JPS61152665A - Hexa-substituted benzene derivative - Google Patents

Abstract

NEW MATERIAL:The hexa-substituted benzene derivative of formula I (R is alkoxycarbonyl or CH2OH; R<1> and R<2> are alkyl; X is group of formula II-formula IV; R<3> is alkyl). EXAMPLE:3-Chloro-4,6-dimethoxy-5-[( E, E )- 7-(5,5-dimethyl-4-pivaloyloxy-2,5-dihy dro-2-furanyl)-3-methyl-2,6-octadienyl]-2-methylben-zoic acid methyl ester. USE:An intermediate for the production of ascofuranone in high efficiency without using troublesome separation and purification steps. Ascofuranone is expected to be useful as a remedy for adult diseases because of its antiviral activity, carcinostatic activity, blood cholesterol level lowering activity and hypotensive activity and extremely low hepatic toxicity. PREPARATION:The compound of formula I (R is COOR'; X is group of formula II) can be prepared by reacting the compound of formula V (Y is halogen; R' is alkyl) with the compound of formula VI.

Description

Detailed Description of the Invention [Object of the Invention] The present invention relates to the general formula (in the formula, ru is a dicarbonyl group in alkoxy or ha and 7-methyl group in a doro group, ru and t are alkyl groups, and l, X (in the formula ns
is an alkyl group. ). ] The present invention relates to a water-substituted benzene derivative represented by:

[Industrial application field]

The hexasubstituted penzene derivative represented by the general formula (1) of the present invention can be easily converted into an Ascoff 2-non derivative (see the reference side below). Ascon 2 Tsuno is a compound with the structural formula 6.It has antiviral and anticancer properties, has the effect of lowering the amount of cholesterol in the blood, lowering blood pressure, and has extremely low hepatotoxicity. Therefore, it is expected to be a promising drug for adult diseases (see JP-A-48-91278 and JP-A-51-36450).It is also recognized to have an action as a preventive drug for cancer (J, Antibiotics).

Yudan, 1547 (1982)). Particularly in terms of blood pressure lowering effect, it is clear that compounds in which a substituent such as a methyl group is introduced into the hydroxyl group of asconinone are superior (see JP-A-51-36450).

[Conventional technology]

Conventionally, methods for synthesizing ascon-2non include (b) a method of aerobically cultivating ascofuranone-producing bacteria belonging to the genus Ascofuranone (see JP-A-48-9127 No. 3), and (b) a method of total synthesis. (Tetrahedron Lett,
.

Dando, 1547 (1983); Etou, 3795 (198
4)] is known. However, method (ii) has the drawback that the isolation and purification operations for ascon 2non are complicated. In addition, method (b) has the disadvantage that the reaction steps are long and the yield is extremely low.

Therefore, both methods are difficult to adopt industrially.

[Problems solved by the invention]

As a result of the inventors' studies to overcome the drawbacks of conventional methods,
As:r efficiently without going through complicated isolation and purification operations.
The present invention was completed by discovering a water-substituted benzene derivative represented by the general formula (I) that can lead to 7lanone.

[Summary of the invention]

The water-substituted benzene derivative represented by the general formula (1) of the present invention can be produced according to the following reaction formula.

+ (In the formula, Y is) 6 logon atoms, ” , ”, ”
and t is Al I? [First step] In this step, the compound represented by the general formula (II and Ib) is produced by reacting the hakubenzene represented by the general formula (1) with the bromide represented by the general formula (2). The helobenzene represented by the general formula (It) is, for example, 3-bromo-2,4-dihydroxy-6-methylbenzoic acid methyl A/(J, Chem, Soc, Perki
nTrans, 1.1986 (1975)) i/qa
It can be easily obtained by hydrogenation and then hydrogenation in alkali (see reference side below). Examples of helobenzene represented by the general formula (1) include 3-bromo-5-chloro-2,4-dihyde c1-? The two hydroxyl groups of 6-methylbenzoic acid are methyl, ethyl, propyl, ethoxymethyl, methylthiomethyl, 2-(trimethylsilyl)ethyl, (2-methoxy)ethoxymethyl, benzyl, O
- nitrobenzyl, diphenylmethyl group, and methyl-thyl, propyl, t-
Examples include those esterified with a butyl group.

On the other hand, the bromide represented by the general formula (2) is 2°6
-dimeter-8-(tet2hydropin-2-yloxic)-2,6-octagenal (Te-trahed)
ron. (see side).

As the bromide represented by the general formula (2), for example, 5-(7-proso-1,5-dimethyl to but-1,5
-genyl)-2,2-dimethyl-3-? "Varyloxy-2,5-dihydrofucn, (nF in general formula (2)
=t-butyl group) can be used, as well as alkyl group derivatives where t is a methyl group, isopropyl group, etc. can also be used.

Similarly, before alkylating verbenzene represented by the general formula (1), it is preferable to metalize it. Commercially available organic lithium compounds such as butyl lithium, S-butyl lithium, t-butyl lithium, 7-enyl lithium, and methyl lithium can be suitably used as K for metalating helobenzene represented by the general formula (1). More preferably, a copper ate complex is formed by adding organic copper (I) to a thiobenzene derivative or a thiobenzene derivative obtained by reacting with the above-mentioned Lytech 4 compound. As organic steel (I), 1-
Hexycnyl copper (I), 1-pentynyl steel (I), 1-butynyl copper (1) in 3-methyl-3-meth, cyanide steel (I), 7-diluteo M (I), diphenylphos FiI'1l(1), etc. can be mentioned. The amount used for both organic lithium compounds and organic copper compounds is based on the general formula (!
I) represents '44' for benzene, 1.
Use in the range of s mol.

The metalated helobenzene represented by the general formula (1) obtained as described above reacts with the bromide represented by the general formula (2).

When carrying out the reaction, it is desirable to carry out the reaction in a solvent.
For example, nato 2hydrofukun, diethyl ether, 1.2
- Ether solvents such as dimethoxyethane, hydrocarbon solvents such as toluene, samethyl phosphoric acid triamide and N.

Polar solvents such as N-dimethylpropylene flare, N,N,N,N-nato-2methylethylenediamine, or mixed solvents thereof can be used.

The reaction temperature can range from -100°C to the reflux temperature of the solvent.

[Second process]

In this step, the compounds represented by the general formulas (Ia and Ib) are reduced to produce the compounds represented by the general formulas (IC) and (Id).

For example, lithium aluminum hydride,
Tecum borohydride, zinc borohydride, diisobutylaluminum hydride, hydrogenation + trio-1-butoxy ≠ aluminum eculum lithium, bis-(2-methox 7
Conventional hydride reducing agents such as sodium aluminium can be suitably used.

The amount of the reducing agent to be used is usually in the range of 2 to 6 mol for the compound represented by the general formula (Ia and Ib).The reaction is preferably carried out in a solvent.
For example, diethyl ether, tetrahydrofuran, 1.
In addition to ether solvents such as 2-dichloroethane, it is also possible to use solvents that do not react with the hydride reducing agent, such as aromatic solvents such as benzene and toluene, and halogen solvents such as dichloromethane and 1,2-dichloroethane.

The reaction temperature can be selected from a range from -80°C to the reflux temperature of the solvent used.

Hereinafter, the present invention will be explained in detail using Examples and Reference Examples.

Reference Example 1 Methyl A/zooate (1,74 g, 6.7 mmol) was dissolved in ether (30d) in 3-polymer 2,4-dihydroxy-6-methyl, and sul7lyl chloride (0,9
9g, 7.3m-mOl) at room temperature for 4 hours and 30 minutes.

Concentrate under reduced pressure and perform column chromatography (silica gel, dichloromethane-Φsan l:l to 100 21
(eluting with a mixed solvent of ) to obtain methyl 6-methylbenzoate (1.86 g, yield 97 g) as colorless crystals in 3-promo-5-chloro-2,4-dihydride c1: lU3-109℃, IR (KBr): 34g0,1641,1589,14
09°1329.1258,121℃7cm.

NMR (CDCI, ): δ2,59 (s, 3H),
3.97 (s, 3H), 6.49 (br s, IH),
12.19 (s, IH).

+ + M8 (m/z): 298 (M +4.6), 296 (M
+2°+23), 294 (M, 18), 2a6 (25).

264 (100), 262 (78), 183 (11).

63(11).

Total gtq for C,H8BrClO4:C,36,5
8; H, 2,73 chi.

Measurement [: C, 36, 66; H, 2, 72 chi.

3-promo 5-chloro-2,4-dihydro a medium c 6-
Methyl benzoate (0.21 g, 0.69 m Part I)
Dissolve 77 tons (5d) K of dimethyl sulfate (0,24
g, 1,90 mmol and potassium carbonate (0,2
6 g, 1.90 mmol) under reflux conditions for 4 hours and 30 minutes. After diluting with dichloromethane (50ml), the mixture was washed with a mixed aqueous solution of saturated brine (10mg) and water (10ml). After drying and concentrating, it was purified with thin layer Chromadog 2F (silica gel, developing solvent dichloromethane) to give C6 in 3-promo5-rec10-2.4-dift.
-Methyl methyl benzoate (0.21 g, yield 92%) was obtained.

bp: 130°C (bath temperature) 10.09 Torr.

IR(neat):1737.13B7,1259,1
100♂.

NMR (CDCI, ): δ 2.28 (s, 3H
), 3.86 (s, 3H), 3.88 (s, 3H)
, 3.93 (s.

3H).

+ + M8 (m/z): 326 (M +4.13), 324 (
M +2゜+ 51), 322 (M, 40), 295 (21), 29
4 (32), 293 (79), 292 (100), 29
1 (62), 290 (75), 278 (17), 276
(13), 249(17), 247(14), 91(1
5).

Calculated values for C, 1H, 2BrC104: C, 4G,
83; H, 3,74%.

Actual value: C, 4υ, 63; H, 3,87ch.

Reference example 2 0H OCOtBu 2-Methyl-3-butyn-2-ol (2.5 g.

30 mmol) of 'I'HF (150 m) solution, 4 liquids of Putilritek b (1,75 M), 34 m
, 60 mmol) was added at -20°C and stirred for 2 hours.

(E,E)-2゜6-dimethyl-δ-(nato-2hydropyran-2-yl-oxy)-2,6-octagenal (
5,0g, 20mmol) of THF (25I
ILt) #L solution was added at -50°C. The mixture was stirred for 2 hours, heated to room temperature, and ether (5001 tt), saturated brine (50 rj), and water (25 aj) were added. The organic layer was dried and concentrated to give (Ff,E)-12-(tetrahydropyran-2-yl)-2゜6.10-trimethyldodeca-6,lO-dien-3-yne-2,5- The diol was obtained as a crude product fc (6.9 g).

This diol was prepared without purification in dichloromethane (5
d) Dissolve 4C, pivalate chloride (2.6 g, 21
mmol), along with pyridine (5d) and 4-dimethylaminopyridine (U, 49 g, 4.0 mmol).
'OK and stirred for 50 minutes. Concentrate under reduced pressure and purify with a chromatograph (Clica gel, eluting with a mixed solvent of 7:1 to 5:1 of vinegar and vinegar to 5:1) to obtain (Pi).
, B) -5-pivaloyloxy-12-(tet2hydrobin-2-yl-2-yl)-2,6,10-trimethyldodeca-6,10-dien-3-yn-2-ol (5
, 7g, yield 68g) from the aldehyde.

IR (neat): 3395, 1734, 1145, 1
1201023 wounds.

NMR (CDCl, ): δ 1.21 (s,
9H), 1.4-1.8(m-)-s(δ 1,5
0)+1 (δ 1,68), 18H), 2.0
~2.3 (m, 4H), 3.50 (dt,
J=I O, 5, 4, 5Hz, IH), 3.
88 (dt, J=10.5°4.8Hz, IH)
, 4.00 (dd, J=12.3, 7.1
Hz, IH), 4.23 (dd, J=12.
3, 6.5Hz.

IH), 4.5-4.7 (m, IH), 5.36 (dd
.

J=6.5, 7. IHz, IH), 5.65
(t, J=6.2Hz, IH), 5.76(
s, IH).

+ M8 (m/z): 403 (M - OH, 1), 319 (
2).

216(6), 135(32), 85(100).

67(47), 57(100).

The obtained ester (1.2 g, 2.8 mmol) was dissolved in benzene (28d)K and mixed with silver tetrafluorophonate (57d, 0.29 mmol) at 80°C under the protection of visible light and ultraviolet light. Stirred for 1 hour and 30 minutes. Diluted with ether (50ml) and diluted with 5'% aqueous ammonia solution (
20id) and then washed with saturated saline (10a/d). After drying and concentrating, the power is 2 Muku C! Matog 2 Fee (
Curicaglu was purified with 2,2-dimethyl-((E,1
)-1,5-dimethyl-7-(nato2hydropicune-2
-Yelonium)hebut-1゜5-genyl)-3-pivaloyloxy-2,5-dihydro72one (0.65g,
A yield of 55% was obtained.

IR (neat): 1765, 1660, 1273, 1
148°1111.1079.11024a.

NMR (CDCI, ): δ 1,2g (s, 9H)
, 1.34 (s.

3H), 1.37 (s, 3H), 1.4
~1.8 (m-4-s(δ 1.60)+8(δ 1
, 6 g), 12H), 2.0 to 2.3 (m
, 4H), 3.49 (dt, J=ll, 7, 3.0; H
z, IH), 3.89 (dt, J=11.7, 5.3H
z.

IH), 3.99 (dd, J=11.9, 7.5Hz,
IH).

4.22 (dd, J=11.9, 5.OHz
, IH), 4.5-4.7 (m, IH),
5.13 (bz: s, IH), 5.2-5.
6 (m+dd (δ 5.36, J=5.U,
7.5Hz)-)-d(δ5.56, J=1
．． 7Hz), 3H).

10 MS (m/z): 336 (M-C5H80,2
), 335(6), 251(10), 167(16
), 85(68).

57 (100).

The obtained dihydrofuran compound (0.63 g, 1.50
mmo 1 ) was dissolved in ethanol (15 ml) and p
-Pyridinium toluenesulfonate (4 fuda, 0.1
9 mmol) at 50° C. for 1 hour and 30 minutes. Dilute with ether (100 d) and add incubation saline (10 d).
Washed with m). After drying and concentrating, it was purified by thin layer chromatography (silica gel, developing solvent: ethyl acetate/I/3:1) to give 2,2-dimethyl-5-((
E, B) -1,5-dimethyl-7-hydroxybuta-
1,5-genyl]-3-pivaloyloxy-2,5-
Dihydro72in (0.39 g, yield 771) was obtained.

IR(neat):3430,1767.1659,1
273°1147.1110,1026.1005cm
＋.

NMR (CDCI, ): δ 1.29 (s, 9H), 1
．． 34 (s.

3H), 1.37 (s, 3H), 1.60 (s, 3H)
.

1.68 (s, 3H), 2.0-2.3 (m, 4H),
4.14 (d, J==7.IHz, 2H),
5.1-5.2 (m, IH).

5.3 to 5.6 (m+t (δ 5,4 Ll,
J=7.1Hz)+d(δ5.58, J=1
．． 5Hz), 3H).

+ MS (m/z): 336 (M, 3), 321 (3),
237 (15), 167 (67), 153 (43), 1
13 (35), 85 (70), 57 (100), 43 (
44).

41(83).

Next, this alcohol body (u, 15 g, 0.45 m
mol ) and carbon tetrabromide (0.29 g, 0.88 mm
A solution of 2,tri-n-octylphosphine (0.33 g, 0.88 mmol) of 01) in ether (31111) was added at 0°C. After 10 minutes, carbon tetrabromide (51 mg, 0
．． 15 mmol), tri-n-octylphosphine (
51119.0.15 mmol) was added.

After stirring for 3 minutes, it was concentrated under reduced pressure and purified by 90 column chromatography (neutral alumina, elution with benzene) to give 5-((Iim,E)-7-broke-1,5-dimethyl. -1,5-genyl]-2,2-yyxthyl-3-bivaloyl
6 g, yield 92 g) was obtained.

1 liter (neat): 1765, 1657, 1273, 1
150°1109, IO280III.

NMR (CDCI, ): δ 1,28 (s, 9H), l
, 33 (s.

3H), 1.36 (s, 3H), 1.59 (s, 3H)
.

1.72 (s, 3H), 2.0-2.3 (m,
4H), 3.99 (d, J=8.7Hz, 2H)
, 5.12 (br s, IH).

5.3 to 5.7 (nn+d (δ 5,57 , J=
1.4Hz).

3H).

+ MS (m/z): 319 (M-Br, 6),
235(12).

167(13), 85(20), 57(100).

Example 1 Methyl 6-methylbenzoic acid in 3-boumo-5-chloro-2,4-diphthalate (0,55 g, 1.71 m-m
1.40Kt, 1.40Kt, 1.79M He=?Tene solution, 1.40Kt, 2.
5 mmol) was added over 20 minutes at -78°C. After 10 minutes, 3-methyl-1-butynyl steel (1)
(1,88 m-mol) of THF (3,8 m) −
A solution of hexay(1,05al)-he+samethylphosphoric triamide (0,40d) was added over 15 minutes. −
After stirring at 78°C for 30 minutes, 5-((E,B)-7
-Promo 1,5-dimethyl to but-1,5-genyl)-2,2-tumedel-3-piparoyl-2.5
-dihydro y -) y (t), 53g, 1.
A solution of 33 mmol) of THF (8d) was added. The mixture was stirred for 5 hours, heated to room temperature, and ether (150i*j) and saturated brine (15m) were added.

The organic layer was separated and the aqueous layer was extracted with ether (lOMtx3). The organic layers were combined and water (3d) - saturated brine (3
After washing twice with H1), it was dried and concentrated. Purify with 2 pieces of 1 thorn 2 pieces (silica gel, eluted with a mixed solvent of hequinane-ethyl acetate 15:1 to 1=1),
3-ri α-rho 4.6-simethoxy 5-((JR)-7
-(5,5-dimethyl-4-pivaloyloxy-2,5
--/Hitro-2-7ranyl)-3-methyl-2,6-
Methyl octagenyl-2-methylbenzoate (dihydro 7-lane form, 0.46 g, yield 6 from allyl bromide form)
In addition, 5-((E,E)-7-(5,5-dimethyl-4-oxotetrahydro-2-furanyl)-3-methyl- 2,6
-Methyl octagenyl-2-methylbenzoate (dihydrofluorone form, 639.7 lylpromide form, yield 1)
0) was also obtained O dihydrofuran body ■几(netecht): 1765, 1735, 1658, 1
586°1459.1322,1267.1158,1
096cm.

NM几(CDCIs): δ 1.26 (s, 9H), 1
．． 31 (s.

3H), 1.33 (s, 3H), 1.55 (s, 3H)
.

1.75 (s, 3H), 1.9-2.2 (m, 4H),
2.28 (s, 3H), 3.36 (d, J=7.IHz
, 2H).

3.72 (s, 3H), 3.77 (s, 3m), 3.8
8 (s.

3H), 5.0~5.2 (m+t(δ5
．． 15, J=7.1Hz), 2H), 5
．． 3 to 5.6 (m+d (δ 5,52°J=1.7
)(z), 2H).

+ H3 (m/z): 564 (M -) -2,2), 563
(2).

+ 562 (M, 5), 463 (5), 461 (10)
.

259(14), 257(3g), 85(37).

57 (100).

Calculated values for C3, H4, CIO; +
+M +2,564,2634;M.

62.26'? 4-.

＋ 　 　 　 　 ＋ Actual value: M-)-2,564,2553; M.

S62. 86° dihydrofuran compound IR (neat) 21755,1?35,1266.
1159°1093.996α.

NMR (CDCIg): δ1.22 (s, 3H)
, 1.28 (s.

3H), 1.62 (i, 3H), 1.77 (s, 3H)
.

1.9-2.3 (m, 4H), 2.28 (s, 3H).

2.39 (d, J=9.2Hz, IH), 2.40 (d
.

J = 7.5Hz, IH), 3.36(d
, J=6. (If(z.

2H), 3.75 (s, 3H), 3.80 (s, 3H)
.

3.91 (s, 3H), 4.49 (dd,
J=7.5, 9.2Hz, IH), 5.16(t, J
=6.6Hz, IH).

5.4-5.6 (m, IH).

+ + MS (m/z) = 480 (NL +2.3), 478 (
M.

? ), 446(7), 310(14), 281(37)
.

279 (100), 221 (2B), 135 (32).

56(41).

Example 2 ♀ + Lithium aluminum hydride A C5IIg, 0.13
The dihydrofuran compound obtained in Example 1 (24 da, 0
．． A solution of 0.43 mmol of ether (2 units) was added at O'0, and the mixture was stirred for 1 hour and 30 minutes. Lytecum aluminum hydride (5IRg, 0.13 mmol) was added to the mixture, and after stirring for 30 minutes, ether (15 ml) and saturated aqueous sodium sulfate solution (0.13 ml) were added. After removing the glaze, IN hydrochloric acid (3-) was added, and the mixture was extracted with ether (15ILtX2). The organic layers were combined, dried, concentrated, and purified by thin layer chromatography (Nrikaglu, developing solvent hexene-ethyl acetate 3:2).
7-5-((E,E)-7- in chloro-4,6-diphth)
(5,5-dimethyl-4-hydro-2-hydro-2-furanyl)-3-methyl-2,6-octadiyl)-2
-Methylbenzyl alcohol (monol form, 3 da, yield 13 thi) and 3-aryaI: I-4,6-nemethone 1
'-5-C(E,E)-7-(5,5-dimethyl-4
-human c1-IPsite2human c1-2-tucunyl)-
3-Methyl-2,6-octagenyl]-2-methylbenzyl alcohol (diol form, lzIRg, yield 60
%) were isolated.

Monool IR (neat): 3450.1755.1454.1
173°1097.1026.9900II.

NMR (CDCI, ): δ 1.22 (s, 3H), 1
．． 28 (s.

3H), 1.63 (s, 3H), 1.80 (s, 3H)
.

2.0-2.2 (m, 4H), 2.36 (d
, J=9.3Hz.

IH), 2.37 (d, J=7.1Hz,
LH), 2.46 (+a, 3H), 3.35 (s,
LH), 3.39 (d, J=6.5Hz, 2H), 3
．． 80 (s, 3H), 3.82 (s.

3H), 4.2-4.6 (m, IH), 4.
78 (s, 2H).

5.2Ll (t, J=6.5Hz, IH)
, 5.4-5.6 (m.

IH).

+ M8 (m/z): 452 (M +2.0.7), 4
50 (M.

1.2), 434(5), 432(13), 267(3
L)).

265 (81), 81 (52), 71 (6υ), 69 (
38), 55(100).

Diol IR (nea Rini 3390, 1450, 1227, 1
096°102L), 984 scratches.

NMi(, (CDCI3): δ 1,19(s, 3H
), 1.22 (s.

3H), 1.57 (s, 3M), 1.77 (s, 3H)
.

1.9-2.3 (m, 6H), 2.3-2.
6 (m+s (δ2.45), 5H), 3
．． 38 (d, J=6.71z, 2H).

3.78 (s, 3H), 3.82 (s, 3H), 3.9
1 (dd.

J=4.9,6. υHz, 114), 4.
2A4. ;a (m, IH).

4.76 (s, 2H), 5.19 (t, J=6.7H
z, 1k1).

5.3-5.5 (m, IH).

+ zvi8 (m/z): 454 (M −) −2,2), 4
52 (M, 5).

265 (29), 168 (35), 81 (46), 71
(11)L)), 55(9B).

Reference example 3 OCMe lithicium aluminum hydride (9,0.32m on 121
-mol) of:c-? /I/ (0,5d)
The ether of the dihydrofuran compound (45II9, 0.081 mmo 1 ) obtained in Example 1 was added to the Si suspension.
2m) solution was added at 0°C and stirred for 10 minutes. To this, lithium aluminum hydride A (34,0,080 mmol
) was added. After 10 minutes, diluted with ether (10m) and added saturated aqueous sodium sulphate (0.3d). IN salt to the rest (after removing the upper part)! (3ju) was strained and extracted with diku aa meme/(5+a/X3). The organic layers were combined, dried and concentrated, and the resulting residue (37) was dissolved in dichloromethane (3aj), and sodium acetate A (74mg,
0.90 mmol), pyridium chloride (0.17 g, 0.79 mmol)
) for 151 minutes. Ether (50Ht
) and purified on a 2-meter chromatogram (top 2 columns and silica gel, eluted with ether) to give 3-chloroa
-4゜6-diphthoxylic-2-methyl-5-((E,B)
-3-Methyl-7-(nato2hydro5,5-dimethyl-4-oheino-2-)2nyl)-2,6-octagenyl]benzaldehyde (4.6-0-
Dimethyl form, 334. A yield of 92% was obtained from the dihydrofuran compound.

IR (neat): 1755, 1695, 1378, 1
31U.

1228.11098a.

NMR (CDCI, ): δ 1.23 (s, 3H), 1
．． 29 (s.

3H), 1.64 (a, 3H), 1.81 (s, 3H)
.

2.0-2.2 (m, 4H), 2.43 (d, J=9.
3Hz.

IH), 2.44 (d, J=7.2Hz, IH), 2.
65 (s, 3H), 3.42 (d, J=6.6Hz, 2
H).

3.85 (s, 3H), 3.91 (s, 3H), 4.5
4 (dd, J=7.2, 9.3Hz, IH), 5.20
(t.

J=6.6Hz, IH), 5.55(t, J=6.2H
z.

IH), 10.46 (s, IH).

+ + MS (m/z): 450 (M +2.6), 448 (M
.

13), 363 (7), 281 (54), 249 (42
).

227 (100), 135 (82), 81 (71).

55 (95).

Reference Example 4 A mixture of about 4:6 of monool and diol obtained in Example 2* (23#, about 0.052 mmol) was dissolved in dichloromethane (2iu)K. Sodium acetate (56
Add pyridinicum chloride chromate (899, +3.41 mmol) to a 59,0,68r* plate at 0°C,
The mixture was stirred at room temperature for 20 minutes. Add chromium chloride pyridinium A (C2219.0, ILlmmol) to the grains and make 1
After stirring for 5 minutes, ◎ether (20aO) was added to obtain a column chromadog27ter compound (22da, yield 496%).This compound showed the same spectral data as the compound obtained in Reference Example 3 and was rounded. .

Reference Example 5 HO Lithium aluminum hydride (12II9, 0.32m
The dihydrofuranone compound obtained in Example 1 (38IR9, U
, U80mmo 1 ) in ether,z(2ILt) was added at 0°C and stirred for 20 minutes. Ether (10IL
diluted with saturated sodium sulfate')cum aqueous solution (0,21
Lt) was added. After removing the supernatant), add IN hydrochloric acid (3
iii) t-added and extracted with ether (xsmx2). The organic layers were combined, dried, and concentrated to obtain a residue (36IJ
9) was dissolved in dichloromethane (3m) and sodium acetate (74IIg).

0.90 mmol), pyridinium chloride chromate (0,
17 g, 0.79 mmol) for 15 minutes. It was diluted with ether (50d) and purified with 2mukuroi toge2fee (Celite and silica gel, eluted with ether) to give the 4,6-0-dimethyl form of Asco727n (3
4III9. A yield of 95% was obtained. This is reference example 3
It showed the same spectral data as the compound obtained in .

November 7, 1985 Michibe Uga, Director General of the Patent Office, 1, Indication of the case, Patent Application No. 274140 filed in 1982, 2, Name of the invention: Hexa-substituted benzene derivatives 3, Description of the person making the amendment Column 5 of "Detailed Description of the Invention", Contents of the Amendment 1) "ノ" in line 3 on page 3 of the specification of the present application is corrected to rn1.

that's all

Claims (1)

[Claims] Hexasubstituted benzene derivatives represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. Yes, X is a group represented by ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲A group represented by ▼There are mathematical formulas, chemical formulas, tables, etc., or ▲A group represented by ▼There are mathematical formulas, chemical formulas, tables, etc. (In the formula, R^3 is an alkyl group.) ]