JPS5843998A - Novel steroids - Google Patents

Abstract

PURPOSE:A compound shown by the formulaI(one of R1 and R2 is H and the other is OH or both form oxo group) or shown by the formula II[Z is double bond, a group shown by the formula III (R is H or acetyl), Z' is a group shown by the formula IV]. EXAMPLE:3alpha,5-Cyclo-5alpha-stigmasta-22-ene-6-ol. USE:An intermediate for preparing a plant growth regulator. PROCESS:For example, a stigmasterol shown by the formula V (R is H) is tosylated, and hydrolyzed to give i-stigmasterol. This compound is oxidized with Jones chromic acid, heated in sulfolane containing p-toluenesulfonic acid, oxidized catalytically with osmium tetroxide or acetylated after the catalytic oxidation, to give a compound shown by the formulaIor a compound shown by the formula II.

Description

[Detailed description of the invention] ・This is a new compound that has not been described in any literature.

c In formula R1 and R2 #i one represents a hydrogen atom and the other represents a hydroxyl group, or both represent an oxo group] 77/ /'/'/',/'' 7/ represents a direct bond or U, R 2α, 3α, which has a hydrogen atom or declination, has a plant length AmtIp and is represented by the formula 1, which is useful as a plant growth purifier.

22.23-Tetra of Sea 24S-Ethyl B
One E-7-off-"j-5α-cholestan-6-one (hereinafter referred to as [hon-shichiprasinola"id]) and its tetradoceol form (2α, 3α).

22.23-, Tet, U Ft Tetler 245-English Rue B one bottle t-7-O115α-Koshi Stan-61 Oshi,
It is useful as an intermediate for the production of [hereinafter referred to as "ho-7-brassinolide P acetate"].

[In the formula, R represents a hydrogen atom or L&. The production of the above-mentioned H-7-prasinolide and the present L-prasinolide acetate from the Steroid gradient of the present invention will be described in detail in Reference Examples below.The method for producing the Steroid gradient of the present invention will be described below. For example, as shown in the reaction equation below, the present invention can be applied to Stigmaster 0-L (Stakemaster 5.22
-Dien-3-O”, CJ9HQ80, Molecule Eater 41
2.67) as a starting material, for example as described in the literature (J, A4t, Ckzwi, Sp et al.

62.2006 (1940)).

Reaction equation> (1) R=H (stigma stereo) (■)
R = rs In the above reaction scheme, the tosylate represented by the formula (-) is produced by tosylation of the stigma sterol represented by the formula (■), and the tosylate represented by the formula (ff) is generated by the s4 medium decomposition of the tosylate. The reaction for producing j-stigma sterol is described in 10 documents (J, Org.

It can be easily carried out according to the method described in C.Kllllg., 28.571 (1963). l obtained by the above
- Ketone (V) from stigma star 0- (W) -
The formation is carried out, for example, by an oxidation reaction using Jones' chromium #. This oxidation reaction easily proceeds under conditions F that are almost the same as those of the known oxidation reaction using di-3-cysic acid. For example, toluenesulfone
ketone (V) in sulfolane containing 160'C
It is carried out by heating at #* for about 70 minutes. This heating reaction proceeds in the same way even if ordinary polar solvents such as pyridine are used in addition to the above-mentioned streaky run, and the reaction is carried out in an inert gas atmosphere such as Alj:J. It is preferable to use the steoid@([6
) is obtained. A compound of the present invention in which Z and Z in the general formula (1) are other than = direct bond (l-ri is the above-mentioned ST0i, dom (i is then
It can be obtained by catalytically oxidizing osmium tetroxide (OzO'4) or the like, or by subsequent a7tylation. The above-mentioned contacting can be carried out by utilizing an assimilation reaction using ordinary 0t04, but according to the research of the present inventors, in particular, as a catalyzing agent, Ox Q a and N-methyl When using T-fluorin-M-O+Cyto in combination, the double bond of the raw material compound 1T, which has a very small amount of wax compared to the 4 arguments of O x Oa normally required for this Haji reaction.
It has been found that the process can be easily carried out by using OsO4 at a concentration of about /2°7 to L. The above reaction is advantageously carried out in a conventional aqueous tetrahydrofuran solvent under an inert gas atmosphere such as Plt, J or the like. In this way, the tetraol of the present invention having the above formula (in which R is a hydrogen atom) can be obtained.

I: Tetraol? The cetylation reaction can be carried out according to a conventional method using acetic anhydride.) The preferable P-cetylation reaction is carried out using, for example, acetic anhydride-pyridine-dimethyl-P-minobiridine. The details are as shown in the examples below.Thus, the above formula CI-
b) Obtaining the tetra-Pt metal of the present invention in which the middle R is P settt. may be possible, but l1li
The product is usually carried out by a single suitable means, such as a solvent extraction method, a recrystallization method, a 4-method, a galamic acid filtrate, a 1ll-ri filtrate, and the like.

According to the present invention, easily available stigmasterol (1) is used as a starting material to easily produce a desired metal object in a short time without going through any complicated operations or processes that require a long period of time. You can earn at a rate. Moreover, from the stem tilt of the present invention, plants can be grown efficiently with just 4 easy operations.
The present t-prasinolide and homoprasinolide Pt-tate, which are useful as adjuvants, can be produced, and in this respect, the present invention is extremely useful.

Hereinafter, an example of manufacturing the compound of the present invention will be shown.

1) Stakemastyryl tosylate [Compound (0)]
Manufacture power
Dry stigmatizer 15 according to page 1 (1963)
．． 18. Toluene chloride was recrystallized from petroleum ether (boiling point 60-70°C) in a solution of 200 ml of dry lysine. After leaving the reaction mixture in the dark overnight, it was poured into a water-cooled 5% straight carbon potassium aqueous solution. It is recrystallized from seven tons of dried P to obtain colorless crystalline Stake Mastyril with a temperature of 147-148°C.
= -49゜2) Preparation of i-stigmastyryl tosylate obtained in 1) above 5. O
f and Charcoal Potassium 3.22 to Pt! ) Pour the solution containing 21K and 200Id of water over 6R to make the total dk700.
Cover with dKa, dilute with water, and extract with ether. Aete L-
After washing with water, drying with potassium carbonate, and evaporating to dryness under reduced pressure, a colorless oil 3.9I was obtained.
arixil) 15 (Pour it into a column of NF and pass 250 d of petroleum ether-benpine (2:3) fi liquid to obtain colorless oily I-stigma sterol 3.01, P
t) - Crystallization from aqueous solution A to obtain colorless crystals with a melting point of 48-50°C.

Water? Samples for analysis after recrystallization from Nanatoshi go to ＼24
5-ethyl-3α, 5-sic0-5α-cholesto-22
-Synthetic i-stigmaste 0-L (3α, 5-Schiff 0-5α-
Stakemaster 22-en-6-all)6. Of? Add 8N of di-3-i (JInex) to a water-cooled stirring F in a solution of 100s of setone and #I, *(CrO
2) After stirring for 5 minutes, add a small amount of methanol and decompose the monic acid with one swig. D-Remove the sample to reduced pressure F in a tally evaporator. J! Ja
was dissolved in a water-r-chill mixture, and the ether layer was washed with water, an aqueous sodium bicarbonate solution, and saturated brine in that order, and the ether layer was washed with sulfuric acid.
Dry with magnesium, bind after pis, and crystallize from 99% ethanol to obtain acicular crystals of 245-ethyl J1/-3α, 5-cyc0-5α-cholesto-22-nidi, with a melting point of 98-99'C. -6-O:, I4.81F (yield 80%
).

Analytical grade after recrystallization from ethanol has a melting point of 10
2-103℃, [α), = +19.5 CC = s, o
The IR, NMR and elemental analysis results are shown below.

2 beak ax (s: 11-le) = 1885 (j), 1310 (beak), 1300 (f), 1250 (w >, 1220 (-, ), 1200 (= ), 117L) (m
), l150cm), 1130(-), 1120(#I>, 1075(Zeng), 1055.(tt+), 1040(1
), 1020 (->, 101005 (, 970 (j), 925 (tone), 920 (-), 895 (*), 870 (-), 840 (-), 810 (W), 780 (*), 720(f)a11 δ(f, □MHz% CDCl3) =0.73.0.
80.0.86.0.90.

1.02.1.10 (18#, CM3), 1.1-2
．． 7 (26#, CH2, CM) 5-15 C2M
) p door elemental analysis value (as C29Hj16') calculated value (%)
C84,81H11,29 Dormitory side value (%) C85,
41# 11.44-Jen-6-one [Compound (1
-a) Add 180 mg of melted toluene to the production d of ) to create a P-look atmosphere F 16 tJ”
Heat at c for 70 minutes. Pour cold infiltration water, extract with hempin-toluene (1:l) mixture, wash the extract with water, then wash with saturated saline, dry with magnesium sulfate, and concentrate the 1F5 superinfiltrated solution with a rotary evaporator to a reduced pressure of F. .

One residue was also mixed with Merck's silica (Krzzzzlyzl).
6Q, 70-230 mets! zl, 35g%'l -to +
Purify with a mixture of Yen-he + Sun-vecipin (1:l) and purify with
4S-ethyl-5α-cholesta-2,22-diene-6
-one 2.3F (yield 66%) is obtained. This is 99
% ethanol to obtain prismatic crystals with a melting point of 111-112°C.

[α), =+18.4 ((1”=1.151,
CHCg, )ν net, □(nu,;1-ru)=3020(
edge), 1705 (1), 1650 (cao), 1330 (snow), 1310 (-), 1300 (various), 1285 (cao)
, 1260 (sea bream), 1230 (solution), 1190 (fushi),
1180 (replacement), 1160 (-), 1120 (wIl)
, 1100(-), 1070(-), 1045(1-)
, 1020(-3,995(-), 96g<->, 94
0 (嘗), 870 (s-), 845 (-), 815 (W
), 780 (-), 750 (w), 720 (-), 67
0(11g)3-”lj<60MM1.CDCl5)=
0.69.0.78.0.84.0.88.0.96.
1.08 (1B circle Cμ3), i, i~2.5<24M
-CM2, -cit-)%5.10 (2#), 5-69
(2#, br, z) Toto crocodile elemental analysis value (C29'46' and 0.

Calculated value (*) C84,81, M 1-1.29 Actual value (%) C85,19, H11,60.

Manufacturing example 4 2(X, 3α, 22.23-f Torad O'F"
Preparation of 1-245-ethyl-5α-cholestacy-6-oxy[Compound (T-1), R=H] 24S-ethyl-5a obtained according to Preparation Example 3 above
-Colestar-2,22-Gel-6 1 year old 4, change Of to Tetrahyte 0 flage 80s/, and add 0zOu to this
A solution of 11,7 slK of 1-butano-1, 2,10% of N-methyl phosphoric acid, and 20 m of water were added, and the mixture was stirred at room temperature for 2 days under an atmosphere of nitrogen. -Methyl fluorolycyN-o+cytoIf[1111袢t-IElfllll&ff HISTORY KII
After stirring and reacting for 1 day, add 2 g of hydroxide and 4 s of water. Add the solution dissolved in the solution, shake and mix to remove 0sKll of OxOa, pass through the t-light layer, and remove in the furnace. Concentrate the P solution, mix Ri00*lum and dilute hydrochloric acid, dry the Ri00*lum layer with potassium carbonate and concentrate, mix the residue with ether-petroleum ether mixture and leave to stand L7, 2α, 3α , 22.23-tetra-cholesteryl-24S-ethyl-5α-cholesteryl-6-cholesteryl-2.4I (yield 52%) is obtained. This is 99
% ethanol to obtain prismatic crystals.

Melting point 143-148°C (shishiter) 200-210°C (melt) [α)21= 11g'<C=1.294, CMC
l3) νwag (nuj1-jL)=3350(j),
1715(S), 1340(-), 1320(-1),
1310(-), 1280(-), 1250(-),
1240 (#), 1230 (-), 1205 (1-),
1180 (silence).

1150 (W), 1115 (-1), 1100 (solution),
1080 (z), 1065 (1), 1055 (j
), 1050(f), 1035(J), 1oio
< z ), 1000 (-), 990 (clear), 965 (
-), 940 (-), 930 (1-), 900 (W)
, 870 (-), 840 (1,790 (Cao), 780
(-), 750 (police), 720 (-), 700 (w)3
-1 Calculation*(96) C72,76,7/ 10.53w
5 value (%) C73,03,7' 11.17 Production example 5 2αe 3a* 22.23 -tetraacetate 2
1lff of 45-ethyl-5α-cholestasy 6-osi
i 2α, 3α, 22.23-tetra-Fa + C24S-ethyl-5α-Coshistar>-6-f (D 380 'f 't IE f
Illk e! Dissolve the mixture, add 0.11 of acetic anhydride Is/and 4-(N,N',; methyl atri) lysyl, and leave at room temperature overnight.

Pour ice and dilute hydrochloric acid and extract with ether. The ether layer was washed with water, an aqueous sodium bicarbonate solution, and a saturated saline solution in that order, dried over magnesium oxide, and then inverted for 14 minutes.
lltl 60% 70-230J"J!tl, rhinoceros in 10 sashimi) Purify K-teri 0. Bath out with a mixture of N- sashimi and ethyl acetate L (9:l to 4:l) 2a, 3α, 22.23-nato5acetacy245-ethyl5α-cholestacy6-oxy500q
(yield 95%)'. This is an isomer mixture (approximately 1:l) of <22R, 23R) and (225,235)
It exhibits a gum-like appearance.

νwag (film) = 1740 (j), 1705 (j
), 1230(j), 1170(-1), 1150(#
-), 1100 (1-), 1070 (Cao), 1030 (
Solution), 1010 (111) =, 980 (Cao), 965
(*), 940 (嘗), 915(s), 890
(*), 875 ($) cs-1 above <22B, 23R)
The isomer mixture of the t22S, 23S) isomers is separated into each isomer, ie, the (22B
, 23R) and <225°235).

Examples of the production of the present t-prasinolide and the present t-brassinolide atate from the steroids of the present invention are listed below as reference examples.

Reference example l - Homoprasinolide acetate (2α, 3a.

22.23-tetraacetof-24S-ethyl-
B one v knee 7-o thousand su-5α-cholestasy 6-oshi l) l! 598 # of Steoid II (tetraacetate) of the present invention obtained in Preparation Example 5 was dissolved in a dry jig 00 metasi 3'Os/, and 3 g of sodium 3I finely powdered ricic acid-water was added thereto and stirred. Separately 905&i hydrogen peroxide solution 0.5-
was suspended in Jig 00 Metashi 5d, then trifluoroacetic anhydride 3.3- was added and mixed under water cooling to obtain a homogeneous peroxide.
Make a solution. Drop this into the above solution while stirring. When the exothermic reaction is completed, heating and stirring current is applied for 5 hours. After cooling, ice water is added, and the aqueous layer is extracted with a Jig 00 metal filter.The extracted layer and the Jin 00 metal layer are combined, washed with carbonated water, thorium water, and jam, dried over magnesium sulfate, and then concentrated. The residue was purified with silica gel (Mallimtaradl 5slscar tc-
7,20X 1.00g.

～-To 1,000 Sashi medium) and make 0 Mado. R-2α, 3α, 22.23-detraacetate 245-ethyl-B-hoe-1-oxyethyl 5α -Cholestasis 6-O: Obtains 4 os da (yield 66 Biao) (M1
point 174-178°C).

The rod-shaped crystals obtained by recrystallization from an ethyl acetate-petroleum ether mixture have the (22B, 23R) body and <225°235).
It is an approximately 1=1 isomer mixture with a melting point of 176
At ~178℃, [α] is +24.4 (t'=1.00
6% CMCI, > 6% CMCI, the following analysis results are shown.

Incidentally, each of the above isomers can be optically resolved by a conventional method.

νmax (line 1-ru) = 1740 (1), 1720
(1), 1330 (fung), 1315 (-), 1305 (
-), 1250 (1), 1225 (j), 1180
(-), 1170 (resign), 1125 (replacement), 1115 (
III), 1050 (1k), 1040 (solution), 10
15 (#l), 960 (w), 940 (-), 91
5 (1,900 (*).

890 (III), 875 (-), 7et5 (嘗)
,720(w)l'llm-"δ(f)OMMg,cD
ca, )=0.6~1.1 (18#, CM3.0.70
．． 0.79.0.89.0.98), 2.00 (3M,
1), 2.07 (3#, j), 2.10 (6#, j),
3.0 (1#% Crocodile, CHC=0), 4.10 (2#, d
, / = 5 Hz -C# 20-), 4.70~5
．． 50 (4#, -CHoAt, 4.8.5.02.5.
2.5.35)//m elemental analysis value”y;+H5aOx
. ) Calculated value (g6) C67,04, // 8
．． 82 dormitory value (%) C66,93, H8,86 reference @
2 Hotprasinolide (2α, 3ff, 22.23
- Tetra Shido 0,000 Sea 245 - Ethyl B - Ho 7 - 7 -
Production of ↑q-sa-cholestasy 6-osi) In reference example 1 above, 11 acetate 250IIfI was added to tutanol 6.
-, add a water bath solution 1- containing 500 Da of sodium hydroxide, and heat, stir, and reflux for 1 hour.

After stirring at room temperature for an additional hour, 6d of tetrahydroflage was added, and the mixture was acidified with 3 g of 6N-double acid for 1°, followed by heating, stirring, and refluxing for 30 minutes. Distill concentrated IIA (tetrahydride 0) and methanol under reduced pressure, carefully add a small amount of sodium hydrogen envyate to neutralize,
Extract with 0 metasi. After converting the extract with magnesium sulfate, the desiccant was removed and concentrated to obtain 2a, 3α, 22.23.
-Tetrate 0,000 C24S -Ethyl-B-Hot-
7-Oshisu-5α-cholestasy 6-Oshi's 130q (
Yield 709b) is obtained.

Recrystallized from methanol to give a melting point of 186-18B℃, [α
)" = +35.6° ((' = 0.54, CDCI3), a colorless needle crystal is obtained. This Fi is not easily split into light. 22
It is an approximately 1:1 mixture of the R,23B> isomer and the (225,235) isomer, and has the following physical and chemical properties as the isomer mixture, and up to t of this isomer mixture, or each isomer. were separated, and all were found to be useful as plant growth control agents.

νman (nuji x-t) = 3400 (#r, y),
1730 < z A,), 1710(Sk,), 16
95(j), 1405(-1), 1350(-1),
1330(-), 1290(zA), 1280(all
), 12'70 (to 1, ), 1250 (-), 1225
(jL), 11220 (-j), 1190 (#).

1180(m), 1160(tai), 1130(tai), 1
120(#), 11l100(, 1065(f), 10
20(-), 990(all), 965(-), 950
(-), 930 (-), 915 (W), 880 (W),
860 (*), 835 (嘗), 820 (*), 770 (
1-), 715 (rig 1J (60MBl, CDCl5
)=0.6-1.1fifim<188. CM,,0.
70.0.7B, 0.87.0.95), 1.1-2.
5 houses m (22#%CM2, CM), 2.90 houses m (
2#), 3.55 houses - carp (2H), 4- Op p cod (2#, 'br, -CM a O-) 13 (,
NMR (CDCI, CD30D=971) 177.86
Todo tone (C=O) elemental analysis value (as '29#5゜06) calculation * (%)
C70,41,#l(7,199!@*(%)
C70, 71, M 10.29 (or more)

Claims (1)

[Claims] ■ General formula [In the formula, one of R1 and R2 represents a hydrogen atom and the other represents a hydroxyl group, or both represent an oxo group] The relative represents the general formula % formula % [In the formula, ZFi double 2/Fi20ROR double bond or Fi'-J, and R represents a hydrogen atom or a prefix group. ] A steroid characterized by the following. (■ 3α, 5-Shift 0-5α-Stator Master 22
-■ 1 which is C-6-ol, and the steroids according to claim 1. Cl245-XfL-3e1.5-C9O-5Q-
Steroids according to claim 1 comprising colesto-22-nid-6-osyde. (+) 245-ethyl-5α-cholester-2,22-
The steroid according to claim 1/' which is Gel-6. ■ 2α, 3α, 22.2's-Tetra Shido Ot Sea 2
4S-Works Roux 5α-Cholestane-6-One
The steroid inclination described in ° in the first term of the fM calculation range. ■ 2α, 3α, 22.23-tetraacet↑C24
The steroid according to claim 1 which is S-ethyl ILI-5α-cholestane-6-osy