rYJ, the bonding mode is I[bl There are 10 types of compounds that are the same as ~m b to.

The method for producing the compound of the present invention will be explained below.

The above-mentioned γ-oryzanol is cycloartenol, 24
- It is a suitable source of methylenecycloartanol and cyclobranol. That is, γ-oryzanol, which is currently commercially available in Japan as a therapeutic agent for head and neck injuries, is not a single product, but a mixture of various sterols and ferulic acid esters of triterpene alcohols. An example of this component ratio is campesterol 14%, stigmasterol 1%, β-sitosterol 4%, cycloartanol 2%.
%, cycloartenol 35%, and 24-methylenecycloartanol 44%.

Isolation method of cycloartenol: That is, T-oryzanol was isolated using acetone-methanol, acetone, and ethyl acetate, with reference to the method of Endo, Misu, Inaba et al. Repeated recrystallization to obtain cycloartenol ferulic acid ester, which was saponified and decomposed to give cycloartenol with a melting point of 1 ol to 102°C and a specific optical rotation [α
] Xi・' +49.7° (C1,01, CICl3
) was obtained. This product showed a single peak in gas chromatography.

Isolation method of 24-methylenecycloartanol: The method was based on the method of Endo et al. [Yuukagaku Vol. 18, pp. 63-67 (1969)]. That is, crystals from the mother liquor in which cycloartenol was separated from γ-oryzanol were acetylated with pyridine-acetic anhydride, and the acetylated product was purified with chloroform-acetic anhydride.
Repeated recrystallization using ethyl acetate-ethanol (4:3:2), deacetylation, recrystallization with acetone-methanol mixed solvent to obtain 24-methylenecycloalknolferulic acid ester, which was saponified and decomposed. Possibly 24-methylenecycloartanol melting point 123
~124℃, specific optical rotation [α] +48.1° (C1
,00,C)IC13) was obtained. This product showed a single peak in gas chromatography.

Isolation method of cyclobranol: 1.1 kg of γ-oryzanol (total amount of cyclobranol 0%) was dissolved in 8β of acetone, 40 g of iodine was added, and after dissolution, the mixture was heated under reflux for 1.5 hours. After cooling, 10% sodium thiosulfate aqueous solution 500% was added and stirred for 30 minutes.
Furthermore, 550 g of water was added and the precipitated crystals were filtered out. Add this to 700-1 of a 2% sodium thiosulfate aqueous solution, followed by 4-4 of water.
2 and dried. As a result of gas chromatography analysis of this T-oryzanol, cyclobranol was found to be about 2
1 kg of γ-oryzanol containing 3% was obtained. 1 kg of this crystal was suspended in 4% caustic ethanol solution 81 and heated under reflux for 3 hours. After cooling, the precipitated potassium salt of γ-oryzanol was collected by filtration, and then methanol 8I
The mixture was suspended in water and heated under reflux for 2 hours. After cooling, the extruded yellow crystals were collected by filtration, dried, and potassium salt of γ-oryzanol 26
Obtained 0g. The crystals were treated as described above with caustic curry ethanol solution at alkali concentrations of 3% and 2%, and yellow crystals 1
30g was obtained. This contained 88% cyclobranol. Subsequently, 130 g of yellow crystals were saponified and decomposed with 2.6 g of a 2N caustic ethanol solution, and the residue was extracted with 1.2 g of chloroform. After drying the chloroform layer, it was distilled off under reduced pressure to obtain 80 g of crude cyclobranol (
A purity of 88%) was obtained. 80 g of this crude crystal was mixed with 1.0 g of acetone.
Repeat recrystallization three times at 61 to obtain cyclobranol crystal 2
8g was obtained. Melting point 165-166°C, specific rotation [α] tube +47.0° (C1, OQ, chloroform). This showed a single peak in gas chromatography.

The triterpene alcohol organic acid ester of the compound of the present invention can be easily obtained by utilizing a known esterification reaction between a general alcohol and an organic acid. Namely, sulfuric acid, P
-) Esterification reaction of an organic acid and triterpene alcohol by dehydration using a catalyst such as luenesulfonic acid or boron Miura (BF3); reaction of an organic acid anhydride and triterpene alcohol in the presence of a catalyst such as sulfuric acid or zinc chloride; Organic acid halide (also called organic acid halide).

The following have the same meaning. ) and a triterpene alcohol. Among these, the most preferred method is the reaction of an organic acid halide with a triterpene alcohol. That is, a monobasic acid of a saturated fatty acid of 06 to 16; among the organic acids of the general formula (2) of the compound of the present invention, the substituent R2 is a NO2 group, an OR3 group, a .0COR4 group, or an NHC
α-01 to 4 alkylcinnamic acid having one substituent group of OR3 group: an organic acid of the compound of the general formula mb with a total of two OR3 groups and 0COR4, NO2, Nl2, or NHCOR3 group; of the compound of the above me OR3 group and NO2 with organic acid,
An organic acid starting from cinnamic acid, benzoic acid, or α-C1-4 alkylcinnamic acid that binds two substituents of the OR3 group, such as a total of two Nl2 or NHCOR3 groups or an organic acid of a IIId compound. In this case, the C0OH group of these organic acids is converted into an acid halide using a halogenating reagent, and then this acid halide is heated in a solvent at a temperature of 10 to 1
By carrying out the esterification reaction at 00°C, a triterpene alcohol organic acid ester having the desired structure could be obtained easily and in high yield. Preferred halogenating reagents include thionyl chloride, sulfuryl chloride, phosphorus pentachloride, phosphorus oxychloride, benzoyl chloride, phthaloyl chloride, hydrogen chloride, and hydrogen bromide. As the dehydrohalogenating agent, pyridine, quinoline, trimethylamine, triethylamine, tripropylamine, tributylamine, magnesium, dimethylaniline, etc. are used.

Of the organic acids of the compound of the present invention of general formula (3), R2 is o
α1 carbon number 1 having one substituent of IH group or Nl2 group
~4 alkylcinnamic acid; OH group and OR3 group, OH group and 0COR like the organic acid of the present invention compound of 11[a]
3 different disubstituents; ■O as in the organic acid of compound c
α1 carbon number 1 to 1 to bond the disubstituent of the H group to the benzene nucleus
When using the alkylcinnamic acid described in No. 4 as a starting material, use an organic acid in which the OH group or Nl2 group has been acylated in advance as a starting material, convert this into an acid halide by the method described above, and then convert it into a triterpene alcohol with the desired structure by the same procedure as described above. It is possible to easily obtain organic acid esters in high yields. After that, OH groups or NH2 groups are bonded to the benzene nucleus by deacylation reaction, that is, heating treatment with a concentrated aqueous solution of ammonia, caustic alkali (caustic soda, caustic potash), or inorganic acid (hydrochloric acid, sulfuric acid, phosphoric acid). Compounds of the general formula (1), (2)a or mc of the compounds of the present invention can be easily synthesized.

The above-mentioned acylation can be easily achieved by using an acylating agent such as an acid anhydride or acid halide of a lower fatty acid such as acetic acid, propionic acid, butyric acid or caproic acid.

In addition, among the compounds of the present invention whose general formulas are ①, mb and me, NH2
One of the groups, NH2 group and OR3 group or NH2 group and 0COR
The compound group of the present invention which has two of the four groups is a triterpene alcohol ester of cinnamic acid, benzoic acid, or α-C1 to C4 alkylcinnamic acid, each of which has a corresponding NO2 group attached to the benzene nucleus, and an acid with iron or zinc. (Hydrochloric acid, sulfuric acid,
Only NO2 groups are selectively reduced to NH2 groups using a reduction method such as acetic acid), tin or tin chloride, and concentrated sulfuric acid. This reduction method of metal and acid is the best reduction method because the unsaturated groups present in the triterpene alcohol group are not reduced.

Next, when the above-mentioned amino signed compound is acylated by a conventional method, one of the NHCOR3 groups to be paired with each other; the present invention which binds two of the NHCOR3 group and the OR3 group, or the NHCOR3 group and the 0COR4 group. The compound is easily obtained.

Effect: The toxicity and antihyperlipidemic pharmacological test results of the compound of the present invention will be explained in detail below.

Acute toxicity test: ctay male mice weighing 30±2g and mice weighing 100±
5 each group of 2g Wistar male rats
An acute toxicity test using oral administration was conducted using rats.

For example, compounds of the present invention for which acute toxicity tests were conducted are shown below.

Practical example 2 (cycloartenol-4-hydroxy-3-
Medoxy α-methyl cinnamic acid ester), Example 4 (
Cyclobranol-4-hydroxy-3-methoxy-α
Example 6 (24-methylenecycloartanol-4-hydroxy-3-methoxy-α-methylcinnamic acid ester), Example 8 (cycloartenol-4-hydroxy-3-
methoxy-α-ethylcinnamic acid ester), Example 28
(Cyclobranol-3-ethoxy-4-hydroxy-
α-methyl cinnamic acid ester), Example 18 (cycloartenol-4-hydroxy-α-ethyl cinnamic acid ester), Example 34 (cycloartenol-4-hydroxy-3
-propoxy-α-methylcinnamic acid ester), Example 55 (cycloartenol-4-amino-3-methoxybenzoic acid ester), Example 61 (cyclobranol-5-amino-2-methoxybenzoic acid ester), Example 77 (cycloartenol-4-amino-3-methoxy-α-methylcinnamic acid ester), Example 65 (
cycloartenol-4-amino-3-methoxycinnamic acid ester), Example 93 (cycloartenol-p-amino-α-methyl cinnamic acid ester), Example 71 (cycloartenol-5-amino-2-nitoxycinnamic acid ester) (acid ester), Example 100 (cycloprano-root amino-α-methyl cinnamic acid ester), Example 79 (24-methylenecycloartanol-4
-amino-3-methoxy-α-methylcinnamic acid ester), Example 85 (24-methylenecycloartanol-5=
Example 59 (cycloartenol-5-amino-2-methoxybenzoic acid ester), Example 58 (cycloartenol-2-methoxy-5-
nitrobenzoic acid ester), Example 66 (cyclobranol-4-amino-3-methoxycinnamic acid ester), Example 83 (cycloartenol-5-amino-2-propoxy-α-methyl cinnamic acid ester), Example 10
1 (24-methylenecycloartanol-m-amino-α-methylcinnamic acid ester), Example 1 (cycloartenol-3-methoxy-4-propionyloxy-α-methylcinnamic acid ester), Example 5 (24- (methylenecycloartanol-3-methoxy-4-propionyloxy-α-methylcinnamic acid ester), and the control drugs cycloartenol, 24-methylenecycloartanol, cyclobranol, and T-oryzanol. The mice (0.1 to 5 g/kg) and rats (2 to 6 g/kg) were dosed individually by gavage with a throat probe in increasing doses from 0.1 to 6 g/kg. During the test period, animals were maintained at an animal room temperature of 22-23° C. and observed for 14 days after dosing. No deaths were observed at the doses administered. Toxicity and behavior after administration were observed over time, but no differences were observed from the normal animal group. In addition, the weight gain was also normal, and there was no difference from the normal animal group. A post-test necropsy did not reveal any macroscopic damage to any part of the main laminar canal. Therefore, it was not possible to determine L Dso values for the compounds of the present invention due to their very low toxicity.

Method B of antihyperlipidemic pharmacology test: 1) Animal: Male Wistar rats weighing 100±1 g were used.

2) Feed: The normal diet was a powdered feed (CE-2) manufactured by Nippon Talea, and the hyperlipidemic diet was a normal diet supplemented with 1% cholesterol and 0.5% cholic acid. The drugs were added to this hyperlipidemic diet at 1% each and administered to rats.

3) Rearing conditions: Groups of 8 animals (however, only the hyperlipidemic diet control group had 16 animals per group) were raised on each diet for 4 weeks.

Two rats were placed in each cage, and food and water were available ad libitum. The animals were kept at a constant temperature of 23±1°C and humidity of 55±5% for 4 weeks. On the 29th day after the start of the experiment (the rats were fasted from water for 16 hours from 4:00 pm on the 28th day to 8:00 am on the 29th day), rats were treated with bentoparbital sodium [trade name: Nembutal]. Blood was collected from the abdominal descending aorta under anesthesia using
, HDL-C, TG.

PL and LPO were measured by the following methods.

Measurement method of serum TC value: TCC Killer-K (Manufacturer: Nippon Shoji Co., Ltd.) was used. The principle of this measurement is that ester cholesterol in serum is hydrolyzed into free cholesterol and fatty acids by cholesterol ester hydrolase, and all of the free cholesterol is oxidized by cholesterol oxidase to produce Δ4-cholestenone and hydrogen peroxide. In this method, phenol and 4-aminoantipyrine are oxidatively condensed using the generated hydrogen peroxide and peroxidase, and the generated red quinone dye is colorimetrically determined using a spectrophotometer at 500 nm to determine the absorbance and TC value.

Preparation of color reagent used: Color reagent: 1 vial (components: cholesterol esterase 25.000 u, cholesterol oxidase 25
(Contains 3.554 μ of u1 peroxidase, 20 μ of 4-aminoantipyrine) Buffer: 33.3 μ of phenol, 489.9 μ of potassium dihydrogen phosphate, and 908.5 μ of sodium phosphate-hydrogen anhydride in 100 μ of ingredients. Dissolved in purified water.

Standard solution: Contains 300 μm of cholesterol in 100% of components.

A solution prepared by dissolving one vial of the coloring reagent in a buffer solution 160 is referred to as the coloring reagent used.

Add 3.0 - of the coloring test solution used to 0.021 R1 of the serum of the specimen, mix well, and after heating at 37° C. for 15 minutes, measure the absorbance with a spectrophotometer at 500 nm. The value is defined as EA. Separately, add 3.0 - of the coloring test solution used to 0.02 - of the standard solution, mix well, heat at 37°C for 15 minutes, and then use a spectrophotometer at 500 nm.
The value obtained by measuring the absorbance at m is defined as ES. This EA and E
Measurement is performed using a blind test of 3.0 liters of the coloring test solution used for both S and S.

Measurement method of serum HDL-C value: Measured by HDL-C Kira t--N (manufacturer: Nippon Shoji Co., Ltd.). That is, very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) in serum are formed into a precipitate by the action of heparin in the presence of calcium ions, and then centrifuged, high-density lipoproteins are dissolved in the supernatant. (H
DL) is dissolved.

The ester cholesterol in this fraction is hydrolyzed to free cholesterol and fatty acids by cholesterol ester hydrolase, and all free cholesterol is oxidized by cholesterol oxidase to produce Δ4-cholestenone and hydrogen peroxide. The total amount of HDL-C was determined by measuring the absorbance at 500 ns+ of the red quinone dye produced by oxidative bonding of phenol and 4-aminoantipyrine using the produced hydrogen peroxide and peroxidase using a spectrophotometer.

Measuring method of serum PL value: Measured by PL Kin)-K (Manufacturer: Nippon Shoji Co., Ltd.). Lecithin, sphingomyelin, and lysolecithin in serum are decomposed by phospholipase D into choline, phosphatidic acid, N-acylsphingosyl phosphate, and lysophosphatidic acid, respectively. The produced choline is oxidized by choline oxidase to quantitatively produce hydrogen peroxide and betaine. The PL content of this hydrogen peroxide was determined by measuring the absorbance at 500 nm of a red quinone dye produced by oxidative condensation of phenol and 4-aminoantipyrine using peroxidase using a spectrophotometric needle.

Method for measuring serum TG value: TG in serum was measured using a triglyceride test kit (manufacturer: Wako Pure Chemical Industries, Ltd.) using acetylacetone. That is, when isopropyl alcohol is added to serum and mixed, proteins are precipitated, lipids and sugars in the serum are transferred to isopropyl alcohol, an adsorbent is added, substances that interfere with coloration are adsorbed, and after centrifugation, the supernatant is When potassium hydroxide is added to a portion, the triglyceride is saponified and glycerin is liberated. Next, a buffer solution is added to adjust the pH to 6, and then a sodium metaperiodate solution is added to oxidize the glycerin into one molecule of formic acid and two molecules of formaldehyde. The generated formaldehyde reacts with acetylacetone and ammonia in the buffer to form a cyclic compound, 3,5-diacetyl-1,4-dihydrortidine (3+5-diacetyl-1+ 4-dihydr).
The triglyceride content was determined by measuring the absorbance of this yellow pigment at 410 nm using a spectrophotometric needle.

Measuring method of serum LPO level: Yagi thiobarbic acid method [Kunito Yagi Bioch-e
n+, Med, Vol. 15, p. 212 (1976), Kunito Yagi, Vitamin Vol. 49, p. 403 (1975)) Lipoperoxide test kit (Manufacturer:
(Wako Pure Chemical Industries, Ltd.). That is, 0.05ml of serum was added to 1.0rnl of physiological saline, stirred gently, and then centrifuged (3,00 rpm, 10 minutes).
and add 4.0% N/12 sulfuric acid to the supernatant. OWI! Add
Mix well. Add 0.5 d of 10% phosphotungstic acid aqueous solution to this, stir well, leave at room temperature for 5 minutes, and centrifuge (3,000 rpm+).

10 minutes). To the obtained precipitate are added 2.0 mm of N/12 sulfuric acid and 0.3 mm of a 10% aqueous phosphotungstic acid solution, and the precipitate is thoroughly suspended using a mixer. Next, centrifugation (3,000
Orpm for 10 minutes), add 4.0 mL of distilled water to the precipitate, and suspend well with a mixer. Next, TBA reagent (5
0% acetic acid solution, containing 2-thiobarbic acid)
1. Add Ome, mix well, place a glass ball on the top of the centrifuge tube, heat in a boiling water bath for 60 minutes, and then cool in running water for 5 minutes. Next, 5.0ml of n-butanol! Add the solution, put on a stopper, mix thoroughly with a mixer for 20 seconds, extract and centrifuge (3,000 rpm, 10 minutes), and measure the fluorescence of the upper n-butanol layer. After adjusting the zero point of fluorescence measurement using a reagent blind test, the standard solution (
1,1,3,3-tetraethoxypropane 5 nmol
/me) 0.1- and the fluorescence intensity (f) of the specimen were measured with a fluorometry needle at an excitation wavelength of 515 nm and a fluorescence wavelength of 553 nm.

That is, in nature, the reaction product of LPO and thiobarbituric acid is the same as the reaction product of malondialdehyde and thiobarbituric acid. Therefore, the concentration of LPO is
It was determined as the amount of malondialdehyde in serum 1-. Standard solutions give malondialdehyde quantitatively 1, 1, 3.
It is an aqueous solution of 5 nmol/- of 3-tetraethoxypropane, and since 0.1- of the standard solution is used for measurement, it is 1.1
．． 0.5 nmol of 3.3-tetraethoxypropane was used, so the LPO content was calculated by the following formula.

LPO content (nmol/-serum) Antihyperlipidemia pharmacological test results: Using rats fed with high cholesterol diet or normal diet, typical compounds of the present invention on serum lipids and serum lipid peroxides, i.e., the same compound as acute toxicity. We will report on the active effects.

The results of the antihyperlipidemia test of cycloartenol, 24-methylenecycloartanol, and cyclobranol used as control drugs are shown in Tables 1 and 2. These effects have been explained above.

Furthermore, the antihyperlipidemic effects of the compounds of the present invention and control drugs cycloartenol, cyclobranol, 24-methylenecycloartanol, and γ-oryzanol according to Method B are shown in Tables 3 to 8.

The control group fed a normal diet showed significant (P < 0.001) decreases in TC, PL, and LPO without exception, compared to the control group fed a hyperlipidemic diet, while HDL-C significantly decreased. (P<0.001). However, although TG showed a decreasing tendency, no significant difference was observed.

In the group to which the compound of the present invention or the control drug was added to the hyperlipidemic feed, a clear improvement in serum lipid components was observed compared to the control group to which the hyperlipidemic feed was administered. In particular, the compound group of the present invention significantly lowered serum lipids such as TC and HDL than the control leaf group.
- Two or more components of C, PL, and LPO were improved.

That is, regarding TC, the control drugs triterpene alcohol and T-oryzanol showed a significant (p<0.01) decrease compared to the control group administered with hyperlipidemic feed. In contrast, Example 2.4.6.7 of the compound of the present invention
7.93.100.79.85.59.66.83 and 101 showed a significant (P < 0.001) decrease, and Example 8.28.18.34.55.61.65
．． Compounds 71.58.1 and 5 were significant (P<0.
01) was observed.

Regarding HDL-C, the control drug cycloartenol showed a significant (P<0.01) decrease, but cyclobranol, 24-methylenecycloartanol, and γ-oryzanol showed a slight tendency to increase or decrease. However, no significant difference was observed. In contrast, Example 2.4.6.28.34.55.61.77.65 of the compound of the present invention.
93, 100 and 101 are significant (P < 0.001
) was observed, and Example 8.18.71.79.85.
Compounds 59.66.83.1 and 5 were significant (P <
The compound of Example 58 showed a significant increase (0.01).
A significant increase (P < 0.05) was observed. Of particular note is Example 4.6.28.55.61.58.66.
Compounds 83 and 101 showed a more significant increase than the normal food administration group.

Regarding AI, both the control drug and the compound of the present invention showed a decreasing tendency, but the compound of the present invention showed a particularly remarkable decrease.

Regarding TG, both the control drug and the compound of the present invention showed a slight to some degree of decreasing tendency, but no significant difference was observed.

Regarding PL, the control drug showed a slight tendency to decrease;
It was not a significant decrease. In contrast, Examples 2.4.6.28.34.59.83 and 101 of the compounds of the present invention
Compounds of Example 8.18.77.93.100.79.85.58 showed a significant (P<0.001) reduction.
Compounds 66.1 and 5 showed a significant (P<0.01) decrease, and compounds of Examples 55.61.65 and 71 showed a significant (P<0.05) decrease.

For LPO, the control drug γ-oryzanol showed a significant (
p < 0.01), and the three types of triterpene alcohols showed a clear decreasing trend, although the decrease was not significant. In contrast, Example 2.4 of the compound of the present invention.
6.8.28.18.34.77.93.100, 71
．． 79.85.59.66.83 and 101 are significant (P
<0.001) was observed, and Example 55.61
．． Compounds 65.58.1 and 5 were significant (P<0.
01) was observed.

As indicated above, the compounds of the present invention often have HDL
-C clearly increases, while TC, AI, PL, LP
A clear downward trend in O was observed. That is, it is clear that the antihyperlipidemic activity of the compound of the present invention is synergistic compared to administration of free triterpene alcohol alone.

Table 9 shows examples of weight gain of rats in this antihyperlipidemia test.
and 10. The weight gain of the normal diet group was significantly higher than that of the control group administered the hyperlipidemic diet (P < 0
．． 001). The group in which the control drug and the compound of the present invention were added to the hyperlipidemic diet showed a slightly smaller tendency to increase than the group administered with the hyperlipidemic diet, but no significant difference was observed.

(Left below) Approximately calculated from the consumption of feed to which the compound of the present invention has been added:
This means that a maximum of 210 μ of the compound of the present invention was administered per rat. For example, cycloartenol-4-hydroxy-3-methoxy-α-methylcinnamic acid ester (Example 2), cyclobranol-3-ethoxy-4-hydroxy-α-methylcinnamic acid ester (Example 28),
Cyclobranol-5-amino-2-methoxybenzoic acid ester (Example 61), cycloartenol-p-amino-α-methylcinnamic acid ester (Example 93) and cyclobranol-m-amino-α-methylcinnamic acid ester The free 4-hydroxy-3-methoxy-α-methylcinnamic acid bound in each 210μ of the acid ester (Example 100) is 70.8μ, 3-ethoxy-4-hydroxyα-
Methylcinnamic acid is 72.5■, 5-amino-2-methoxybenzoic acid is 59.4■, p-amino-α-methylcinnamic acid is 63.4■, m-amino-α-methylcinnamic acid is 62.0■ It is.

Feed containing each of these free organic acids added to the hyperlipidemic feed was administered in the same manner as in the present Hyperlipidemia Test Method B, and the effects were examined.
No antihyperlipidemic effect was observed with these organic acids at doses of 62.0 to 72.5 cm. That is, it was proved that the effect of the compound of the present invention is not due to the organic acid liberated by hydrolysis of the triterpene alcohol organic acid ester.

Among the compounds of the present invention, the most preferred as antihyperlipidemic agents are α-1 to 4-carbon cinnamic acid having one hydroxyl group or amino group attached to the benzene nucleus; It is an ester of a triterpene alcohol of cinnamic acid, cinnamic acid, or benzoic acid having 1 to 4 carbon atoms, which has two groups, a hydroxy group or an alkoxy group having 1 to 4 carbon atoms, and an amino group, attached to a benzene nucleus.

The compounds of the present invention may be administered in the form of oral or parenteral administration for clinical treatment, but oral administration is particularly preferred. Oral dosage forms of the compounds of the present invention include tablets, granules, powders, coatings, sugar-coated tablets, capsules, emulsions, and the like, mixed with suitable pharmaceutical carriers. Examples of pharmaceutical carriers include excipients such as lactose, sucrose, mannitol, glucose, starch, sorbitol, glycine, potassium phosphate, and microcrystalline cellulose; binders such as starch, gelatin, gum acacia, glucose, sucrose, and sorbitol. , mannitol, tragacanth, hydroxypropylcellulose, hydroxypropoxymethylcellulose, carboxymethylcellulose, 2-methyl-5-vinylpyridine-methacrylic acid-
Acrylic acid methyl ester copolymer, polyvinylpyrrolidone, sodium alginate, etc.; Lubricants such as stearic acid, hydrogenated oil, magnesium stearate, calcium stearate, polyoxyethylene monostearate, talc, silicon oxide, polyethylene glycol, etc.;
Examples of disintegrants include potato starch and starch containing surfactants; examples of wetting agents include sodium lauryl sulfate. Furthermore, when administered parenterally, it can also be used as an intramuscular injection drug or a layered preparation. In particular, cocoa butter and Wi tepsol are used as bases for layering agents.
, Subanal, polyethylene glycol, polypropylene glycol, glycerogelatin, gelatin capsules, etc. are used. In addition, known safe preservatives such as methyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, butyl hydroxyanisole, and other safe dyes are used.

Although the dosage of the compound of the present invention varies depending on the method of administration, age, weight, condition, and type of disease of the patient, it is usually preferably about 0.01 g to 5 g per day for humans. Most preferred is 0.02g to 1.5g.

The novel triterpene alcohol organic acid ester shown in the present invention uses the above-mentioned cycloartenol, cyclobranol, and 24-methylenecycloartanol organic acid ester as representative of preferred triterpene alcohol organic acid esters, and uses other than these. lanosterol, lanstenol, agnosterol, cyclosadol (3β-hydroxy-24-methylene-9,19-
Triterpene alcohols such as cyclo-9β-dinoster-23-ene), dihydroergosterol, cycloartanol, cycloartanol, cyclo-ergosterol, euphol, butyrospermol, tirkarol, euphorbol, and damaradienol are shown in the present invention. Also includes organic acid esters of structure. These are preferred as antihyperlipidemic agents. Also, sterols with similar structures to triterpene alcohols, such as dihydro-β-sitosterol, dihydro-T-sitosterol, campesterol, β-
The esters of organic acids shown in the present invention, such as sitosterol, γ-sitosterol, stigmasterol, 24-methylenecholesterol, evisterol, and 22-dihydroergosterol, are expected to exhibit the same effects as antihyperlipidemic agents. . The compounds of the present invention are most preferably used alone, and can also be used as a mixture of two or more.

(Left below) Example 1 Method for producing cycloartenol-3-methoxy-4-propionyloxy-α-methylcinnamic acid 72.0 g (0,272 mol) of 3-methoxy-4-propionyloxy-α-methylcinnamic acid toluene 40
0-1 thionyl chloride 40. Ome (2 equivalents) and 0.5 d of dimethylformamide were added and reacted at 60° C. for 1.5 hours. After concentrating the reaction solution under reduced pressure, dioxane 100Td was added and stirred at 0°C. 80.0 g (0,187 mol) of cycloartenol dissolved in pyridine 300- was added thereto, and the mixture was further heated and stirred at 60°C for 3 hours. . After the reaction was completed, the solvent was distilled off under reduced pressure, and the resulting residue was heated at 800 Wll.
After dissolving in chloroform, the solution was washed with 500 bottles of saturated sodium bicarbonate solution. The aqueous layer is further extracted twice using 500ml of chloroform each time, and the entire chloroform layer obtained is dried, concentrated under reduced pressure, and purified by silica gel column chromatography [solvent: hexane-methylene chloride, (5:1)]. Possibly cycloartenol-3-methoxy-4-
Propionyloxy-α-methylcinnamate ester 11
Obtained 0g.

Yield 87.1%, melting point 130-131℃ Specific rotation [α]
+41.1° (C1,00, CI (C13) elemental analysis result C3□Hbri05 (assuming molecular weight 672.95) Calculated value (%): C78,53H9,59 actual value (%
) :C7B, 59 H9, 52IRI/, KBr
(an″″1):2920.2850.1765.
1710, 1630.1600.1510.1240.
1140.1110°PMR (CDC13) δ: 0
．． 39 (IH, %ABq, 4.2Hz), 0.60
(IB, %ABq, 4.2Hz > , 0.60~
2.20 (2711゜m), 0.90 (6H,
s), 0.98 (6H, s), 1.27 (3H
, t, 7.2Hz), 1.58 (3H, bs),
1.88 (3H, bs), 2.12 (3H, d, 1
．． 2Hz), 2.62 (2H,q,7.2Hz)
, 3.80 (3H, s) , 4.50~5.30 (2
H, n+), 6.80-7.70 (4II+m).

Example 2 Cycloartenol-4-hydroxy-3-
Method for producing methoxy-α-methyl cinnamic acid ester (also known as dichloroartenol-α-methylferulic acid ester) Cycloartenol-3-methoxy-4-propionyloxy-α-methyl cinnamic acid ester 84 obtained by the method of Example 1 .0g-(0,125 mol) to 1000-
After dissolving in dioxane, add 200 rI of 25% ammonia water.
I! was added, and the mixture was heated and stirred at 50°C for 2 hours. After the reaction is complete,
The solvent was distilled off under reduced pressure, and the resulting residue was dissolved in 500T11 chloroform and washed with 500% saturated brine.

The aqueous layer was further extracted twice with 300-ml chloroform,
All the chloroform layers were collected, dried, concentrated under reduced pressure, and the residue was recrystallized from methylene chloride-methanol (1:4) to obtain cycloartenol-4-hydroxy-3-methoxy-α-methylcinnamate (cycloaltenol-4-hydroxy-3-methoxy-α-methylcinnamate). 73.0B of tenol-α-methylferulic acid ester) was obtained.

Yield 94.8%, melting point 143-144℃ Specific rotation [α]
; +44.1° (C1,00, CHCl3 ”
) Elemental analysis results CQ/ H6004 (as molecular weight 616.93) Calculated value (%) jc 79.82 H9,80 actual value (%') jc 79.88 H9,811
RW, KBr (cm-1): 3400.290
0.2850°1695.1690.1625.160
0.1510.1250.1110゜P M R (CD
C13) δ: 0.38 (1B, !/GAB
q, 4.2Hz), 0.59 (III, !4A
Bq, 4.2Hz), 0.60-2.30 (2
7H.

ta), 0.88 (6H,s), 0.97
(6H,s), 1.60 (3H.

bs), 1.66 (3H, bs), 2.12
(3H, d, 1.2Hz), 3.88 (3H,
s), 4.50-5.30 (2H, m), 5.8
0 (IH.

bs), 6.70-7.70 (4H, m).

Example 3 Preparation of cyclobranol-3-methoxy-4-propionyloxy-α-methylcinnamic acid ester 15.59 g (0,059 mol) of 3-methoxy-4-propionyloxy-α-methylcinnamic acid was added to 50 ml of toluene. 20 m (4.6 equivalents) of thionyl chloride and 5 drops of dimethylformamide were added to the suspension and stirred at 60°C for 2 hours. After the reaction, the solvent was distilled off under reduced pressure, and the residue was suspended again in toluene 150- and anhydrous pyridine 3-
Add 20 g (0,045 mol) of cyclobranol to 6
The mixture was stirred at 0°C for 2 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was extracted with 300 mt' of chloroform.

The chloroform layer was washed with water, dried and evaporated under reduced pressure. Add 50rII of ethanol to the residue! and then acetone-water (
19:1) to obtain 24.69 g of cyclobranol-3-methoxy-4-propionyloxy-α-methylcinnamate.

Yield 79.2%, melting point 146-147℃ Specific rotation (α)
, +39.2” (C1,00,CHCl3)
Elemental analysis results c,, H6605 (as molecular weight 686.98) Calculated value (%”): C78,67H9,68 actual value (
%): C7B, 75 H9, 62IRν, K B
r (elm-'): 3400.2590.
2850.1760.1710.1630.1600.
1240.1150.1120゜PMR (CDC13)
δ: 0.37 (LH, ABq, 4.8Hz),
0.62 (18,'A^Bq, 4.8Hz), 0
．． 70-2.22 (27H.

m), 0.92 (6H,s), 0.99 (6
H,s), 1.29 (3H,t, 7.2Hz),
1.64 (9H, s), 2.14 (3H, d, 1
．． 2Hz), 2.63 (2H, q, 7.21 z)
, 3.84 (3H,s) , 4.48~
4.88 (III, m), 6.80-7.08 (3
H, m), 7.59 (11Lq, 1.2Hz).

Example 4 Preparation of cyclobranol-4-hydroxy-3-methoxy-α-methylcinnamic acid ester Cyclobranol-3-methoxy-4-propionyloxy-α-methylcinnamic acid ester obtained by the method of Example 3 24 .69g (0,036 mol) of dioxane 4
00+wl, 40 ml of 25% aqueous ammonia was added dropwise, and the mixture was stirred at 50° C. for 2 hours. After the reaction, the solvent was distilled off under reduced pressure, the residue was washed with ethanol, and then recrystallized from acetone-water (19:1) to give cyclobranol-4-hydroxy-3-methoxy-α-methylcinnabar. 21.72 g of acid ester was obtained.

Yield 95.8%, melting point 185-186℃ Specific rotation [α]
+43.7° (C1,00, cnct3) Elemental analysis result Ca2 Hb> 04 (assuming molecular weight 630.92) Calculated value (%'): C79,95H9,91 Actual value (
%): C79,90H9,98I? , K B r (
cs-'): 3380.2920.2850.1
693.1600.1510.1285.1250.1
120PMR (CDC13') δ: 0.36 (
IIl, ! 4ABq, 4.8Hz), 0.61
(ill, ABq, 4.8Hz), 0.7
6-2.30 (2711°s), 0.91 (
6H,s), 0.99 (6H,s), 1.6
3 (9H.

s), 2.14 (311,d, 1.2Hz
), 3.90 (311,s), 4.48~4
．． 84 (LH, a+), 5.84 (IIL
bs), 6.80-6.98 (311, m)
, 7.55 (IH, q, 1.2Hz).

Example 52 Preparation of 4-methylenecycloartanol-3-methoxy-4-propionyloxy-α-methylcinnamate 0.5 m (2.2 equivalents) of thionyl chloride and 2 drops of dimethylformamide were added and stirred for 2 hours at 60°C. After the reaction, the solvent was distilled off under reduced pressure, and the residue was dissolved again in toluene (2.2 eq.).
- was suspended in 1 ml of anhydrous pyridine, 1 g (0,0023 mol) of 24-methylenecycloartanol was added, and the mixture was stirred at 60°C for 2 hours. After the reaction was completed, the solvent was distilled off under reduced pressure and the residue was extracted with 20ml of chloroform. The chloroform layer was washed, dried, and evaporated under reduced pressure. Ethanol the residue 5WI! After washing with acetone-methanol (
1: Recrystallized from 1) to give 24-methylenecycloartanol-3-methoxy-4-propionyloxy-α-
35 g of methylcinnamic acid ester 1 was obtained.

Yield 86.6%, melting point 134-135℃ Specific rotation [α
); + 41.2° (C1,00,CHCl3
) Elemental analysis value CfvHak05 (as molecular weight 686.98) Calculated value (%); C7B, 67 H9,68 Actual value (%); C7B, 75 H9,62IRν, K
B r (am-'): 3400.2920.
2850.1760.1700.1240.1115゜PMR (CDCl2) δ: 0.36 (IH,〃A
Bq, 4.2Hz), 0.61 (!4ABq, 4.
2Hz), 0.70-2.22 <348, a+
), 0.88 (6H,S), 0.96 (6H,S
) , 1.26 (3H, t, ?, 211z) , 2.
11 (3H, d, 1.2Hz), 2.60 (2H
,q,7.2Hz),3.80(31(,S),4
．． 44-4.86 (IH, a+), 4.86-5.
26 (2B, s), 6. '76-7. OB (3Lw
+), 7.55 (ILq, 1.2Hz).

Example 6 Preparation of 24-methylenecycloartanol-4-hydroxy-3-methoxy-α-methylcinnamate 24-methylenecycloartanol-3-methoxy-4-propionyloxy-α- obtained by the method of Example 5 1.35 g (0,002 mol) of methyl cinnamic acid ester was dissolved in dioxane 20me, and 25% ammonia water 2-
After dropping, the mixture was stirred at 50°C for 2 hours. After the reaction, the solvent was distilled off under reduced pressure, the residue was washed with ethanol, and then recrystallized from ethanol to obtain 1.02 g of 24-methylenecycloartanol-4-hydroxy-3-methoxy-α-methylcinnamate. I got it.

Yield 82.2%, melting point 144-145℃ Specific rotation [α]
Satoshi +44.8° (C1,0O1CIC13) Elemental analysis result Ca3 H6204 (as molecular weight 630.92) Calculated value (%”): C79,95H9,91 Actual value (
%"): C79,99H9,84IRj/, K B
r (an-'): 3400.2900.2
850°1690.1600.1510.1250.1
110°PMR (CDC13) δ: 0.37
(IL %ABq, 4.2Hz >, 0.61 (1
B,! 4ABq, 4.2Hz), 0.70~
2.21 (34H.

m), 0.89 (6H,s), 0.98
(6H,s), 2.14 <3H,d, 1.2Hz
>, 3.88 (3H, s), 4.50-4.
88 (IH, m), 4.88-5.28 (2H
, n+) 1.5.80 (LH, bs), 6
．． 82~7.10 (3H, m),? , 59 (1
)1. q, 1.2Hz).

Example 7 Cycloartenol-4-butyryloxy-
Preparation of 3-methoxy-α-ethylcinnamic acid ester A solution of 18.0 g (0,062 mol) of 4-butyryloxy-3-methoxy-α-ethylcinnamic acid in benzene was cooled to 0°C, and 15.0 m of thionyl chloride ( 3,3
equivalent amount) was added dropwise. This mixture was heated at 60°C for 2 hours. After the reaction, excess thionyl chloride and the solvent were distilled off under reduced pressure, 10rI11 of pyridine and 40-dioxane were added, and 17.5 g of cycloartenol was added while cooling to 0°C.
A solution of pyridine 30 containing (0,041 mol) was added dropwise. This mixture was stirred at 20°C overnight.

After the reaction, the solvent was distilled off under reduced pressure, and the residue was dissolved in chloroform 20
0rII! The chloroform layer was concentrated under reduced pressure, and the obtained crude crystals were mixed with acetone-methanol (1:1).
Recrystallization was performed to obtain 22.4 g of cycloartenol-4-butyryloxy-3-methoxy-α-ethylcinnamate.

Yield 77.9%, melting point 118.5-119.5°C Specific optical rotation [α] Sweet +35.7° (C1,0O1C1(C1
3) Elemental analysis results C44HI, t O5 (assuming molecular weight 701.00) Calculated value (%'): C78,8L H9,78 actual value (%''): C78,72H9,86IRν, K
B r (ca+-1): 3400.2920
．． 2800.1700, 1600.1510.1230
．． 1120°PMR (CDC13) δ: 0.36 (
IH, MABq, 4.2Hz), 0.52-2.26
(29H, m), 0.61 (IH, HABq,
4.2Hz), 0.90 (6H,s), 0.96
(61 (, s) , 1.04 (3H, t, 7.2H
z), 1.18 (3H, t, 7.2Hz), 1.
60 (3H, s), 1.66 (3H, s), 2.
26-2.82 (4H, m), 3.79 (3H,
s), 4.50-4.88 <111. m), 4.8
8-5.28 CILm), 6.70-7.12 (3
H, m), 7.48-7.68 (LH, m).

Example 8 Cycloartenol-4-hydroxy-3-
Preparation of methoxy-α-ethylcinnamic acid ester 22.0 g (0,0314 mol) of cycloartenol-4-butyryloxy-3-methoxy-α-ethylcinnamic acid ester obtained by the method of Example 7 was added to 20 g of dioxane.
It was dissolved in 0rR1, and 20 - 25% concentrated ammonia water was added dropwise. This mixture was heated at 50°C for 5 hours.

After the reaction, the solvent was distilled off under reduced pressure, and the residue was dissolved in chloroform 2
The chloroform layer was concentrated under reduced pressure, and the obtained crude crystals were recrystallized from acetone-methanol (1:1) to give cycloartenol-4-hydroxy-3-
Yield of methoxy-α-ethylcinnamate ester: 17.2
Flirt with g.

Yield 86.8%, melting point 136-137℃ Specific rotation [α]
+41.5° (C1,00,C)IC13) Elemental analysis result H6-04 of C (as molecular weight 630.92) Calculated value (%"): C79,95H9,96 Actual value (
%): C79,90H9,83IRν, KBr
(cm-'): 3400.2B30.170
0.1595.1510.1240.1120゜PMR
(CDC13) δ: 0.35 (IH, AABq
, 4.2Hz), 0.50-2.18 (27■1)
, 0-60 (IH9!4ABq+4.2Hz) ,
0.89 (6H,s), 0.95 (6H,s)
, 1.19 (3H,t, 7.21(z) , 157
(3H,s), 1.65 (31(,s), 2.5
6 (2H, bq, 7.2Hz > , 3.87 (3H
,s) ,4.4'? 'y4.85(IH,n), 4
．． 85-5.24 (IH, m), 5.76 (IH
, bs), 6.96-7.09 (3H, m), 7.
24-7.64 (18, m).

Example 9 Cyclobranol-4-butyryloxy-3
-Production of methoxy-α-ethylcinnamic acid ester A solution of 18.0 g (0,062 mol) of 4-butyryloxy-3-methoxy-α-ethylcinnamic acid dissolved in 40-benzene was cooled to 0°C, and thionyl chloride 15, Om
e (3.3 eq.) was added dropwise. After heating and stirring this mixture at 60°C for 2 hours, excess thionyl chloride and the solvent were distilled off under reduced pressure, 40-pyridine and 40-dioxane were added, and while cooling to 0°C, 18.1 g of cyclobranol was added.
(0,041 mol) was added. This mixture was stirred at 20°C overnight. After the reaction, the solvent was distilled off under reduced pressure, the residue was extracted with 200% chloroform, the chloroform layer was concentrated under reduced pressure, and the resulting crude crystals were extracted with acetone-ethanol (
1:1) to obtain 22.3 g of cyclobranol-4-butyryloxy-3-methoxy-α-ethylcinnamate.

Yield 76.0%, melting point 138-139℃ Specific rotation [α]
+33.7° (C1,00,C:HCl3) Elemental analysis result CψH7a05 (as molecular weight 715.03) Calculated value (%): C78,94H9,87 Actual value (%)
”) :C78,89H9,88■Rν,K B r
(am-'): 3400.2920.2B5
0°1760, 1710.1625.1510.123
0.1120゜PMR (CDC13) δ: 0.36
(1■+V, ABq, 4.8Hz), 0.52~2
．． 22 (29H, m), 0.61 (IH,%^
Bq, 4.8Hz), 0.92 (6H,s), 0
．． 97 (6H, s), 1.03 (3H, t, 7.
2Hz), 1.18 (3H, t, 7.2Hz),
1.60 (9Q, s), 2.22~2.82 (4H
, m), 3.81 (3H, s), 4.48-4.
90(1)1. ll+), 6.70-7.18 (3H
,o+) ,7.40-7.64 (IH+m) Example 10 Cyclobranol-4-hydroxy-3
-Production of methoxy-α-ethylcinnamic acid ester 21.3 g (0,0298 mol) of cyclobranol-4-butyryloxy-3-methoxy-α-ethylcinnamic acid ester obtained by the method of Example 9 was added to 200 g of dioxane.
-, and 25% concentrated ammonia water 201111 was added dropwise. After heating and stirring the mixture at 50°C for 5 hours, the solvent was distilled off under reduced pressure, and the residue was extracted with 200 °C of chloroform. The chloroform layer was concentrated under reduced pressure, and the obtained crude crystals were recrystallized from ethanol to give cyclobranol-4-
Hydroxy-3-methoxy-α-ethylcinnamic acid ester was obtained in a yield of 17.1 g.

Yield 88.9%, melting point 156-157℃ Specific rotation [α]
+37,7° (C1,00, CHCl3) Elemental analysis result C illusion H6qO4 (as molecular weight 644.94) Calculated value (%”): C80,07H10,00 Actual value (%): C80°13 H10,12IRν, KBr
(cm-'): 3400.2930.169
6.1235.1130°PMR (CDC13) δ: 0.38 (IH, M
ABq, 4.8Hz), 0.52-2.22 (27
H, m), 0.62 (IH, zABq, 4.8
Hz), 0.91 (61(,s), 0.97
(6H, s) , 1.21 (3H, t, 7.2H
z), 1.62 (98,s), 2.57 (
2H, bq, 7.2Hz), 3.98 (3H, s)
, 4.48-4.86 (11, m) , 5.7
8 (LH, bs), 6.70~? ,OO(31,
m), 7.53 (LH, m).

Example 11 Preparation of cycloartenol-4-propionyloxy-α-methylcinnamic acid ester 4-propionyloxy-α-methylcinnamic acid 17.6
A solution of g (0,075 mol) in benzene 40rnR was cooled to 0°C, and 18.1m thionyl chloride was added to it.
e (3,3 equivalents) and dimethyl formaldehyde 0.5
- was added dropwise. After heating and stirring this mixture at 60° C. for 2 hours, excess thionyl chloride and the solvent were distilled off under reduced pressure, and 40 me of dioxane and 10 il of pyridine were added! Add
While cooling to 0℃, add 21.3g of cycloartenol (0.
, 050 mol) was added dropwise to the solution. This mixture was stirred at 20°C overnight. After the reaction, the solvent was distilled off under reduced pressure, the residue was extracted with 200 d of chloroform, the chloroform layer was concentrated under reduced pressure, the obtained crude crystals were recrystallized from acetone-ethanol (1:2), and cycloartenol -4-propionyloxy-α-methylcinnamic acid ester was obtained in a yield of 27.0 g.

Yield 83.9%, melting point 87-88℃ Specific rotation (α), + 45.9° (C1,00
, CHCl3) Elemental analysis results C1a H6204 (as molecular weight 642.93) Calculated value (%): C80,33H9,72 Actual value (%)
) :C80,31H9,79IRν,KBr
(am-'): 3400.2920.2850
．． 1760, 1700.1260.1215.1115
°PMR (CDC13) δ: 0.36 (1)1.
%ABq, 4.2■2), 0.52-2.20 (27
H,m), 0.61 (IH,!4ABq,4.2
Hz), 0.89 (6H,s), 0.97 (6
11,s), 1.25 (3H,t, 7.2Hz)
, 1.57 (3H,s) , 1.65 (31(,s
) , 2.10 (3H, d, 1.2Hz) , 2.58
(2TI, q, 7.2Hz), 4.28-4.84
0LH, ++), 4.92-5.240LH, m)
, 6.92-7.09 (2B, m) , 7.11
~7.50 (2H, m), 7.50~7.70 (
11+ta) Example 12 Cycloartenol-4-hydroxy-
Cycloartenol-4-propionyloxy-α-methylcinnamic acid ester obtained by the method of Example 11 27.0
g (0,042 mol) was dissolved in 200 mm of dioxane, and 20 mm of 25% aqueous ammonia was added dropwise. This mixture was heated at 50°C for 2 hours. After the reaction, the solvent was distilled off under reduced pressure, the residue was extracted with 200% chloroform, the chloroform layer was concentrated under reduced pressure, the obtained crude crystals were recrystallized from ethanol, and cycloartenol-4-hydroxy-
α-Methylcinnamic acid ester was obtained in a yield of 20.5 g.

Yield 83.1%, melting point 190-191℃ Specific rotation (α)
, +45.8° (C1,00,C)IC13)
Elemental analysis results CQDH1903 (as molecular weight 586.86) Calculated value (%”): C8186H9,96 actual value (%
): C81,77H9,99IRν, KBr (
a11″″1):3400.2992.2985.17
00.1675.1600.1510,1260.12
00.1170.1120゜P M R (CDC13) δ: 0.36
(10,54ABq, 4.2Hz), 0.52~
2.24 (27H,m), 0.61 (IH,'
A8 to Q, 4.2Hz), 0.90 (6Ls)
, 0.98 (6La) , 1.61 (3H,s
), 1.64 (3H,s), 2.13 (3H,
d, 1.2Hz), 4.50-4.88 (IH
,s), 4.88~5.24 (LH,m)
, 5.88~6.60 (IH, ++), 8.68~
7.12 (2H, m), 7.12~7.50 (1
11, m), 7.50-7.68 (LH, a+)
.

Example 13 Preparation of cyclobranol-4-propionyloxy-α-methylcinnamic acid ester 4-propionyloxy-α-methylcinnamic acid 17.6
g (0,075 mol) in benzene 40r11 and while cooling the solution to 0°C, 18.g thionyl chloride was added.
1me (3.3 equivalents) and 0.5rIl dimethyl formaldehyde were added dropwise. After heating and stirring this mixture at 60°C for 2 hours, excess thionyl chloride and the solvent were distilled off under reduced pressure, and 20 m of dioxane and 40 m of pyridine were added.
Cyclobranol 22.0g (0
,050 mol) was added. This mixture was stirred at 20°C overnight. After the reaction, the solvent was distilled off under reduced pressure, extracted with 200% chloroform, and the chloroform layer was concentrated under reduced pressure.
The obtained crude crystals were recrystallized from acetone-methanol (1:1) to obtain cyclogra. Nor-4-propionyloxy-α-methylcinnamic acid ester was obtained in a yield of 26.3 g.

Yield 80.0%, melting point 107-108℃ Specific rotation [α]
+34.7° (C1,0OSCIC13)ρ Elemental analysis result C1C1Hbt104 (assuming molecular weight 656.95) Calculated value (%'): C80,44H9,82 actual value (
%"): CBo, 39 H9, 77IRJ/, K
Br (elm-'): 3400.2920.
2850.1B60.1710.1630.1260.
1200.1165.1120゜PMR (CDC13)
δ: 0.36 (III, %ABq, 4.8Hz
), 0.61 (IH, %ABq, 4.8112)
, 0.74-2.32 (2711°-) , 0.89
(6H,s), 0.96 (6H,s), 1.2
6 (3H, t, 7.2H2), 1.61 (9H
,s) ,2.10 (3H,d, 1.2Hz)
, 2.58 (2H, q, 7.21 (z) , 4.4
6-4.86 (IH, s+), 6.90-7.5
2 (4H, m), 7.52~7.70 (I
H, m).

Example 14 Cyclobranol-4-hydroxy-α
-Production of methyl cinnamic acid ester 26.3 g of cyclobranol-4-propionyloxy-α-methyl cinnamic acid ester obtained by the method of Example 13
(0,040 mol) was dissolved in 200 d of dioxane, and 20 ml of 25% ammonia water! was dripped. After heating and stirring this mixture at 50° C. for 2 hours, the solvent was distilled off under reduced pressure. The residue was extracted with 200% chloroform, the chloroform layer was concentrated under reduced pressure, and the resulting crude crystals were recrystallized from acetone-methanol (1:1) to give cyclobranol-4-hydroxy-α-methylcinnamate ester. was obtained in a yield of 20.7 g.

Yield 83.1%, melting temperature 203-204℃ Specific rotation [α]
; +46. Oo (C1,00, ClICl3)
Elemental analysis results Ct, tlHbo03 (assuming molecular weight 600.89) Calculated value (%): C81,95H10,0? Actual measurement value (
%) :C81,99H10,07 ■Rν, KBr(
C11''ri: 3400.2920.2850.178
0, 1605.1510.1265.1200.11
70.1125゜PMR (CDC13') δ: 0
．． 36 (IIl, WABq+4.8Hz), 0
．． 61 (1B, !4ABq, 4.8Hz)
, 0.80-2.33 (271°re), 0.
90 (6H,s), 0.98 (611,s)
, 1.60 (9H,s), 2.12 (3H,d,
1.2Hz), 4.08~4.88 (111,s
+), 5.56-5.80 (IH, n+),
6.70~6.92 (2B, s+), 7.12~
7.44 (2H, m), 7.58 (IH, q,
1.2Hz).

Example 15 24-methylenecycloartanol-4-
Process for producing propionyloxy-α-methylcinnamic acid ester In the method of Example 13, 24-
25.8 g of 24-methylenecycloartanol-α-methylcinnamic acid ester was obtained by the same procedure except that methylenecycloartanol was used.

Yield 78.5%, melting point 94-95°C Specific optical rotation [α) +44.2° (C1,00, C
ICl3) Elemental analysis results C-grain H-o4 (assuming molecular weight 656.95) Calculated value (%): C80,44H9,82 Actual value (%)
): C80,48H9,78 Example 16 24-Methylenecycloartanol-4-hydroxy-α-methylcinnamic acid ester 24-methylenecycloartanol-4-propionyloxy-α-methylcinnamate obtained by the method of Example 15 24.0 g (0,036 mol) of acid ester was added to dioxane 2
00-, and 20-25% aqueous ammonia was added dropwise. After heating and stirring this mixture at 50°C for 2 hours, the solvent was distilled off under reduced pressure, and the residue was extracted with 200% chloroform.
The chloroform layer was concentrated under reduced pressure, and the resulting crude crystals were recrystallized from acetone-methanol (1:1) to obtain 24-methylenecycloartanol-4-hydroxy-α-methylcinnamate in a yield of 19.4 g. Ta.

Yield 89.6%, melting point 195-196℃ Specific rotation [α]
, +43.8° (C1,00, CICl3
) Elemental analysis results CSt/Hbo 03 (molecular weight 60
As 0.89) Calculated value (%): C81,95H10,0? Actual measurement value (
%): C81,90H10,14 Example 17 Preparation of cycloartenol-4-butyryloxy-α-ethylcinnamic acid ester 3.50 g of 4-butyryloxy-α-ethylcinnamic acid
A solution of (0,0133 mol) dissolved in benzene 71111 was cooled to 0°C, and thionyl chloride 4.8 me (
5 equivalents) was added dropwise. After heating and stirring this mixture at 60°C for 2 hours, excess thionyl chloride and the solvent were distilled off under reduced pressure, 10ml of pyridine was added, and 2.85g (0,0067 mol) of cycloartenol was added while cooling to 0°C. Containing pyridine Lon1! The solution was added dropwise. Add this mixture to 2
Stirred overnight at 0°C. After the reaction, the solvent was distilled off under reduced pressure,
The residue was extracted with chloroform-40, the chloroform layer was concentrated under reduced pressure, and the obtained crude crystals were recrystallized from acetone-ethanol (1:1) to give cycloartenol-4.
-Butyryloxy-α-ethylcinnamic acid ester was obtained in a yield of 3.63 g.

Yield 80.7%, melting point 88-89°C Specific rotation [α] +41.2° (C1,00, Cl
ICl3) Elemental analysis results C'fHLb O4 (as molecular weight 670.98) Calculated value (%): Cso, ss H9,92 actual value (%): C80,64H9,84IRj/, KBr
(e1m'''1): 3400.2940.2
860.1760.1710.1240.1200.1
170.1125°PMR (CDC13) δ: 0.
36 (IH, !4ABq, 4.2Hz), 0.52
~2.22 (298,01), 0.61 (lit
, 54ABq, 4.2Hz) , 0.90 (6H,
s), 0.96 (6)1. s) , 1.03 (3
H, t, 7.2Hz), 1.18 (3H, t, 7.
2Hz), 1.58 (3H,s), 1.66 (3
H,s), 2.22-2.80 (4H,m), 4
．． 42-4.88 (IH, s+), 4.88-5.2
4 (IH, m), 6.89-7.18 (2H, m
), 7.18-7.46 (2H,s), 7.46
~7.64 (18,l11).

Example 18 Cycloartenol-4-hydroxy-
Production of α-ethyl silicate ester Cycloartenol-4-butyryloxy-α-ethyl cinnamic acid ester 2 obtained by the method of Example 17, OOg
(0,003 mol) was dissolved in 20 ml of dioxane,
25% ammonia water 2- was added dropwise. 50% of this mixture
Heated at ℃ for 5 hours. After the reaction, the solvent was distilled off under reduced pressure,
The residue was extracted with 20-chloroform, the chloroform layer was concentrated under reduced pressure, and the obtained crude crystals were recrystallized from acetone to obtain cycloartenol-4-hydroxy-α-ethylcinnamate in a yield of 1.68 g. Ta.

Yield 93.2%, melting point 162.5-163℃, specific optical rotation [
α] Wisdom +46.1° (C1,00, CICl3'
) Elemental analysis results C, // Hbo O3 (molecular weight 60
As 0.89) Calculated value (%'): C81,95H10,0? Actual value (%): C81, 88H10, 12IRν, KBr
(cm-1): 3300.2920.280
0.1760.1710.1625.1500.128
0.1240.1200゜1165.1120゜P M R (CDCl3) δ: 0.36 (IH
, %ABq, 4.2Hz), 0.52-2.22 (
27)1. m ), 0.61 (IH, %ABq, 4
．． 2Hz), 0.90 (6H,s), 0.96
(6H,s), 1.19 (3H,t, 7.2Hz)
, 1.60 (38,s) , 1.67 (3H,
s), 2.57 (2H, bq, 7.2Hz), 4
．． 47-4.88 (IH, m), 4.92-5.3
2 (IH, m), 6.43-6.67 (18,
m), 6.68-7.04 (2H, m), 7.
12-7.48 (2H, m), 7.52-7.6
9 (ill+m) Example 19 Preparation of cyclobranol-4-butyryloxy-α-ethylcinnamic acid ester 5.25 g of 4-butyryloxy-α-ethylcinnamic acid
(0.02 mol) was dissolved in 10 ml of benzene, and while cooling the solution to 0°C, thionyl chloride 7.3-(5
equivalent amount) was added dropwise. After heating and stirring this mixture at 60°C for 2 hours, excess thionyl chloride and the solvent were distilled off under reduced pressure, 40-pyridine was added to the residue, and while cooling to 0°C, 4.41 g of cyclobranol (0, 001 mol) was added. This mixture was stirred at 20°C overnight. After the reaction, the solvent was distilled off under reduced pressure, the residue was extracted with 60-chloroform, the chloroform layer was concentrated under reduced pressure, the obtained crude crystals were recrystallized from acetone-ethanol (1:1), and cyclobranched. Nol-4-butyryloxy-α-ethylcinnamic acid ester was obtained in a yield of 4.80 g.

Yield 70.1%, melting point 117.5-118℃ Specific optical rotation [
α] Wisdom +38.6° (C1,00, CHCl3)
Elemental analysis results C H&904 (assuming molecular weight 685.00) Calculated value (%): C80,65H10,01 actual value (
%): C80,59H10,06IRν, KBr
(am-'): 3400.2900.2B50
゜1770.1710.1625.1510.1230
．． 1120°PMR (CDC13) δ: 0.36 (
IH-,! 4ABq, 4.8Hz), 0.52-2.
24 (29H, m), 0.61 (if, %
ABq, 4.8fiz), 0.90 (611,s)
, 0.96 (6H, s) , 1.03 (3H, t
, 7.211z) , 1.18 (3H, t, 7.2H
z), 1.59 (9H, s), 2.24-2.82
(41, m), 4.48~4.84 (111, m
), 6.90-7.18 (28, m), 7.18
~7.48 (2H, m), 7.48~7.68 (
IH, m).

Example 20 Cyclobranol-4-hydroxy-α
-Production of ethylcinnamic acid ester 4.11 g of cyclobranol-4-butyryloxy-α-ethylcinnamic acid ester obtained by the method of Example 19
(0,0060 mol) is dissolved in dioxane 30-,
31n1 of 25% concentrated ammonia water was added dropwise. This mixture was heated at 50°C for 5 hours. After the reaction, the solvent was distilled off under reduced pressure, the residue was extracted with 40-chloroform, the chloroform layer was concentrated under reduced pressure, the obtained crude crystals were recrystallized from acetone, and cyclobranol-4-hydroxy-α -Ethylcinnamic acid ester was obtained in a yield of 3.39 g.

Yield 91.9%, melting point 202-203℃ Specific rotation [α]
Wisdom +44.0° (C1,00, ClICl3”)
Elemental analysis results C Umbrella 2 H6203 (as molecular weight 614.92) Calculated value (%'): C82,03H10,16 Actual value (%''): C81,97H10,18IRν, KB
r (cm-'): 3350.2920.28
60.1680.1600.1510.1275.12
45.1200.1170.1130゜PMR(cl)cl3) δ: 0.36 (LH,
'AABq, 4.8Hz), 0.52~2.24 (
27H,m), 0.61 (1B, %ABq, 4
．． 8tlz), 0.90 (68,s), 0.97
(6H,s), 1.19 (38,t, 7.2Hz)
, 1.61 (9H,s) ,2.57 (2H,b
q, 7.2Hz), 4.52-4.84 (LH, m
), 6.43-6.64 (IH, m>, 6.
64~7.02 (2Lm), 7.12~7.48
(2H, m), 7.48~7.67 (LH, m
).

Example 21 Cycloartenol-3-methoxy-4
-Production of valeryloxy-α-propylcinnamic acid ester Cycloalcoal was prepared using the same procedure as in Example 7, except that 17.9 g (0,056 mol) of 3-methoxy-4-valeryloxy-α-propylcinnamic acid was used as the raw material. Tenol-3-methoxy-4-valeryloxy-α-propylcinnamic acid ester was obtained in a yield of 23.2 g.

Yield 77.6%, melting point 113-114℃ Specific rotation [α]
+34.2° (C1,00, CHCl3) Elemental analysis result C9H λo5 (assuming molecular weight 729.06) Calculated value (%): C79,07H9,95 Actual value (%)
): C79,13H9,88 Example 22 Process for producing cycloartenol-4-hydroxy-3-methoxy-α-propylcinnamate Cycloartenol-3-methoxy-4- obtained by the method of Example 21 as a raw material Cycloartenol-4-hydroxy-4-methoxy-α-propylcinnamic acid ester was obtained by the same procedure as in Example 8 except that 23.3 g (0,032 mol) of valeryloxy-α-propylcinnamic acid ester was used. Obtained in 18.1 g.

Yield 87.6%, melting point 122-123℃ Specific rotation [α]
Satoshi +41.2° (C1,0O1CHC13) Elemental analysis result C93H6S/ 04 (assuming molecular weight 644.94) Calculated value (%): C80,07H10,00 Actual value (
%) :C80,14H9,97 fruit jll123
Process for producing cycloartenol-4-capryloxy-3-methoxy-α-butylcinnamic acid ester Except for using 19.2 g (0,0551 mol) of 4-capryloxy-3-methoxy-α-butylcinnamic acid as the raw material. Using the same procedure as in Example 7, cycloartenol-4-capryloxy-3-methoxy-α-butylcinnamate was obtained in a yield of 22.7 g.

Yield 54.4%, melting point 100-101℃ Specific rotation [α]
Satoshi +33.5° (C1,00, CHCl3) Elemental analysis result Cpo H7bOs (as molecular weight 757.11) Calculated value (%'): C79,31H10,12 Actual value (%''): C79,38H10,05 Example 24
Cycloartenol-4-capryloxy- as a raw material for the production of cycloartenol-4-hydroxy-3-methoxy-α-butylcinnamate ester
3-methoxy-α-butylcinnamic acid 24.4g (0,
Cycloartenol-4-hydroxy-3-methoxy-α-butylcinnamic acid ester was obtained in a yield of 17.8 g by the same procedure as in Example 8, except that 032 mol) was used.

Yield 84.4%, melting point 110-111℃ Specific rotation [α]
+40.6° (C1,00, CICl3) Elemental analysis result C<tshiH46o4 (assuming molecular weight 672.99) Calculated value (%'): C80,19H10,10 Actual value (%) =CBo, 24 H10, 05 Example 25
Cyclobranol-4-capryloxy-3 as a raw material for the production of cyclobranol-4-hydroxy-3-methoxy-α-butylcinnamic acid ester
-Methoxy-α-butylcinnamic acid 26.2 g (0.03
Cyclobranol-4-hydroxy-3-methoxy-α-
Butyl cinnamic acid ester was obtained in a yield of 18.4 g.

Yield 80.4%, melting point 132-133°C specific optical rotation [α
] Xi +37.0” (C1,00, CHCl3)
Elemental analysis results CqHb904 (as molecular weight 672.99) Calculated value (%): C80,31H10,18 actual value (%)
:C80,39H10,04 Example 2624-Methylenecycloartanol-4-hydroxy-3-methoxy-α-butylcinnamic acid ester 24-methylenecycloartanol-4-capryloxy-3-methoxy-α-butylcinnamic acid as raw material 26
．． 24-methylenecycloartanol-24-methylenecycloartanol-
4-Hydroxy-3-methoxy-α-butylcinnamic acid ester was obtained in a yield of 18.1 g.

Yield 79.1%, melting point 124-125℃ Specific rotation [α]
+39.8° (C1,00, CHCl3) Elemental analysis result C+H6804 (as molecular weight 672.99) Calculated value (%): C80,31H10,18 Actual value (
%): C80,25H10,22 Example 27 Cycloartenol-3-ethoxy-4-hydroxy-α-methylcinnamate ester as raw material Cycloartenol-3-ethoxy-4-propionyloxy-α-methylcinnamate ester 22.
Cycloartenol-3-ethoxy-4 was prepared using the same procedure as in Example 8 except that 0 g (0,032 mol) was used.
-Hydroxy-α-methyl cinnamic acid ester yield: 15
．． Obtained in 8g.

Yield 78.2%, melting point 132-133℃ Specific rotation [α]
+43.9° (C1,00, CHCl3) Elemental analysis result C-like HA204 (assuming molecular weight 630.92) Calculated value (%”): C79,95H9,91 Actual value (
%”): C79,90H9,99 Example 28 Cyclobranol-3-ethoxy-4=hydroxy-α-
Cyclobranol-3-ethoxy-4-propionyloxy-α-methylcinnamic acid ester as a raw material 21.7
Cyclobranol-3-ethoxy-4-hydroxy-α-methylcinnamic acid ester was obtained in a yield of 16.1 mol by the same procedure as in Example 8, except that 0.031 mol) was used.
Obtained in g.

Yield 80.5%, melting point 174-175℃ Specific rotation [α]
+42.4° (C1,00,CICl3'') Elemental analysis result CJHb5104 (as molecular weight 644.94) Calculated value (%): CBo, 07 H10,00 actual value (%''): CBo, 18 H10,05 implementation Example 29 22.2 g of 24-methylenecycloartanol-3-ethoxy-4-hydroxy-α-methylcinnamate 24-methylenecycloartanol-3-ethoxy-4-propionyloxy-α-methylcinnamate as raw material ( 24-methylenecycloartanol-3-ethoxy-4-hydroxy-α-methylcinnamic acid ester was obtained in a yield of 16.7 g by the same procedure as in Example 8, except that 0.0317 mol) was used.

Yield 81.6%, melting point 134-135℃ Specific rotation [α]
+40.2° (C1,00, ClICl3) Elemental analysis result Co3H6604 (as molecular weight 644.94) Calculated value (%): C80,07H10,00 Actual value (
%): C80,13H9,92 Example 30 Cycloartenol-3-ethoxy-4-hydroxy-α-
Cycloartenol-4-butyryloxy- as a raw material for the production of ethylcinnamic acid ester
21.5 g of 3-ethoxy-α-methyl cinnamic acid ester
Cycloartenol-3-ethoxy-4hydroxy-α-ethylcinnamate was obtained in a yield of 15.4 g using the same procedure as in Example 8, except that (0,030 mol) was used.
I got it.

Yield 79.6%, melting point 124-125℃ Specific rotation [α]
+41.2° (C1,00, ClICl3) Elemental analysis results Cy3 Hb'l O4 (molecular weight 644.
94) Calculated value (%”): C80,07H10,00 Actual value (%): C80,04H10,08 Example 31
Cycloartenol-3-ethoxy-4-hydroxy-
Process for producing α-propylcinnamic acid ester Cycloartenol-3-ethoxy-4-valeryloxy-α-propylcinnamic acid ester 26. O
Cycloartenol-3-ethoxy-4-
Hydroxy-α-propylcinnamate ester 16.8g
I got it.

Yield 72.8%, melting point 111-112℃ Specific rotation [α]
+40.7" (C1,00, CICl3) Elemental analysis results Cq%t Hbb O4 (molecular weight 658.
97) Calculated value (%): C80, 19HIG, 10 actual measurement value (
%): C8Q, 26 H10,02 Example 32
Cyclobranol-3-ethoxy-4-hydroxy-
Cyclobranol-3-ethoxy-4-valeryloxy-α-propylcinnamic acid ester 24.2g as a raw material for the production of α-propylcinnamic acid ester
16.7 g of cyclobranol-3-ethoxy-4-hydroxy-α-propylcinnamic acid ester was obtained by the same procedure as in Example 8 except that (0,032 mol) was used.

Yield 72.8%, melting point 134-135℃ Specific rotation [α]
+37゜1' (C1,00, CICl3) Elemental analysis result Cttt H6904 (assuming molecular weight 672.99) Calculated value (%): C80,3L H10,18 actual value (%): C8 (1,25I (10, 24 Example 3
3 Cycloartenol-4-capryloxy- as a raw material for the production of cycloartenol-3-ethoxy-4-hydroxy-α-butylcinnamate ester
3-Ethoxy-α-butylcinnamate ester 23.1
Cycloartenol-3-ethoxy-4-
16.2 g of hydroxy-α-butylcinnamic acid ester was obtained.

Yield 80.2%, melting point 99-100°C Specific rotation [α] +40.0° (C1,00, CI
Cl3'') Elemental analysis results C<tsHb 04 (assuming molecular weight 672.99) Calculated value (%): C80,3L H10,18 Actual value (%): CBo, 2L H10,22 Example 3
4 Cycloartenol-4-propionyloxy-3-propoxy-α-methylcinnamic acid ester as a raw material for the production of cycloartenol-4-hydroxy-3-propoxy-α-methylcinnamic acid ester 23
．． Cycloartenol-4-human μxy 3-propoxy α-methylcinnamic acid ester 17.
2g was obtained.

Yield 80.8%, melting point 138-139℃ Specific rotation (α)
+43.7° (C1,00, CHCl3) Elemental analysis result C,, aH6,04 (as molecular weight 644.94) Calculated value (%): C80,07H10,00 Actual value (
%'): CBo, 19 H10,04 Example 35
Cycloartenol-4-propionyloxy-3-butoxy-α-methylcinnamic acid ester as a raw material for the production of cycloartenol-4-hydroxy-3-butoxy-α-methylcinnamic acid ester 22.
Cycloartenol-4-hydroxy-
3-butoxy-α-methylcinnamate ester 16.5g
I got it.

Yield 78.2%, melting point 126-127℃ Specific rotation [α]
+39.7° (C1,00, CICl3) Elemental analysis result Cita H66o4 (as molecular weight 658.97) Calculated value (%): C80,19H10,10 Actual value (
%"): C80,24H10,03 Example 3624
-methylenecycloartanol-4-butyryloxy-
24-methylenecycloartanol 18.1 as a raw material for the production of 3-methoxy-α-ethylcinnamic acid ester
24-methylenecycloartanol-4-
22.8 g of butyryloxy-3-methoxy-α-ethyl biarsenic acid ester was obtained.

Yield 77.8%, melting point 127-128℃ Specific rotation [α]
Satoshi +35.1° (C1,0O1C)IC13) Elemental analysis result C<t7 H7605 (as molecular weight 715.03) Calculated value (%): C78,94H9,87 Actual value (%)
): C78,90H9,79 Example 3724-Methylenecycloartanol-4-hydroxy-3-methoxy-α-ethylcinnamic acid ester 24-methylenecycloartanol-4-butyryloxy-3-methoxy-α- as a raw material 17.3 g of 24-methylenecycloartanol-4-hydroxy-3-methoxy-α-ethyl cinnamic acid ester was prepared using the same procedure as in Example 10 except that 21.5 g (0,0301 mol) of ethyl cinnamic acid ester was used. I got it.

Yield 89.1%, melting point 137-138℃ Specific rotation [α]
+40.7° (C1,0O1CHC13) Elemental analysis result C,3H6ri04 (as molecular weight 644.94) Calculated value (%): C80,07H10,00 Actual value (
%): C80,1L H9,93 Example 38
Cyclobranol-4-hydroxy-3-propoxy-
Cyclobranol-4-butyryloxy-3 as a raw material for the production of α-ethylcinnamic acid ester
-Propoxy-α-ethyl biarsenic acid ester 22.1g
Cyclobranol-4-hydroxy-3-
17.8 g of propoxy-α-ethyl biarsenic acid ester was obtained.

Yield 89.1%, melting point 140-141℃ Specific rotation (α)
! +36.8° (C1,00, CHCl3)
Elemental analysis result C4rH6204 (as molecular weight 672.99) Calculated value (%): C80,31H10,1B actual value (
%) :C80,36H10,12 fruit) lJ39 2
4-methylenecycloartanol-4-hydroxy-3
-Production method of propoxy-α-propylcinnamic acid ester Example except that 23.5 g (0,0305 mol) of 24-methylenecycloartanol-3-propoxy-4-valeryloxy-α-propylcinnamic acid ester was used as the raw material. 24-methylenecycloartanol-4-hydroxy-3=propoxy-α-
17.2 g of propylcinnamic acid ester was obtained.

Yield 8261%, melting point 120-121℃ Specific rotation [α]
Sweet 39.1° (C1,0OSCIC13) Elemental analysis result C<t(, H7o04 (as molecular weight 687.02) Calculated value (%): C80,41H10,27 Actual value (%)
:C80,32H10,34 Examples 40-42
Preparation of cycloartenol, cyclobranol or 24-methylenecycloartanol-3-propionyloxy-α-methylcinnamate Cycloartenol (21.3g), cyclobranol (22.0g) or 24-methylenecyclo 0.050 mol each of altanol (22,0 g) and 17.6 g of 3-propionyloxy-α-methylcinnamic acid (0,0
75 mol) was used, but the same procedure as in Example 11 was used to obtain the desired target compounds. The yield (%), melting point (℃), specific optical rotation ([α] (C1,00
, CHCl3)) were as follows.

Examples 43 to 45 Preparation of cycloartenol, cyclobranol or 24-methylenecycloalknol-3-hydroxy-α-methylcinnamic acid ester Using 0.042 mol of each of the compounds of Examples 40 to 42, Example The title compound was obtained by the same procedure as in Example 12. The yield (%), melting point (°C), and specific optical rotation ([α](C1,00SCHC13)) of these were as follows.

Examples 46-48 Preparation of cycloartenol, cyclobranol or 24-methylenecycloartanol-3-butyryloxy-α-ethylcinnamic acid ester 3.50 g of 3-butyryloxy-α-ethylcinnamic acid
(0,0135 mol) and cycloartenol 2.85 g
, 2.95 g of cyclobranol, or 2.95 g of 24-methylenecycloartanol, each of which was used in an amount of 0.0067 mol, was carried out in the same manner as in Example 17 to obtain the target compounds described. These yields (%), melting points (℃
), specific optical rotation ((α) v(C1,0O1CIC13)
) were as follows.

Examples 49-51 Preparation of cycloartenol, cyclobranol or 24-methylenecycloartanol-3-hydroxy-α monoethylcinnamate except that 0.003 mol of each of the compounds of Examples 46-48 was used. By the same procedure as in Example 18, the title compound was obtained. These yields (%), melting points (℃)
, the specific optical rotation ([α] (CL, 0O1CHC13)) is as follows.

Examples 52-53 Process for producing cycloartenol or cyclobranol-2-hydroxy-α-methylcinnamate 21.3 g of cycloartenol or cyclobranol 2
2.0 g of each 0.050 mol and 17.6 g (0,075 mol) of 2-propionyloxy-α-methylcinnamic acid.
Cycloartenol or cyclobranol-2-propionyloxy-α-methylcinnamic acid ester was prepared at 27% by the same procedure as in Example 11, except that
．． 5g (yield 85.5%) and 27.5g (yield 8
2.8%). Example 1 using 24.5g each of these
Cycloartenol or cyclo7 by the same procedure as 2.
'-7 nor-2-hydroxy-α-methyl cinnamic acid ester was obtained. The yield (%), melting point (°C), and specific optical rotation ([α] (C1,00, CHCl3)) of these are as follows.

(Left below) Example 54 Cycloartenol-3-methoxy-4
-Production of nitrobenzoic acid ester 3-methoxy-4-nitrobenzoic acid 15. Og(0,0
76 mol) to thionyl chloride 34r! I! (6 equivalents) and 0.5 ml of dimethylformamide! 2 at 60℃
The mixture was heated and stirred for hours. After concentrating the reaction solution under reduced pressure, dioxane 75
TIi was added and stirred at 0°C, and 25.0 g of cycloartenol (0,0
59 mol) was added thereto, and the mixture was stirred at 70°C for 20 minutes. After the reaction was completed, the solvent was distilled off under reduced pressure, and the resulting residue was dissolved in chloroform, washed with saturated aqueous sodium bicarbonate, and then dried.

The chloroform layer was concentrated under reduced pressure, and the residue was recrystallized from methylene chloride-methanol (1:2) to obtain 30.5 g of cycloartenol-3-methoxy-4-nitrobenzoic acid ester.

Yield 85.3%, melting point 182-183℃ Specific rotation [α]
Tube +57.7° (C1,00, CICl3) Elemental analysis result C stop) (rrNO5 (as molecular weight 605.82) Calculated value (%): C75,33H9,15N 2.31
Actual value (%): C75,42H9,07N 2.
36IRν, KBr (am-1): 29
40.1720.1610.1530.1410.13
50.1310.1290.1245゜PMR (CDC
13”) δ: 0.38 (IH, WABq, 4.
2Hz), 0.62 (IH, !4ABq, 4.2H
z), 0.50-2.36 (27H.

m), 0.95 (IH,s), 0.97 (3
H,s), 1.04 (3H,s), 1.60 (3
H,s), 1.69 (3H,s), 4.00 (
3H,s), 4.50-5.32 (2H,m),
7.42-8.01 (3H, m).

Example 55 Cycloartenol-4-amino-3-
Cycloartenol-3-methoxy- obtained in Example 54 of the method for producing methoxybenzoic acid ester
4-nitrobenzoic acid ester 40.0g (0,066
Add 400-mol of acetic acid and 400-mol of dioxane to 0℃
While stirring, add 22 m of 6N-hydrochloric dioxane (
2 equivalents) and 40 g of zinc powder were added, and stirring was continued at 25° C. for 2 hours. After the reaction, the zinc powder is filtered off, the filtrate is concentrated under reduced pressure, the resulting residue is extracted with chloroform, the chloroform layer is washed with water, then saturated sodium bicarbonate solution, dried and concentrated, and the residue is chlorinated. Cycloartenol-4-amino-3 was obtained by recrystallizing with methylene-methanol (1:2).
-Methoxybenzoic acid ester (32.0 g) was obtained.

Yield 84.1%, melting point 186-188℃ Specific rotation [α]
Suga・S+64.3° (C1,00, CICl3) Elemental analysis result C39Hr7N O3 (as molecular weight 575.83) Calculated value (%"): C79,26H9,98N 2
．． 43 Actual value (%): C79,32H9,99N
2.39IRν, KBr (am-'):
3450.3350.2930.1700.1620
．． 1520.1460.1305.1285.12eo
.

1220.1180.1105゜PMR (CDC13') δ: 0.36 (IO,
〃ABq, 4.2Hz), 0.61 (1B, 54
ABq, 4.2Hz), 0.48-2.39 (2
7H.

ta ), 1.61 (3H,s), 1.67 (
3H,s), 3.88 (3H.

s), 4.20 (2H, bs), 4.51-5
．． 31 (2Lm), 6.46~6.77 (LH,m
), 7.30-7.71 (2H, a+).

Example 56 Cyclobranol-3-methoxy-4-
Preparation of nitrobenzoic acid ester 3-methoxy-4-nitrobenzoic acid 50. Og(0,2
54 mol) to 60 ml of thionyl chloride! (3,2 equivalents)
and 0.5 yl of dimethylformamide were added, and the mixture was heated and stirred at 60°C for 2 hours. After concentrating the reaction solution under reduced pressure, 100-dioxane was added and stirred at 0°C, and 93.0 g (0,2
11 mol) was added thereto and stirred at 70°C for 30 minutes.

After the reaction was completed, the solvent was distilled off under reduced pressure, and the resulting residue was dissolved in chloroform, washed with saturated aqueous sodium bicarbonate, and then dried. The chloroform layer was concentrated under reduced pressure and the residue was recrystallized with chloroform-ethanol (1:3) to obtain cyclobranol-3-methoxy-4-nitrobenzoic acid ester (94.4%).
I got g.

Yield 72.1%, melting point 213-214℃ Specific rotation [α]
Tube +53.9° (C1,00, CICl3 > Elemental analysis result C39Hr7N OS (assuming molecular weight 619.85) Calculated value (%): C75,57H9,27N 2.
26 Actual value (%): C75,63H9,22N
2.33IRν, KBr (cm-'):
2930.1715.1610.1530.1410.
1360.1310.1285.1240゜P M R
(CDC13) δ: 0.39 (LH, AABq,
4.8Hz), 0.62 (IH, 54ABq, 4.
8Hz), 0.50-2.28 (27H.

m), 0.92 (61,s), 0.99
(3H,s), 1.05 (31,s), 1.63
(9H,s) ,4.01 (3H,s) ,4
．． 62-5.03 (LH, m), 7.48-7.
96 (3H, a).

Example 57 Preparation of cyclobranol-4-amino-3-methoxybenzoate 94.3 g (0,
152 mol) of acetic acid 1.2β and tetrahydrofuran 1.
21, and 6N-hydrochloric acid-dioxane 100-
and 94 g of zinc powder were added and stirred at 25° C. for 2 hours. After the reaction was completed, the zinc dust was filtered off, the filtrate was concentrated under reduced pressure, and the resulting residue was extracted with chloroform.

The chloroform layer was washed with water and then with saturated sodium bicarbonate solution, dried and concentrated, and the residue was diluted with chloroform-ethanol (1:4
) to obtain 64.2 g of cyclobranol-4-amino-3-methoxybenzoic acid ester.

Yield 71.5%, melting point 235-236℃ Specific rotation [α]
Tube +60.8° (C1,00SCHCI:s) Elemental analysis result C39Hr7 N O3 (molecular weight 589.
86) Calculated value (%): C79.4L H10.08N
2.37 Actual value (%): C79,49H10,
12N 2.42IRν, K B r (aa-')
: 3450.3350.2900.1680.1
620.1310.1280.1260.1110゜P
MR (CDC13) δ: 0.36 (LH,%AB
q, 4.8Hz), 0.61 (11,% ABq, 4
．． 8Hz), 0.50-2.20 (27H.

w+ ), 0.89 (6H,s), 0.96 (
3H,s), 1.01 (3H.

s), 3.85 (3H, s), 3.92-4.
36 (2H, bs), 4.51-4.91 (IH
, a) , 6.42-6.72 (IH, m) , 7.
26-7.72 (2H, a+).

Example 58 Cycloartenol-2-methoxy-5
-Production method of nitrobenzoic acid ester 2-methoxy-5-nitrobenzoic acid 17.3g (0,0
88 mol), 65 me (10 equivalents) of thionyl chloride and 0.3 ml of dimethylformamide! 1 at 50℃.
．． Stirred for 5 hours. After concentrating the reaction solution under reduced pressure, dioxane 1
25m1! was added and stirred at 0℃, and pyridine 125
25.0 g of cycloartenol (0,0
59 mol) was added dropwise, and the mixture was stirred at 60°C for 1.5 hours.

After the reaction was completed, the solvent was distilled off under reduced pressure, the residue was extracted with chloroform, the chloroform layer was washed with water and then with saturated sodium bicarbonate solution, dried and concentrated, and the residue was extracted with methylene chloride-hexane (
1:3) to obtain 31.5 g of cycloartenol-2-methoxy-5-nitrobenzoic acid ester.

Yield 88.7%, melting point 186-187℃ Specific rotation [α]
Tube +43.9° (C1,0OSCIICI3) Elemental analysis result C39HerNOs (molecular weight 605.
82) Calculated value (%”): C75, 33H9, 15N 2
．． 31 Actual value (%'): C75, 30H9, 22
N 2.29IR $7, l (13r (cm-li: 2
930.1695.1610゜1520.1340.1
280.1135°PMR (CDCl2) δ: 0
．． 39 (LH1%ABq, 4.2Hz), 0.62
(IH, AABq, 4.2Hz), 0.50-2
．． 40 (2711゜m), 0.90 (3H,s
), 0.96 (6H,s), 1.01 (3H,
s), 2.60 (3H, bs), 2.68 (3
H, bs), 4.00 (3H, s), 4.65~
5.30 (2H, m), 7.08 (IH, d, 9
．． 411z), 8.34 (IH, dd, 3.0Hz,
9.4Hz), 8.64 (LH, d, 3.0H
z).

Example 59 Cycloartenol-5-amino-2-
Cycloartenol-2-methoxy- obtained in Example 58 of the method for producing methoxybenzoic acid ester
5-nitrobenzoic acid ester 34.0g (0,056
6 mol) was suspended in 1.21 mol of acetic acid at 20°C, and 6 mol)
19 m (2 equivalents) of N-hydrochloric acid-dioxane and 68 g of zinc powder were added and stirred at 30°C for 1 hour. After the reaction was completed, the zinc dust was filtered off, the filtrate was concentrated under reduced pressure, and then extracted with chloroform. After washing the chloroform layer with water and then with saturated sodium bicarbonate solution,
Dry, concentrate, and dissolve the residue in methylene chloride-hexane (1:
4) to obtain cycloartenol-5-amino-
27.2 g of 2-methoxybenzoic acid ester was obtained.

Yield 84.4%, melting point 180-182℃ Specific rotation [α]
Tube・5+47.8° (C1,00, ClICl3)
Elemental analysis results N03 compared to Cl9 (as molecular weight 575.83) Calculated value (%): C79,26H9,98N 2.
43 Actual value (%'): C79, 32H9, 94N
2.41TRV, KBr (cm-1): 3
450,3350.2900.2860.1690,1
630.1500, 1440.1300, 1270.1
245°PMR (CDC13) δ: 0.3B (Ill,
"A^Bq, 4.2Hz), 0.59 (LH,
%ABq, 4.2Hz), -0,50~2.30
(27H.

m), 0.90 (6H,s), 0.93
(6H,s), 1.59 (3H.

bs), 1.67 (3H, bs), 3.55
(2H, bQ) , 3.88 (3■, s) , 4
．． 50-5.30 (2H, m), 6.68-7.
24 (38, ff1).

Example 60 Cyclobranol-2-methoxy-5-
Process for producing nitrobenzoic acid ester 11.6 g (0,0
20ml of thionyl chloride and 0.2ml of dimethylformamide were added to the mixture (59mol) and stirred at 50°C for 2 hours.

After concentrating the reaction solution under reduced pressure, 150rn1 of toluene and 30ml of pyridine were added, and 20g of cyclobranol (0,
045 mol) was added thereto and stirred at 60°C for 2 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was extracted with chloroform. The chloroform layer was washed with water and then with saturated saline, and after drying and concentration, the residue was diluted with chloroform-ethanol (1
: 3) to obtain 25.9 g of cyclobranol-2-methoxy-5-nitrobenzoic acid ester.

Yield: 92. O%, melting point 207-208℃ Specific optical rotation [α]
+32.5° (C1,00, CHCl3) Elemental analysis result C3 HP7N OS (as molecular weight 619.85) Calculated value (%): C75,57H9,27N 2.
26 Actual value (%): C75,52H9,34N
2.30IRJ/, KBr (cm-'): 2
930.1700.1610゜1520.1345.1
280.1130°PMR (CDC13) δ: 0.
39 (11,% ABq, 4.8Hz), 0.62
(1)1. %ABq, 4.8Hz), 0.76~
2.24 (271°n+), 0.91 (3H,
s), 0.96 (6H,s), 1.01 (3H
,s), 1.63 (9H,s), 4.01 (3H
,s) ,4.64~5.02 (1)1,m) ,7
．． 06 (IH, d, 9.6Hz), 8.34 (I
H, dd, 9.6Hz.

3.6Hz), 8.67 (Iff, d, 3.6H
z).

Example 61 Preparation of cyclobranol-5-amino-2-methoxybenzoic acid ester Cyclobranol-2-methoxy-5 obtained in Example 60
25.0 g (0,040 mol) of -nitrobenzoic acid ester was suspended in 1β acetic acid, and 21 m of 6N-hydrochloric acid-dioxane and 25.0 g of zinc powder were added thereto and stirred at 30° C. for 2 hours. After the reaction was completed, the zinc dust was filtered off, the filtrate was concentrated under reduced pressure, and then extracted with chloroform. The chloroform layer was washed with water and then with saturated sodium bicarbonate solution, dried and concentrated, and the residue was recrystallized from chloroform-ethanol (1:2) to obtain cyclobranol-5-amino-2-methoxybenzoic acid ester 13. .7g was obtained.

Yield 57.5%, melting point 193-195℃ Specific rotation [α]
Suga・5+41.5° (C1,00, CHCl3) Elemental analysis results C); + Ht7 N O3 (molecular weight 58
9.86) Calculated value (%): C79.4L HIQ, 08
N 2.37 Actual value (%): C79,35H1
0.15N 2.35IR4, K B r (am-
1): 3430.3350.2930.1690
．． 1500.1460.1430.1310.1270
．． 1245゜PMR (CDC13) δ: 0
．． 36 (LH,!4ABq+4.8Hz), 0
．． 61 (IH, %ABq, 4.8Hz), 0.5
0~2.28 (2711゜m), 0.92 (3
11,s), 0.96 (6H,s), 1.00
(3H.

s), 1.64 (9H, s), 2.88-3.
26 (2H, n+) , 3.81 (3H, s) , 4
．． 52-5.02 (1)1. m), 6.74-6.
90 (IH, +n), 7.08~7.22 (2H
, a+).

) [Examples 62 to 64 Preparation of cycloartenol, cyclobranol or 24-methylenecycloartanol-3-methoxy-4-nitrocinnamic acid ester 17.0 g of 3-methoxy-4-nitrocinnamic acid (0,0
76 mol) and 0.059 mol each of 25.0 g of cycloartenol, 26.0 g of cyclobranol, or 26.0 g of 24-methylenecycloartanol were used to obtain the title compound by the same procedure as in Example 54. I got it. These yields (%), melting points ('c) and specific optical rotations ((z
) 9 (C1,00, CHCl3) was as follows.

(Left below) Examples 65 to 67 Process for producing cycloartenol, cyclobranol or 24-methylenecycloartanol-4-amino-3-methoxycinnamic acid ester Cycloartenol and cycloartenol obtained in Examples 62 to 64 above Branol or 24-methylenecycloartanol-
41.7 of 3-methoxy-4-nitrocinnamic acid ester
The title compound was obtained in the same manner as in Example 55 using 0.066 mol of each of g, 42.6 g, and 42.6 g. Yield (%), melting point (℃), specific optical rotation ([
α)'fl(C1,OO,CICl3)) was as follows.

Examples 68-70 Preparation of cycloartenol, cyclobranol or 24-methylenecycloartanol-2-ethoxy-5-nitrocinnamic acid 2-ethoxy-5-4-nitrocinnamic acid 19.5 g (0,
082%le) and 'i') Rofurf) -71z25.
The title compound was obtained by the same operation as in Example 58, except that 0.059 mol of each of 0 g, 26.0 g of cyclobranol, and 26.0 g of 24-methylenecycloartanol were used. These yield (%), melting point ("C) and specific optical rotation ([α)", W (C1,0O1CHC13"
) ) was as follows.

Male side 71 to 73 Cycloartenol, cyclobranol or 24-methylene Cycloartenol, cyclobranol or 24-methylene obtained in Examples 68 to 70 of the method for producing cycloartanol-5-amino-2-nitoxycinnamate ester Cycloartanol-2-
36.2 g of ethoxy-5-nitrocinnamic acid ester
, 37.0 g, or 37.0 g, respectively, in the same manner as in Example 59, to obtain the title compound. These yield (%), melting point (℃), specific optical rotation ([α]
Suga (C1,00, CHCl3) was as follows.

Examples 74-76 Preparation of cycloartenol, cyclobranol or 24=methylenecycloartanol-3-methoxy-4-nitro-α-methylcinnamic acid ester 3-methoxy-4-nitro-α-methylcinnamic acid 17.
3 g (0,073 mol) and cycloartenol 25.
The title compound was obtained by the same operation as in Example 54, except that 0.059 mol of each of 0 g, 26.0 g of cyclobranol, and 26.0 g of 24-methylenecycloartanol were used. Their yield (%), melting point (t'') and specific optical rotation ((Q') V (C1,0O1CIC13)
) were as follows.

Examples 77 to 79 Cycloartenol, cyclobranol or 24-methylenecycloartanol-4-amino-3-methoxy-α-methylcinnamic acid ester Cycloartenol and cyclobranol obtained in Examples 74 to 76 or 24-methylenecycloartanol-3-
0.06 each of 43.6g, 44.5g or 44.5g of methoxy-4-nitro-α-methylcinnamate
By the same operation as Example 55 except that 6 mol was used,
The indicated target compound was obtained. These yields (%), melting points (
°C), specific rotation ([α] tube (C1, OO, CHCl3)
) were as follows.

Examples 80-82 Preparation of cycloartenol, cyclobranol or 24-methylenecycloartanol-5-nitro-2-propoxy-α-methylcinnamic acid ester 5-nitro-2-propoxy-α-methylcinnamic acid 21
．． 2g (0,080 mol) and cycloartenol 25
．． The title compound was obtained by the same operation as in Example 58, except that 0.059 mol of each of 0 g, 26.0 g of cyclobranol, or 26.0 g of 24-methylenecycloartanol was used. These yields (%), melting points ('C) and specific optical rotations ([α) V (C1,00, CICl3
)) was as follows.

Examples 83 to 85 Cycloartenol, cyclobranol or 24-methylenecycloartanol-5-amino-2-propoxy-α-methylcinnamic acid ester Cycloartenol and cyclobranol obtained in Examples 80 to 82 or 24-methylenecycloartanol-5-
0.0 each of 37.7g, 38.5g or 38.5g of nitro-2-propoxy-α-methylcinnamate ester
The title compound was obtained by the same operation as in Example 59 except that 56 mol was used. These yields (%), melting points (℃), specific optical rotations ([α] tubes (C1,00, CHCl3
) ) was as follows.

Examples 86-87 Preparation of cycloartenol or cyclobranol-3-methoxy-4-nitro-α-iso-propylcinnamic acid ester 3-methoxy-4-nitro-α-i 5o-7”ropylcinnamic acid 19. 1g (
The title compound was obtained by the same operation as in Example 54, except that 0.059 mol of each of 0.072 mol) and 25.0 g of cycloartenol or 26.0 g of cyclobranol were used. The yield (%), melting point ('C), and specific optical rotation ([α] tube (C1,00, CICl3>) of these were as follows.

Examples 88 to 89 Preparation of cycloartenol or cyclobranol-4-amino-3-methoxy-α-1ao-propylcinnamic acid ester Cycloartenol or cyclobranol-3-methoxy obtained in Examples 86 to 87 -4-nitro-α-iso-propylcinnamic acid ester of 44.5 g, 45.4 g or 45.4 g of each 0.
The title compound was obtained by the same operation as in Example 55, except that 0.066 mol was used.

These yield (%), melting point (℃), specific optical rotation ((α)
W(C1,0O1CICI3)) was as follows.

Examples 90-92 Preparation of cycloartenol, cyclobranol or 24-methylenecycloartanol-p-nitro-α-methylcinnamic acid ester p-nitro-α-methylcinnamic acid 78.3 g (0,
378 mol) to thionyl chloride 112d (4.0 equivalents)
and dimethylformamide lte were added thereto, and the mixture was stirred at 60°C for 2 hours. After concentrating the reaction solution under reduced pressure, dioxane 250-
and 250 ml of pyridine, followed by 125.0 g of cycloartenol, 129.1 g of cyclobranol, or 129.1 g of 24-methylenecycloartanol.
．． 293 mol was added and stirred at 60°C for 2 hours. After the reaction was completed, the solvent was distilled off under reduced pressure, and the resulting residue was extracted with chloroform. The chloroform layer was washed with water and then with saturated aqueous sodium bicarbonate, dried, and concentrated under reduced pressure. The residue was recrystallized from chloroform-ethanol (1:3) to obtain the desired compounds. The yield (%), melting point (°C), and specific optical rotation ([α] tube (C1,0O1CI (C13)) of these were as follows.

Fruit mfi193-95 cycloartenol, cyclobranol or 24-methylenecycloartanol-p
-Production method of amino-α-methylcinnamic acid ester Cycloartenol, cyclobranol or 24-methylenecycloartanol-p- obtained in Examples 90 to 92
16.6 g of nitro-α-methylcinnamic acid ester,
17.0 g or 0.027 mol of each of 17.0 g to 1 acetic acid
Suspend in a mixture of 50- and dioxane 150-, add 9.5 m of 6N-hydrochloric acid-dioxane and 8 g of zinc powder,
After the reaction was completed by stirring at 40° C. for 3 hours, the zinc dust was filtered off, the filtrate was concentrated under reduced pressure, and the resulting residue was extracted with chloroform. The chloroform layer was washed with water and then with saturated aqueous sodium bicarbonate, dried, and concentrated, and the residue was recrystallized from chloroform-ethanol (1:3) to obtain the title compounds. These yields (%), melting points (℃), specific optical rotations ([α
] tube (C1,00,ClCl5)) was as follows.

(Left below) Examples 96-98 Process for producing cycloartenol, cyclobranol or 24-methylenecycloartanol-m-nitro-α-methylcinnamic acid ester m-nitro-α-methylcinnamic acid 80.4 g (0,
388 mol) to 60 ml of thionyl chloride! (2.1 equivalents) and dimethylformamide 1- were added, and the mixture was stirred at 60°C for 2 hours. After concentrating the reaction solution under reduced pressure, 300 d of dioxane and 200 d of pyridine were added, followed by 1 d of cycloartenol.
25.9g, cyclobranol 130.0g or 24
- 0.2 each of 130.0 g of methylenecycloartanol
95 mol was added and stirred at 60°C for 2 hours. After the reaction was completed, the mixture was concentrated under reduced pressure, and the resulting residue was extracted with chloroform. After washing the chloroform layer with water and then with saturated sodium bicarbonate solution,
Dry, concentrate under reduced pressure, and dissolve the residue in chloroform-ethanol (
1:4) to obtain the desired compounds. These yield (%), melting point (℃), specific optical rotation ([α)
V(C1,0O1CHC13)) was as follows.

Examples 99 to 101 Cycloartenol, cyclobranol or 24-methyleneProduction of cycloartanol-m-amino-α-methylcinnamic acid ester Cycloartenol, cyclobranol or 24-methylene obtained in Examples 96 to 98 Cycloartanol-m-
16.6 g of nitro-α-methylcinnamic acid ester,
17.0 g or 0.027 mol of each of 17.0 g to 1 acetic acid
50- and tetrahydrofuran, and 6N-hydrochloric acid-dioxane 12.5- and zinc powder 1-1 were suspended therein.
6.5 g was added and stirred at 20°C for 2 hours. After the reaction was completed, the zinc dust was filtered off, the filtrate was concentrated under reduced pressure, and the resulting residue was extracted with chloroform. The chloroform layer was washed with water and then with saturated aqueous sodium bicarbonate, dried, and concentrated, and the residue was recrystallized from chloroform-ethanol (1:2) to obtain the desired compounds.

The yield (%), melting point (°C), and specific optical rotation ([α] (C1,0O1C)IC13) of these were as follows.

(Left below) Examples 102 to 103 Process for producing cycloartenol or cyclobranol-p-nitro-α-ethylcinnamic acid ester p-nitro-α-ethylcinnamic acid 8.9 g (0.04
0 mol) dioxane 30me, thionyl chloride 6me (
2.0 equivalents) and 0.1-dimethylformamide,
The mixture was stirred at 60°C for 2 hours. After concentrating the reaction solution under reduced pressure, 30-dioxane and 20-pyridine were added, followed by 0.030 mol each of 12.8 g of cycloartenol or 13.2 g of cyclobranol, and the mixture was stirred at 60° C. for 2 hours.

After the reaction, the mixture was concentrated under reduced pressure, and the resulting residue was extracted with chloroform. The chloroform layer was washed with water and then with saturated aqueous sodium bicarbonate, dried, and concentrated under reduced pressure. The residue was recrystallized from chloroform-ethanol (1:3) to obtain the desired compounds. These yields (%), melting point (℃), specific optical rotation (
[α) W (C1,0O1CHC13) ) was as follows.

Examples 104-105 Preparation of cycloartenol or cyclobranol-p-amino-α-ethylcinnamate ester Preparation of cycloartenol or cyclobranol-p-nitro-α-ethylcinnamate obtained in Examples 102-103 0.027 mol of each of 17.0 g or 17.4 g was suspended in a mixture of 150 g of acetic acid and 200 g of tetrahydrofuran, and 12.5 ml of 6N-hydrochloric acid-dioxane was added thereto.
and 16.5 g of zinc powder were added thereto, and the mixture was stirred at 22°C for 2 hours.

After the reaction, the zinc dust was filtered off, the filtrate was concentrated under reduced pressure, and the resulting residue was extracted with chloroform. chloroform layer with water,
Subsequently, it was washed with saturated sodium bicarbonate solution, dried, and concentrated under reduced pressure, and the residue was recrystallized from chloroform-ethanol (1:3).
The indicated target compounds were obtained. These yields (%)
, melting point (℃), specific optical rotation ([α) 9 (C1,0O1
CHC13)) was as follows.

'lJi Example 106 Preparation of 24-methylenecycloartanol-3-methoxy-4-nitrobenzoic acid ester 24-methylenecycloartanol 93.0g (0,
93.7 g of 24-methylenecycloartanol-3-methoxy-4-nitrobenzoic acid ester was obtained by the same procedure as in Example 56, except that 211 mol) was used.

Yield 71.6%, melting point 205-206℃ Specific rotation [α]
Suga・S+56.5° (C1,00, CHCl3) Elemental analysis result C70HP7N O5 (as molecular weight 619.85) Calculated value (%'): C75,57H9,27N 2
．． 26 Actual value (%): C75.5L H9.3
8N 2.2850% Example 107 Preparation of 24-methylenecycloartanol-4-amino-3-methoxybenzoic acid ester 24-methylenecycloartanol-3-methoxy-4-nitro obtained by the method of Example 106 24-methylenecycloartanol-4-amino-3-methoxybenzoic acid ester 6 was prepared using the same procedure as in Example 57, except that 92.2 g (0,149 mol) of benzoic acid ester was used.
2.8g was obtained.

Yield 71.5%, melting point 222-223℃ Specific rotation [α]
Suga +63.2° (C1,00, CHCl3) Elemental analysis result 037 HF9 N O3 (molecular weight 589.
86) Calculated value (%): C79,41H10,08N 2
．． 37 Actual value (%): C79,38H10,14
N 2.35 Example 108 Cycloartenol-4
-Production method of amino-3-methoxybenzoic acid ester 4-acetamido-3-methoxybenzoic acid 6.5g (0,
031 mol) was dissolved in dioxane 110-.

This solution was stirred at 20°C and 21.
Add 0- and then add 0.5-pyridine at 50°C.
The mixture was allowed to react for 5 minutes. After concentrating the reaction solution under reduced pressure to remove thionyl chloride, 10.0 g of cycloartenol (0,023
mol) was added at 20° C., and 20 ml of pyridine was further added. After reacting this at 70°C for 3 hours, the solvent was distilled off under reduced pressure, and the resulting residue was dissolved in 100% chloroform and washed with saturated aqueous sodium bicarbonate. Furthermore, the saturated sodium bicarbonate solution was extracted five times with 100 ml of chloroform. The chloroform layers were combined and dried, concentrated under reduced pressure, and then subjected to silica gel column chromatography [solvent chloroform-ethyl acetate, (1:
6) Dichloroflutenol-4-acetamido-3-methoxybenzoic acid ester 1 was obtained by purification according to ).
0.8g was obtained.

Yield 76.5%, melting point 224-225℃ Specific rotation [α]
Tube +61.5° (ci, oo, CICl3) To 10.0 g (0,016 mol) of the cycloartenol-4-acetamido-3-methoxybenzoic acid ester obtained above, add 200 w1 of tetrahydrofuran and 20% of 30% hydrochloric acid.
After the reaction was completed, the solvent was distilled off under reduced pressure, dissolved in 300 w1 of chloroform, and the chloroform layer was washed with 200 w1 of IN caustic soda water and then with saturated brine. Extracted with chloroform three times. The chloroform layers were combined, dried and concentrated under reduced pressure.
Purification by silica gel column chromatography [solvent: ethyl acetate-hexane, (1:6)] gave 5.4 g of cycloartenol-4-amino-3-methoxybenzoate.

Yield 58.7%, melting point 186-187℃ Specific rotation [α]
Tube +64.4° (C1,00, CHCl3) Example 109 Preparation of cyclobranol-4-amino-3-methoxy-α-methylcinnamic acid 4-acetamido-3-methoxy-α-methylcinnamic acid 2
1.93g (0,088mol) of dioxane 150-
To this, add 25.7-thionyl chloride to make 60
The mixture was heated and stirred at ℃ for 2 hours. After the reaction was completed, the solvent was distilled off under reduced pressure. This residue was dissolved again in 15M dioxane and then in 50M pyridine, and to this was added 30M cyclobranol.
g (0.06 B mol) was added and stirred at 60° C. for 2 hours. After the reaction is completed, the solvent is concentrated under reduced pressure and the residue is ethyl acetate (300111!). was added, and the precipitated crystals were collected by filtration. Cyclobranol-4-acetamide-3- was purified by purifying the crystals by silica gel column chromatography [solvent chloroform-ethyl acetate, (1:6)].
38.5 g of methoxy-α-methylcinnamic acid ester was obtained.

Yield 84.2%, melting point 248-249℃ Specific rotation [α]
Suga +38.2° < c i, oo, CBCl3)
34.4 g (0,05
1 mol) in 300% of tetrahydrofuran.
0% hydrochloric acid 60111 was added and stirred at 70°C for 2 hours.

After the reaction, the solvent was distilled off under reduced pressure, and the residue was purified twice by silica gel chromatography [solvent: chloroform-ethyl acetate, (1:6)] to give cyclobranol-4-amino-3-methoxy-α-methylcinnamate. 18.9 g of acid ester was obtained.

Yield 58.8%, melting point 225-226℃ Specific rotation [α]
Tube +42.0° (C1,00, CHCl3) Example 110 Preparation of 24-methylenecycloartanol-4-amino-3-methoxycinnamic acid ester In the method of Example 109, 4-acetamido-3-methoxy-α- Same except that 21.93 g (0,088 mol) of 4-propioamide-3-methoxycinnamic acid was used instead of methylcinnamic acid, and 30 g (0,068 mol) of 24-methylenecycloalknol was used instead of cyclobranol. 38.4 g of 24-methylenecycloartanol-4-propioamide-3-methoxybenzoic acid ester was obtained by the operating method.

Yield 83.8%, melting point 210-211℃ Specific rotation [α]
Suga +39.4° (C1,0O1CIC13) Also, cyclobranol-4-acetamido-3-methoxy-α-
Except that 35.2 g (0,052 mol) of 24-methylenecycloartanol-4-propioamido-3-methoxycinnamic acid ester was used instead of methylcinnamic acid.
By the same procedure as in Example 109, 18.7 g of 24-methylenecycloartanol-4-amino-3-methoxycinnamic acid ester was obtained.

Claims (1)

[Scope of Claims] 1. an α-alkylcinnamic acid ester having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms and a nitro group, which has a triterpene alcohol monosubstituent or disubstituent group attached to a benzene nucleus; A benzoic acid or cinnamic acid ester having a disubstituted group of an alkoxy group having 1 to 4 carbon atoms and an amino group, or an alkoxy group having 1 to 4 carbon atoms and an acylamino group having 2 to 5 carbon atoms, to a benzene nucleus. 2. The triterpene alcohol is cycloartenol, cyclobranol, 24-methylenecycloartanol,
lanosterol, lanosterol, agnosterol,
Cyclosadol, dihydroagnosterol, cyclolaudenol, cycloartanol, cycloeucalenol, Uhol, butyrospermol, circalol,
The organic acid ester according to claim 1, which is euphorbol or damaradienol. 3. Claim 1 in which one substituent is an amino group, a nitro group, a hydroxy group, an alkoxy group having 1 to 4 carbon atoms, an acylamino group having 2 to 5 carbon atoms, or an alkylcarboxy group having 2 to 6 carbon atoms α-carbon number 1 to 4 as described in item or item 2
Alkyl cinnamic acid ester. 4. The disubstituted groups are a hydroxy group and an alkylcarboxy group having 1 to 4 carbon atoms, a hydroxy group and an alkylcarboxy group having 2 to 6 carbon atoms, an alkoxy group having 1 to 4 carbon atoms and an alkylcarboxy group having 2 to 6 carbon atoms, An alkoxy group having 1 to 4 carbon atoms and a nitro group, an alkoxy group having 1 to 4 carbon atoms and an amino group, an alkoxy group having 1 to 4 carbon atoms and an acylamino group having 2 to 5 carbon atoms, an alkoxy group having 1 to 4 carbon atoms 2 pieces, carbon number 2-6
The α-alkyl cinnamic acid ester having 1 to 4 carbon atoms according to claim 1 or 2, which has two alkylcarboxy groups or two hydroxy groups. 5, 3-methoxy-4-nitrocinnamic acid of cycloartenol or cyclobranol; 4-amino-3-methoxycinnamic acid; 2-nitoxy-5-nitrocinnamic acid; 5-amino-2-nitoxycinnamic acid; 3-methoxy -4-nitrobenzoic acid; 4-amino-3-methoxybenzoic acid; 2-methoxy-5-nitrobenzoic acid or an ester of 5-amino-2-methoxybenzoic acid; acid ester. 3-methoxy-4-nitrocinnamic acid of 6,24-methylenecycloartanol; 4-amino-3-methoxycinnamic acid; 2-nitoxy-5-nitrocinnamic acid; 5-amino-2-nitoxycinnamic acid; 3-methoxy- The organic acid ester according to claim 1, which is an ester of 4-nitrobenzoic acid or 4-amino-3-methoxybenzoic acid. 7. m- or p-nitro-α-methylcinnamic acid of cycloartenol or cyclobranol; m- or p-amino-α-methylcinnamic acid; 3- or 4-propionyloxy-α-methylcinnamic acid; 3- or 4-Hydroxy-α-methylcinnamic acid; 3- or 4-butyryloxy-α-ethylcinnamic acid; 3- or 4-hydroxy-α-ethylcinnamic acid; 2-hydroxy-α-methylcinnamic acid; p-nitro-α-ethylcinnamic acid or the α-alkylcinnamic acid ester having 1 to 4 carbon atoms according to claim 3, which is an ester of p-amino-α-ethylcinnamic acid. m- or p-nitro-α-methylcinnamic acid of 8,24-methylenecycloartanol; m- or p
-Amino-α-methylcinnamic acid; 3- or 4-propionyloxy-α-methylcinnamic acid; 3- or 4-hydroxy-α-methylcinnamic acid; 3-butyryloxy-α-ethylcinnamic acid or 3-hydroxy-α-ethylcinnamic acid An α-alkyl cinnamic acid ester having 1 to 4 carbon atoms according to claim 3. 9. 3-methoxy-4-propionyloxy-α-methylcinnamic acid of cycloartenol or cyclobranol; 4-hydroxy-3-methoxy-α-methylcinnamic acid; 4-butyryloxy-3-methoxy-α-ethylcinnamic acid: 4-hydroxy-3-methoxy-α-ethylcinnamic acid; 4-hydroxy-3-methoxy-α-butylcinnamic acid; 3-nitoxy-4-hydroxy-α-methylcinnamic acid; 3-nitoxy-4-hydroxy-α-propyl cinnamic acid; 3-methoxy-4-nitro-α-methylcinnamic acid; 4-amino-3-methoxy-α-methylcinnamic acid; 5-nitro-2-propoxy-α-methylcinnamic acid; 5-amino-2-propoxy- α-Methylcinnamic acid; α according to claim 4, which is an ester of 3-methoxy-4-nitro-α-iso-propylcinnamic acid or 4-amino-3-methoxy-α-iso-propylcinnamic acid. - Alkylcinnamic acid ester having 1 to 4 carbon atoms. 10,24-methylenecycloartanol 3-methoxy-4-propionyloxy-α-methylcinnamic acid; 4-hydroxy-3-methoxy-α-methylcinnamic acid; 4-butyryloxy-3-methoxy-α-ethylcinnamic acid; 4 -Hydroxy-3-methoxy-α-ethylcinnamic acid: 4-hydroxy-3-methoxy-α-butylcinnamic acid; 3-ethoxy-4-hydroxy-α-methylcinnamic acid; 4-hydroxy-3-propoxy-α-propylcinnamic acid Acid; 3-methoxy-4-nitro-α-methylcinnamic acid; 4-amino-3-methoxy-α-methylcinnamic acid; 5-nitro-2-propoxy-α-methylcinnamic acid or 5-amino-2-propoxy-α -α1 carbon number 1 according to claim 4, which is an ester of methylcinnamic acid
~4 alkylcinnamic acid esters. 11. Cycloartenol 3-methoxy-4-propionyloxycinnamic acid; 3-methoxy-4-valeryloxy-α-propylcinnamic acid; 4-hydroxy-3-methoxy-α-propylcinnamic acid; 4-capryloxy- 3-methoxy-α-butylcinnamic acid; 3-ethoxy-4-hydroxy-α-ethylcinnamic acid; 3-ethoxy-4-hydroxy-α-butylcinnamic acid; 4-hydroxy-3-propoxy-α-methylcinnamic acid or 4- The organic acid ester according to claim 4, which is an ester of hydroxy-3-butoxy-α-methylcinnamic acid. 12. The organic acid ester according to claim 4, which is cyclobranol-4-hydroxy-3-propoxy-α-ethylcinnamic acid ester. 13, an α-alkylcinnamic acid having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms and a nitro group, which has a triterpene alcohol and one or two substituents attached to the benzene nucleus;
Alkoxy group with 1 to 4 carbon atoms and amino group or 1 to 4 carbon atoms
1. A method for producing a triterpene alcohol organic acid ester, which comprises reacting an acid halide of benzoic acid or cinnamic acid in which a disubstituted group of an alkoxy group of 4 and an acylamino group having 2 to 5 carbon atoms is bonded to a benzene nucleus. 14. The triterpene alcohol is cycloartenol,
Cyclobranol, 24-methylenecycloartanol, lanosterol, lanosterol, agnosterol, cyclosadol, dihydroagnosterol, cyclolaudenol, cycloartanol, cycloeucalenol, uhol, butyrospermol, circalol, eupholbol or damas 14. The method for producing an organic acid ester according to claim 13, which is radienol. 15. The acid halide of the organic acid has a nitro group and 2 or more carbon atoms.
A patent which is an acid halide of α-alkylcinnamic acid having 1 to 4 carbon atoms, in which one substituent of an acylamino group of 5, an alkoxy group having 1 to 4 carbon atoms, or an alkylcarboxy group having 2 to 6 carbon atoms is bonded to a benzene nucleus. A method for producing an organic acid ester according to claim 13 or 14. 16. The acid halide of organic acid is an alkoxy group having 1 to 4 carbon atoms and a nitro group; an alkoxy group having 1 to 4 carbon atoms and an acylamino group having 2 to 5 carbon atoms; an alkoxy group having 1 to 4 carbon atoms and/or a carbon The organic acid ester according to claim 13 or 14, which is an acid halide of α-alkylcinnamic acid having 1 to 4 carbon atoms, in which a disubstituted group of 2 to 6 alkyl carboxy groups is bonded to a benzene nucleus. manufacturing method. 17. Cinnamic acid or cinnamic acid in which the acid halide of the organic acid has disubstituted groups of an alkoxy group having 1 to 4 carbon atoms and a nitro group, or an alkoxy group having 1 to 4 carbon atoms and an acylamino group having 2 to 5 carbon atoms, to a benzene nucleus; 15. The method for producing an organic acid ester according to claim 13 or 14, which is an acid halide of benzoic acid. 18, acylamino group having 2 to 5 carbon atoms or 2 to 6 carbon atoms
One substituent for an alkylcarboxy group; an alkoxy group having 1 to 4 carbon atoms and an alkylcarboxy group having 2 to 6 carbon atoms; a disubstituent for an alkoxy group having 1 to 4 carbon atoms and an acylamino group having 2 to 5 carbon atoms; or α-C1-C4 having a disubstituent of an alkylcarboxy group having C2-C6 attached to a benzene nucleus
A monosubstituent of a hydroxy group or an amino group characterized by being deacylated from a triterpene alcohol ester of an alkylcinnamic acid; A method for producing a triterpene alcohol ester of α-alkylcinnamic acid having 1 to 4 carbon atoms, in which a disubstituted group or a disubstituted hydroxy group is bonded to a benzene nucleus. 19. A carbon number characterized by deacylation from a triterpene alcohol ester of cinnamic acid or benzoic acid in which a disubstituted group of an alkoxy group having 1 to 4 carbon atoms and an acylamino group having 2 to 5 carbon atoms is bonded to a benzene nucleus. A method for producing a triterpene alcohol ester of cinnamic acid or benzoic acid in which 1 to 4 disubstituents of an alkoxy group and an amino group are bonded to a benzene nucleus. 20, one substituent of nitro group or nitro group and carbon number 1 to 4
α-, which has a disubstituted alkoxy group of
A triterpene alcohol ester of an alkylcinnamic acid having 1 to 4 carbon atoms is reduced with a metal and an acid. A monosubstituent of an amino group or a disubstituent of an amino group and an alkoxy group having 1 to 4 carbon atoms is added to a benzene nucleus. α-carbon number 1 bonded to
-4 Method for producing triterpene alcohol ester of alkylcinnamic acid. 21. Amino group and carbon number 1 characterized by reducing triterpene alcohol ester of cinnamic acid or benzoic acid, which has a disubstituted group of a nitro group and an alkoxy group having 1 to 4 carbon atoms attached to a benzene nucleus, with a metal and an acid. A method for producing a triterpene alcohol ester of cinnamic acid or benzoic acid in which a benzene nucleus has a disubstituted alkoxy group of -4. 22. The triterpene alcohol is cycloartenol,
Cyclobranol, 24-methylenecycloartanol, lanosterol, lanosterol, agnosterol, cyclosadol, dihydroagnosterol, cyclolaudenol, cycloartanol, cycloeucalenol, uhol, butyrospermol, circalol, eupholbol or damas The manufacturing method according to claim 18, 19, 20 or 21, wherein the radienol is radienol.