CN102321050A - Gypsy moth sex pheromone synthesis method - Google Patents
Gypsy moth sex pheromone synthesis method Download PDFInfo
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Abstract
The invention relates to a gypsy moth sex pheromone synthesis method, in particular to an epoxy propane compound synthesis method. The invention aims at proving the gypsy moth sex pheromone synthesis method which has the advantages of taking a cheap and easily-obtained 2-propargyl alcohol (1) as a raw material, no protecting group, high efficiency, high enantioselectivity, high yield and simple synthesis process. According to the invention, the gypsy moth sex pheromone is I [(+)-(7R,8S)-7,8-epoxy-2-methyl group octadecane] and the enantiomer II [(-)-(7R,8S)-7,8-epoxy-2-methyl group octadecane] of the I [(+)-(7R,8S)-7,8-epoxy-2-methyl group octadecane]; (7R,8S)-I is synthesized with a total yield of 29 percent through a reaction of six steps, and the enantiomer is excess of which e.e is more than 98 percent; and (7R,8S)-II is synthesized with a total yield of 27 percent through the reaction of six steps, and the enantiomer is excess of which the e.e is more than 99 percent.
Description
Technical field
The present invention relates to a kind of compound method of propylene oxide compound; Especially relate to a kind of synthetic gypsymoth sex pheromone I [(+)-(7R, 8S)-7,8-epoxy-2-methyl octadecane] and enantiomorph II [(-)-(7S thereof; 8R)-7,8-epoxy-2-methyl octadecane] method.
Background technology
Gypsymoth has another name called the swing caterpillar, and apple poison moth, persimmon caterpillar are the worldwide injurious forest-insects that a kind of feeding habits are very wide, harm is very big, and it has characteristics such as feeding habits are assorted, distribution is wide, harm is heavy, larva moves with the wind.Gypsymoth is taken place general in Europe, North America and harm is also bigger, and larva can be with the leaf eat everything up when serious.Simultaneously, it also is the big important pests of China forest, gardens, silkworm industry, fruit tree.Except that northern China endangers, on Xiamen, Fujian, Putian, Jiangxi and other places reporting of harm arranged also in recent years, production has caused great financial loss to eagroforestry.Therefore, searching effectively preventing method is very important.
Adopt the method for disparlure, not only can trap gypsymoth very effectively, reach the purpose that reduces the gypsymoth insect pest, and with respect to the method for conventional spray agricultural chemicals, can not pollute environment, insect can not produce significant resistance yet.
People such as Bierl (Bierl, B.A.; Beroza, M.; Collier, C.W.Science 1970,170; 87) separated in the female gypsymoth body in 1970 and the structure that identifies the gypsymoth sex pheromone is I [(+)-(7R, 8S)-7,8-epoxy-2-methyl octadecane]; Its physiologically active is with its enantiomorph II [(-)-(7S; 8R)-7,8-epoxy-2-methyl octadecane] just opposite, bigger tens times than racemic.Therefore many for many years chemistry and biological worker are devoted to synthetic high optically pure gypsymoth sex pheromone.
Up to now, existing several different methods is applied to the synthetic of such epoxy compounds, and the main compound method of having reported is following:
1979, the K.Mori of Tokyo Univ Japan (Mori, K.; Takigawa, T.; Matsui, M.Tetrahedron 1979,35,833) be that raw material sets out with natural L-(+)-tartrate, waited for 12 steps reacted through Wittig (Wittig) and synthesized compound I that overall yield reaches 5%.Its synthetic route is following:
The shortcoming of this method is that synthetic route is oversize, and productive rate is low, and atom utilization is low.It is the p-methyl benzenesulfonic acid ester group that compound is write a Chinese character in simplified form OTs, i-Am
2CuLi is an organic copper lithium reagent, BCl
3Be boron trichloride, CH
2Cl
2Be methylene dichloride, THP is a tetrahydropyrans protection base, i-Bu
2AlH is a diisobutyl aluminium hydride, n-C
8H
17PPh
3Br is the phosphonium ylide reagent of octane, and n-BuLi is a n-Butyl Lithium, and THF is a THF, and Pd/C is the palladium charcoal, H
2Be hydrogen, TsCl is a p-methyl benzene sulfonic chloride, C
5H
5N is a pyridine, and TsOH is a p-methyl benzenesulfonic acid, and MeOH is a methyl alcohol, and KOH is a Pottasium Hydroxide.
People (Lin, G.-Q. such as woods Guoqiang in 1984; Wu, B.-Q.; Liu, L.-Y.; Wang, X.-Q.; Zhou, W.-S.Acta Chim.Sinica (Engl.Ed.) 1984,42 (8), 797) be raw material with (+)-glyceraldehyde acetonide, with the Grignard reagent addition of 1-bromo-decane; Nine steps reaction such as the addition open loop of organic copper lithium reagent and epoxy has been accomplished the synthetic of compound I with 30% productive rate.Its synthetic route is following:
Compound write a Chinese character in simplified form n-C
10H
21MgBr is the Grignard reagent of 1-bromo-decane, and NaH is a sodium hydrogen, and DMSO is a methyl-sulphoxide, and BzCl is a Benzoyl chloride 99min., and HCl is a hydrochloric acid, H
2O is a water, and Py is a pyridine, [(CH
3)
2CH (CH
2)
3]
2CuLi is an organic copper lithium reagent, and HBr is a hydrogen bromide, and HOAc is an acetic acid.
K.Mori (Mori, K. in 1986; Ebata, T.Tetrahedron 1986,42,3471) through summer Price (Sharpless) asymmetric Epoxidation, with organic copper lithium reagent repeatedly nine steps reaction such as addition synthesized compound I, overall yield reaches 12%.Its synthetic route is following:
The shortcoming of this method is that synthetic route is oversize, and productive rate is low, repeatedly uses organic copper lithium reagent, and reagent is relatively more expensive, and toxicity is bigger, and epoxidised stereoselectivity is bad, and the superfluous e.e. of enantiomorph has only 84%.Compound is write a Chinese character in simplified form i-Am
2CuLi is an organic copper lithium reagent, and Pd is a palladium, BaSO
4Be permanent white, quinoline is a quinoline, (n-C
9H
19)
2CuLi is an organic copper lithium reagent.
K.Mori (Brevet, J.L. in 1992; Mori, K.Synthesis 1992,1007) with the cis-butenediol raw material, confirmed the stereochemistry of epoxy compounds through the chiral separation of enzyme, afterwards through having introduced the two ends side chain of gypsymoth sex pheromone respectively with the coupling of organic copper lithium reagent.Synthesized compound I with 29% productive rate, the superfluous e.e. of enantiomorph＞99% through ten steps.Its synthetic route is following:
It is tert-butyl diphenyl chlorosilane that compound is write a Chinese character in simplified form TBDPSCl, and DMAP is the 4-Dimethylamino pyridine, Et
3N is a triethylamine, and TBAF is a tetrabutyl ammonium fluoride, Et
2O is an ether.
People (Marshall, J.A. such as Marshall in 1999; Jablonowski, J.A.; Jiang, H.J.J.Org.Chem.1999,64,2152) with α, beta-unsaturated aldehyde is a raw material, has synthesized compound I with 26% productive rate through six steps, has synthesized compound I I with 20% productive rate through nine steps.Its synthetic route is following:
The shortcoming of this method is to use the tin reagent of comparison poison, and is unfriendly to environment, and the superfluous e.e. of its enantiomorph also has only 90%.Compound write a Chinese character in simplified form Bu
3SnLi is an organotin reagent, (S)-BINAL-H is the chiral reduction agent, TBSOTf is a tertiary butyl dimethylsilyl triflate, BF
3OEt
2Be etherate of trifluoroboron, Rh is a rhodium, Al
2O
3Be alchlor, Triton-B is a benzyltrimethylammonium hydroxide.
People (Prasad, K.R. such as K.Prasad in 2007; Anbarasan; P.J.Org.Chem.2007,72,3155) be that raw material sets out with L-(+)-tartrate; Made up the skeleton of compound I and II with key intermediate chirality allyl alcohol derivatives and alkene generation olefin metathesis; Close cyclization again and become compound I, through ten single step reactions, productive rate is 34%; Synthesized compound I I, through the reaction of ten steps, productive rate is 35%.Its synthetic route is following:
The shortcoming of this method is that step is oversize, and the reagent of using is like Grubbs 2nd catalyzer costliness very, and is economical inadequately.The TBDMSOTf that writes a Chinese character in simplified form of compound is a tertiary butyl dimethylsilane sulphonate, and Grubbs 2nd gen.catalyst is the catalyzer of s-generation olefin metathesis, and Bn is a benzyl.
It is that starting raw material is perhaps used some chiral catalysts, enzyme catalyst that above compound method mainly comprises with optically pure natural product, transforms through multistep, could make up chiral centre, synthesizes thereby accomplish it; Yet most of steps are longer, and efficient is low, and are economical inadequately, also will use the comparison poison sometimes, to the disagreeableness reagent of environment.
Summary of the invention
It is raw material with 2-propynol (1) cheap and easy to get that the object of the invention aims to provide a kind of, unprotect base, high-level efficiency, high enantioselectivity and high yield, the compound method of the gypsymoth sex pheromone that synthesis technique is easy.
Said gypsymoth sex pheromone is I [(+)-(7R, 8S)-7,8-epoxy-2-methyl octadecane] and enantiomorph II thereof [(-)-(7S, 8R)-7,8-epoxy-2-methyl octadecane].
The synthetic route of said gypsymoth sex pheromone is:
In following statement, specific synthetic product is according to the numbering in the structural formula, representes that with Arabic numeral R or S represent the absolute configuration of compound ,+or-optical direction of expression compound.N representes the alkyl of straight chain, and OTf representes the trifluoromethayl sulfonic acid ester group.
The compound method of said gypsymoth sex pheromone may further comprise the steps:
1) under-80～20 ℃, compound 1 in a kind of ether solvent, under highly basic and complexing agent effect with 1-bromo-decane generation linked reaction, through extraction, dry, concentrate, obtain white solid compound 2 behind the purifying;
2) under 0～30 ℃, catalytic hydrogenation reaction takes place in compound 2 under the lindlar catalyst effect in a kind of lower boiling alkane solvent saturated by hydrogen, through filtering, concentrate, obtaining colourless liquid compound 3 behind the purifying;
3) under-40～20 ℃, Sharp's this (Sharpless) asymmetric epoxidation reaction of Lay takes place in compound 3 under catalyzer and oxygenant effect in a kind of halogenated hydrocarbon solvent, through extraction, dry, concentrate, obtain white solid compound 4 behind the purifying;
4) under-80～20 ℃, compound 4 in a kind of halohydrocarbon or ether solvent, under the organic bases effect, with the reaction of a kind of sulphonic acid anhydride, through extraction, dry, concentrate, obtain colourless liquid compound 5 behind the purifying;
5) under-80～20 ℃, compound 5 in a kind of ether solvent, under highly basic and complexing agent effect with 4-methyl pentyne generation linked reaction, through extraction, dry, concentrate, obtain colourless liquid compound 6 behind the purifying;
6) under 0～40 ℃, catalytic hydrogenation reaction takes place in compound 6 under catalyst action in a kind of lower boiling alkane solvent saturated by hydrogen, through filtration, concentrate, obtain behind the purifying colourless liquid compound (7R, 8S)-I;
7) under-40～20 ℃, Sharp's this (Sharpless) asymmetric epoxidation reaction of Lay takes place in compound 3 under catalyzer and oxygenant effect in a kind of halogenated hydrocarbon solvent, through extraction, dry, concentrate, obtain white solid compound 7 behind the purifying;
8) under-80～20 ℃, compound 7 in a kind of halohydrocarbon or ether solvent, under the organic bases effect, with the reaction of a kind of sulphonic acid anhydride, through extraction, dry, concentrate, obtain colourless liquid compound 8 behind the purifying;
9) under-80～20 ℃, compound 8 in a kind of ether solvent, under highly basic and complexing agent effect with 4-methyl pentyne generation linked reaction, through extraction, dry, concentrate, obtain colourless liquid compound 9 behind the purifying;
10) under 0～40 ℃, catalytic hydrogenation reaction takes place in compound 9 under catalyst action in a kind of lower boiling alkane solvent saturated by hydrogen, through filtration, concentrate, obtain behind the purifying colourless liquid compound (7S, 8R)-II.
In step 1), said ether solvent can be selected from C
2～C
4Aliphatic ether or alicyclic ether etc., particularly ether or THF etc.; Said highly basic can be n-Butyl Lithium etc.; Said complexing agent can be hexamethylphosphoramide etc.; Said extraction agent can be selected ether etc. for use; Said dried reagent can be selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate etc. for use; Said compound 1: highly basic: complexing agent: the mol ratio of 1-bromo-decane can be 1: (2～2.5): (2～3): (1～1.5).
In step 2) in, said lower boiling alkane solvent can be selected from C
5～C
6Aliphatics saturated alkane etc., particularly hexanaphthene or normal hexane etc.; Said lindlar catalyst can be selected from the palladium metal that metallic lead is poisoned or quinoline is poisoned etc., and the lindlar catalyst carrier is lime carbonate or permanent white etc.Said compound 2: the massfraction ratio of catalyzer can be (5～20): 1.
In step 3), said halogenated hydrocarbon solvent can be selected from C
1～C
4Halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Said catalyzer can select for use tetra isopropyl oxygen titanium, D-tartrate diisopropyl ester, D-tartrate diethyl ester,
Molecular sieve,
Molecular sieve, 300～400 purpose silica gel or hydrolith etc.; Said oxygenant can be the nonane solution of anhydrous tertbutanol peroxide etc.; Said extraction agent can be selected methylene dichloride etc. for use; Said dried reagent can be selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate etc. for use; Said compound 3: tetra isopropyl oxygen titanium: D-tartrate: the mol ratio of tertbutanol peroxide can be 1: (1～1.5): (1～1.5): (2～3).
In step 4), said halogenated hydrocarbon solvent can be selected from C
1～C
4Halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Said ether solvent is selected from C
2～C
4Aliphatic ether or alicyclic ether etc., particularly ether or THF etc.; Said organic bases can be selected tertiary amine etc., particularly imidazoles, pyridine or triethylamine etc. for use; Said sulphonic acid anhydride can be selected Trifluoromethanesulfonic anhydride etc. for use; Said extraction agent can be selected methylene dichloride etc. for use; Said dried reagent can be selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate etc. for use; Said compound 4: organic bases: the mol ratio of sulphonic acid anhydride can be 1: (3～4): (3～4).
In step 5), said ether solvent can be selected from C
2～C
4Aliphatic ether or alicyclic ether etc., particularly ether or THF etc.; Said complexing agent can be hexamethylphosphoramide etc.; Highly basic can be n-Butyl Lithium etc.; Said extraction agent can be selected ETHYLE ACETATE etc. for use; Said dried reagent can be selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate etc. for use; Said compound 5: highly basic: complexing agent: the mol ratio of 4-methyl pentyne can be 1: (2～2.5): (2～2.5): (2～2.5).
In step 6), said lower boiling alkane solvent can be selected from C
5～C
6Aliphatics saturated alkane etc., particularly hexanaphthene or normal hexane etc., said catalyzer is a palladium charcoal etc.; Said compound 6: the massfraction ratio of catalyzer can be (5～20): 1.
In step 7), said halogenated hydrocarbon solvent can be selected from C
1～C
4Halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Said catalyzer can select for use tetra isopropyl oxygen titanium, L-tartrate diisopropyl ester, L-tartrate diethyl ester,
Molecular sieve,
Molecular sieve, 300～400 purpose silica gel or hydrolith etc.; Said oxygenant can be the nonane solution of anhydrous tertbutanol peroxide etc.; Said extraction agent can be selected methylene dichloride etc. for use; Said dried reagent can be selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate etc. for use; Said compound 3: tetra isopropyl oxygen titanium: L-tartrate: the mol ratio of tertbutanol peroxide can be 1: (1～1.5): (1～1.5): (2～3).
In step 8), said halogenated hydrocarbon solvent can be selected from C
1～C
4Halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Said ether solvent is selected from C
2～C
4Aliphatic ether or alicyclic ether etc., particularly ether or THF etc.; Said organic bases can be selected tertiary amine etc., particularly imidazoles, pyridine or triethylamine etc. for use; Said sulphonic acid anhydride can be selected Trifluoromethanesulfonic anhydride etc. for use; Said extraction agent can be selected methylene dichloride etc. for use; Said dried reagent can be selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate etc. for use; Said compound 7: organic bases: the mol ratio of sulphonic acid anhydride can be 1: (3～4): (3～4).
In step 9), said ether solvent can be selected from C
2～C
4Aliphatic ether or alicyclic ether etc., particularly ether or THF etc.; Said complexing agent can be hexamethylphosphoramide etc.; Highly basic can be n-Butyl Lithium etc.; Said extraction agent can be selected ETHYLE ACETATE etc. for use; Said dried reagent can be selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate etc. for use; Said compound 8: highly basic: complexing agent: the mol ratio of 4-methyl pentyne can be 1: (2～2.5): (2～2.5): (2～2.5).
In step 10), said lower boiling alkane solvent can be selected from C
5～C
6Aliphatics saturated alkane etc., particularly hexanaphthene or normal hexane etc., said catalyzer is a palladium charcoal etc.Said compound 9: the massfraction ratio of catalyzer can be (5～20): 1.
The present invention is a raw material with 2-propynol (1) cheap and easy to get, efficient, high enantioselectivity, high productivity synthesized the gypsymoth sex pheromone (7R, 8S)-I and enantiomorph thereof (7S, 8R)-II.Each procedure of the present invention, separate simply, productive rate is high, and used reagent is common agents, and is cheap and easy to get, and need not use the protection base, and route is shorter, is fit to mass production.Through 6 step reactions with 29% overall yield synthesized (7R, 8S)-I, the superfluous e.e. of enantiomorph＞98%; Through 6 step reactions with 27% overall yield synthesized (7S, 8R)-II, the superfluous e.e. of enantiomorph＞99%.
Embodiment
Through embodiment the present invention is further described below.
Embodiment 1
Step 1 Synthetic 2-alkynes 13 carbon-1-alcohol (2)
With 2-propynol (1) (280mg 5mmol) is dissolved in THF (50mL) solvent ,-78 ℃ with argon atmospher under drip n-Butyl Lithium (4.7mL, 10.5mmol, 2.2Min hexane).Behind-78 ℃ of reaction 60min, (11mL, 5.5mmol) (2.3mL 13.3mmol), reacts 5h then under uniform temp with hexamethylphosphoramide to drip the 1-bromo-decane successively.After 10mL saturated sodium carbonate solution cancellation reaction, separatory, water is with ether (2 * 20mL) extracted twice.The organic phase that merges is used anhydrous sodium sulfate drying, and through filtering, concentrating under reduced pressure obtains compound 2 (823mg, 84%) behind the purification by silica gel column chromatography.White solid, Mp.30-31 ℃ (normal hexane); IR (film) v
Max3326 (OH), 2927,2853,2219 (w, C ≡ C), 1464,1375,1138,1016cm
-1 1H-NMR (400MHz, CDCl
3) δ 0.88 (t, J=6.8Hz, 3H, CH
3), 1.22-1.42 (m, 14H, C
7H
14CH
3), 1.46-1.56 (m, 3H, C (5)-H, OH), 2.21 (tt, J=2.1,7.1Hz, 2H, C (4)-H), 4.25 (br, 2H, CH
2OH) ppm;
13C-NMR (100MHz, CDCl
3) δ 14.1,18.7,22.7,28.6,28.9,29.1,29.3,29.5,29.6,31.9,51.4,76.7,86.7ppm; MS (ESI) m/z 219.1 (M+Na
+).
Step 2 is synthesized (Z)-2-alkene 13 carbon-1-alcohol (3)
0～5 ℃ with nitrogen atmosphere under, adding compound 2 (30mg, normal hexane 0.15mmol) (2mL) solution, 0～5 ℃ of reaction to lindlar catalyst (5mg) in.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid 3 (28.5mg, 94%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.IR(film)v
max?3329(br，OH)，3015，2927，2847，1658(w，C＝C)，1466，1384，1015cm
-1；
1H-NMR(400MHz，CDCl
3)δ0.88(t，J＝6.8Hz，3H，C
8H
16CH
3)，1.24-1.37(m，17H，OH，C
8H
16CH
3)，2.06(m，2H，CH
2C
9H
19)，4.19(d，J＝6.1Hz，2H，CH
2OH)，5.56(m，2H，CH＝CH)ppm；
13C-NMR(100MHz，CDCl
3)δ14.1，22.7，27.4，29.2，29.3，29.47，29.59(2C)，29.68，31.9，58.6，128.3，132.9ppm；MS(ESI)m/z?221.2(M+Na
+，100％)。
Step 3 synthetic (2R, 3S)-2,3-epoxy 13 carbon-1-alcohol (4)
Under the argon atmospher protection, 83mg silica gel mixing 63mg hydrolith injects exsiccant dichloromethane solvent and tetra isopropyl oxygen titanium (4.9mL; 16.7mmol);-25 ℃ are stirred down, and every afterwards separated 20min drips D-(-)-tartrate diisopropyl ester (4.2g, methylene dichloride 18.0mmol) (5mL) solution, (Z)-2-alkynes 13 carbon alcohol 2 (2.74g successively; 13.8mmol) methylene dichloride (5mL) solution, nonane (5.5mL) solution of tertbutanol peroxide (30.4mmol), subsequently in-25 ℃ of reactions 3 days.After 40mL 10% tartaric aqueous solution cancellation reaction, slowly heat up, separatory, water is with methylene dichloride (2 * 50mL) extracted twice.(through anhydrous sodium sulfate drying, filter, and concentrating under reduced pressure obtains compound 4 (1.78g, 60%) behind the silica gel column chromatography by 3 * 10mL) washings three times with saturated aqueous common salt for the organic layer that merges.White solid, R
f0.3 (ethyl acetate: petroleum ether=1: 3); Mp.62-63 ℃ (sherwood oil); [α]
D 20-7.9 (c 1.0, EtOH); IR (film) v
Max3427 (br, OH), 2911,2850,1634,1469,1042cm
-1 1H-NMR (400MHz, CDCl
3) δ 0.88 (t, J=6.9Hz, 3H, CH
3), 1.20-1.60 (m, 18H, C
9H
18CH
3), 1.61-1.68 (m, 1H, OH), 3.01-3.06 (ddd, J=6.6,5.5,4.2Hz, 1H, C (3)-H), 3.16 (ddd, J=4.2,4.2,6.9Hz, 1H, C (2)-H), 3.68 (ddd, J=2.0,6.9,11.8Hz, 1H, CH
2OH), 3.86 (ddd, J=4.2,7.6,11.8Hz, 1H, CH
2OH) ppm;
13C-NMR (100MHz, CDCl
3) δ 14.1,22.7,26.6,27.95,29.3,29.4,29.48,29.51,29.55,31.9,56.7,57.3,60.9ppm; MS (ESI) m/z 237.2 (M+Na
+, 100%); HRMS (ESI) calcd for C
13H
26NaO
2 +[M+Na
+]: 237.1825, found:237.1829.
Step 4 synthetic (2R, 3S)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid ester (5)
With compound 4 (250mg 1.17mmol) is dissolved in methylene dichloride (65mL) solvent, in-78 ℃ with argon atmospher under add triethylamine (0.6mL successively; 4.21mmol) and Trifluoromethanesulfonic anhydride (0.58mL; 3.5mmol), react to the solution clarification ,-78 ℃ are continued about half h of reaction down.After 5mL saturated ammonium chloride solution cancellation reaction, separatory, water is with methylene dichloride (2 * 20mL) extracted twice.(through anhydrous sodium sulfate drying, filter, and concentrating under reduced pressure gets colourless liquid 5 (354mg, 88%) behind the purification by silica gel column chromatography by 2 * 5mL) washed twice with saturated aqueous common salt for the organic phase that merges.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶50)。
Step 5 synthetic (7R, 8S)-7,8 epoxies-2-methyl octadecane-4-alkynes (6)
With 4 methyl pentynes (0.24mL 2.0mmol) is dissolved in ether (15mL) solvent ,-78 ℃ with argon atmospher under drip n-Butyl Lithium (0.83mL, 1.82mmol, 2.2M in hexane).Behind-78 ℃ of reaction 10min, (350mg, (0.4mL 2.3mmol), reacts 1h then under uniform temp for diethyl ether solution 1.0mmol) (2mL) and hexamethylphosphoramide to drip compound 5 successively.After 2mL saturated ammonium chloride solution cancellation reaction, separatory, water is with ETHYLE ACETATE (3 * 10mL) extractions three times.The organic phase that merges is used anhydrous sodium sulfate drying, and through filtering, concentrating under reduced pressure obtains colourless liquid 6 (236mg, 85%) behind the purification by silica gel column chromatography.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶50)；[α]
D 20-47.2(c1.0，CHCl
3)；IR(film)v
max?2957，2924，2850，2278(W，C≡C)，1592，1464，1384，1022cm
-1；
1H-NMR(400MHz，CDCl
3)δ0.87(t，J＝6.9Hz，3H，C
9H
18CH
3)，0.95(d，J＝6.6Hz，6H，CH(CH
3)
2)，1.20-1.60(m，18H，C
9H
18CH
3)，1.77(Sept，J＝6.6Hz，1H，CH(CH
3)
2)，2.04(dt，J＝6.5，2.4Hz，2H，CH
2CH(CH
3)
2)，2.23(ddt，J＝16.9，7.4，2.4Hz，1H，C(6)-H)，2.57(ddt，J＝16.9，5.0，2.4Hz，1H，C(6)-H)，2.94(dt，J＝4.2，5.9Hz，1H，C(8)-H)，3.10(ddd，J＝4.2，5.0，7.4Hz，1H，C(7)-H)ppm；
13C-NMR(100MHz，CDCl
3)δ14.1，18.7，21.9(2C)，22.6，26.4，27.5，27.9，28.1，29.3，29.47，29.51(2C)，29.6，31.9，55.4，57.0，75.7，81.2ppm；MS(ESI)m/z?301.2(M+Na+，100％)；HRMS(ESI)calcd?for?C
19H
34NaO+[M+Na
+]：301.2502，found：301.2506。
Step 6 synthesize (+)-(7R, 8S)-7,8 epoxies-2-methyl octadecane (I)
0～5 ℃ with nitrogen atmosphere under, (6mg, (57mg, normal hexane 0.2mmol) (1mL) solution is in 25 ℃ of reactions to add compound 6 in 10wt%) to palladium-carbon catalyst.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid I (47mg, 81%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶100)；[α]
D 20+1.0(c?1.0，CCl
4)；IR?(film)v
max?2951，2924，2854，1464，1378，1263，1098，1021cm
-1；
1H-NMR(400MHz，CDCl
3)δ0.91-0.84(m，9H)，1.15-1.59(m，27H)，2.84-2.94(m，2H)ppm；
13C-NMR(100MHz，CDCl
3)δ14.1，22.57，22.58，22.7，26.6，26.8，27.3，27.81，27.84，27.87，29.3，29.54，29.58，31.9，38.9，57.2ppm；MS(ESI)m/z?305.3(M+Na
+，100％)；HRMS(ESI)calcd?for?C
19H
38NaO
+[M+Na
+]：305.2815，found：305.2811。
Step 7 synthetic (2S, 3R)-2,3-epoxy 13 carbon-1-alcohol (7)
Under the argon atmospher protection, 95mg silica gel mixing 71mg hydrolith injects exsiccant dichloromethane solvent and tetra isopropyl oxygen titanium (5.6mL; 18.2mmol); Under-25 ℃, every separated 20min drips L-(+)-tartrate diisopropyl ester (4.8g, methylene dichloride 20.6mmol) (5mL) solution, (Z)-2-alkynes 13 carbon alcohol 2 (3.14g successively; 15.8mmol) methylene dichloride (5mL) solution, nonane (6.3mL) solution of tertbutanol peroxide (34.9mmol), subsequently in-25 ℃ of reactions 3 days.After 40mL 10% tartaric aqueous solution cancellation reaction, slowly heat up, separatory, water is with methylene dichloride (2 * 50mL) extracted twice.(through anhydrous sodium sulfate drying, filter, and concentrating under reduced pressure obtains compound 7 (2.06g, 61%) behind the silica gel column chromatography by 3 * 10mL) washings three times with saturated aqueous common salt for the organic layer that merges.White solid, R
f0.3 (ethyl acetate: petroleum ether=1: 3); Mp.62-63 ℃ (sherwood oil); [α]
D 20+ 7.9 (c 1.0, EtOH) IR (film) v
Max3427 (br, OH), 2911,2850,1634,1469,1042cm
-1 1H-NMR (400MHz, CDCl
3) δ 0.88 (t, J=6.9Hz, 3H, CH
3), 1.20-1.60 (m, 18H, C
9H
18CH
3), 1.91 (br, 1H, OH), 3.01-3.06 (ddd, J=6.6,5.5,4.2Hz, 1H, C (3)-H), 3.16 (ddd, J=4.2,4.2,7.0Hz, 1H, C (2)-H), 3.67 (ddd, J=2.0,7.0,11.8Hz, 1H, CH
2OH), 3.86 (ddd, J=4.2,7.6,11.8Hz, 1H, CH
2OH) ppm;
13C-NMR (100MHz, CDCl
3) δ 14.1,22.6,26.6,27.95,29.3,29.4,29.48,29.50,29.55,31.9,56.8,57.3,60.9ppm; MS (ESI) m/z 237.2 (M+Na
+, 100%); HRMS (ESI) calcd for C
13H
26NaO
2 +[M+Na
+]: 237.1825, found:237.1828.
Step 8 synthetic (2S, 3R)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid ester (8)
With compound 7 (100mg 0.47mmol) is dissolved in methylene dichloride (26mL) solvent, in-78 ℃ with argon atmospher under add triethylamine (0.24mL successively; 1.68mmol) and Trifluoromethanesulfonic anhydride (0.23mL; 1.40mmol), react to the solution clarification ,-78 ℃ are continued about half h of reaction down.After 5mL saturated ammonium chloride solution cancellation reaction, separatory, water is with methylene dichloride (2 * 20mL) extracted twice.(through anhydrous sodium sulfate drying, filter, and concentrating under reduced pressure gets colourless liquid 8 (138mg, 85%) behind the purification by silica gel column chromatography by 2 * 5mL) washed twice with saturated aqueous common salt for the organic phase that merges.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶50)。
Step 9 synthetic (7S, 8R)-7,8 epoxies-2-methyl octadecane-4-alkynes (9)
With 4 methyl pentynes (0.07mL 0.56mmol) is dissolved in ether (3mL) solvent ,-78 ℃ with argon atmospher under drip n-Butyl Lithium (0.23mL, 0.50mmol, 2.2M in hexane).Behind-78 ℃ of reaction 10min, (100mg, (0.11mL 0.64mmol), reacts 1h then under uniform temp for diethyl ether solution 0.28mmol) (1mL) and hexamethylphosphoramide to drip compound 8 successively.After 1mL saturated ammonium chloride solution cancellation reaction, separatory, water is with ETHYLE ACETATE (3 * 10mL) extractions three times.The organic phase that merges is used anhydrous sodium sulfate drying, and through filtering, concentrating under reduced pressure obtains colourless liquid 9 (66mg, 85%) behind the purification by silica gel column chromatography.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶50)；[α]
D 20+47.2(c?1.0，CHCl
3)；IR?(film)v
max?2957，2924，2850，2278(w，C≡C)，1592，1464，1384，1022cm
-1；
1H-NMR(400MHz，CDCl
3)δ0.87(t，J＝6.8Hz，3H，C
9H
18CH
3)，0.95(d，J＝6.6Hz，6H，CH(CH
3)
2)，1.20-1.60(m，18H，C
9H
18CH
3)，1.76(Sept，J＝6.6Hz，1H，CH(CH
3)
2)，2.04(dt，J＝6.5，2.4Hz，2H，CH
2CH(CH
3)
2)，2.23(ddt，J＝16.9，7.4，2.4Hz，1H，C(6)-H)，2.57(ddt，J＝16.9，5.0，2.4Hz，1H，C(6)-H)，2.94(dt，J＝4.2，5.9Hz，1H，C(8)-H)，3.10(ddd，J＝4.2，5.0，7.4Hz，1H，C(7)-H)ppm；
13C-NMR(100MHz，CDCl
3)δ14.1，18.8，21.9(2C)，22.7，26.5，27.5，27.9，28.1，29.3，29.49，29.53(2C)，29.6，31.9，55.4，57.0，75.7，81.2ppm；MS(ESI)m/z?301.2(M+Na
+，100％)；HRMS(ESI)calcd?for?C
19H
34NaO
+[M+Na
+]：301.2502，found：301.2504。
[0070] step 10 synthetic (-)-(7S, 8R)-7,8 epoxies-2-methyl octadecane (II)
[0071] 0～5 ℃ with nitrogen atmosphere under, (2mg, (18mg, normal hexane 0.064mmol) (1mL) solution is in 25 ℃ of reactions to add compound 6 in 10wt%) to palladium-carbon catalyst.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid II (14mg, 77%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶100)；[α]
D 20-1.0(c?1.0，CCl
4)；IR(film)v
max2951，2924，2854，1464，1378，1263，1098，1021cm
-1；
1H-NMR(400MHz，CDCl
3)δ0.84-0.91(m，9H)，1.17-1.56(m，27H)，2.84-2.96(m，2H)ppm；
13C-NMR(100MHz，CDCl
3)δ14.1，22.6，22.7，26.6，26.8，27.3，27.81，27.85，27.88，29.3，29.54，29.58，31.9，38.9，57.2ppm；MS(ESI)m/z?305.3(M+Na
+，100％)；HRMS(ESI)calcd?for?C
19H
38NaO
+[M+Na
+]：305.2815，found：305.2824。
Embodiment 2
Step 1 Synthetic 2-alkynes 13 carbon-1-alcohol (2)
-80 ℃ with argon atmospher protection down, in the ether solvent of 2-propynol (1), dropping n-Butyl Lithium (2.2M in hexane).Behind reaction 60min under-80 ℃, drip 1-bromo-decane and hexamethylphosphoramide successively, then reaction 5h under uniform temp.After unsaturated carbonate potassium solution cancellation reaction, separatory, water is used extracted with diethyl ether.The organic phase that merges is used anhydrous sodium sulfate drying, and through filtering, concentrating under reduced pressure obtains white solid 2 (82%) behind the purification by silica gel column chromatography.
Step 2 is synthesized (Z)-2-alkene 13 carbon-1-alcohol (3)
0～5 ℃ with nitrogen atmosphere under, to lindlar catalyst (Pd/BaSO
4/ Pb
2+) the middle hexane solution that adds compound 2,0～5 ℃ of reaction.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid 3 (94%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.
Step 3 synthetic (2R, 3S)-2,3-epoxy 13 carbon-1-alcohol (4)
The argon atmospher protection down; Inject exsiccant dichloromethane solvent and tetra isopropyl oxygen titanium (4.9mL to activatory
molecular sieve powder (100mg); 16.7mmol);-25 ℃ are stirred 20min down; Every afterwards separated 20min drips D-(-)-tartrate diisopropyl ester (4.2g successively; 18.0mmol) methylene dichloride (5mL) solution, (Z)-2-alkynes 13 carbon alcohol 2 (2.74g, nonane (5.5mL) solution of methylene dichloride 13.8mmol) (5mL) solution, tertbutanol peroxide (30.4mmol) is subsequently in-25 ℃ of reactions 3 days.After 40mL 10% tartaric aqueous solution cancellation reaction, slowly heat up, separatory, water is with methylene dichloride (2 * 50mL) extracted twice.(through anhydrous sodium sulfate drying, filter, and concentrating under reduced pressure obtains white solid 4 (1.80g, 61%) behind the silica gel column chromatography by 3 * 10mL) washings three times with saturated aqueous common salt for the organic layer that merges.
Step 4 synthetic (2R, 3S)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid ester (5)
Compound 4 is dissolved in the trichloromethane solvent, in-78 ℃ with argon atmospher under add pyridine and Trifluoromethanesulfonic anhydride successively, react to solution clarification ,-78 ℃ are continued about half h of reaction down.After saturated sodium carbonate solution cancellation reaction, separatory, water is used dichloromethane extraction.The organic phase that merges is used the saturated aqueous common salt washed twice, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure gets colourless liquid 5 (85%) behind the purification by silica gel column chromatography.
Step 5 synthetic (7R, 8S)-7,8 epoxies-2-methyl octadecane-4-alkynes (6)
4 methyl pentynes are dissolved in the tetrahydrofuran solvent ,-78 ℃ with argon atmospher under drip n-Butyl Lithium (2.2M in hexane).Behind-78 ℃ of reaction 10min, drip the tetrahydrofuran solution and the hexamethylphosphoramide of compound 5 successively, then reaction 1h under uniform temp.After saturated ammonium chloride solution cancellation reaction, separatory, water is used ethyl acetate extraction.The organic phase that merges is used anhydrous sodium sulfate drying, and through filtering, concentrating under reduced pressure obtains colourless liquid 6 (83%) behind the purification by silica gel column chromatography.
Step 6 synthesize (+)-(7R, 8S)-7,8 epoxies-2-methyl octadecane (I)
0～5 ℃ with nitrogen atmosphere under, to palladium-carbon catalyst (15wt%) in the adding compound 6 hexane (1mL) solution, in 25 ℃ of reactions.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid I (80%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.
Step 7 synthetic (2S, 3R)-2,3-epoxy 13 carbon-1-alcohol (7)
The argon atmospher protection down; Inject exsiccant dichloromethane solvent and tetra isopropyl oxygen titanium (5.6mL to activatory
molecular sieve powder (90mg); 18.2mmol);-25 ℃ are stirred 20min down; Every afterwards separated 20min drips L-(+)-tartrate diisopropyl ester (4.8g successively; 20.6mmol) methylene dichloride (5mL) solution, (Z)-2-alkynes 13 carbon alcohol 2 (3.14g, nonane (6.3mL) solution of methylene dichloride 15.8mmol) (5mL) solution, tertbutanol peroxide (34.9mmol) is subsequently in-25 ℃ of reactions 3 days.After 40mL 10% tartaric aqueous solution cancellation reaction, slowly heat up, separatory, water is with methylene dichloride (2 * 50mL) extracted twice.(through anhydrous sodium sulfate drying, filter, and concentrating under reduced pressure obtains white solid 7 (2.03g, 60%) behind the silica gel column chromatography by 3 * 10mL) washings three times with saturated aqueous common salt for the organic layer that merges
Step 8 synthetic (2S, 3R)-2,3-epoxy 13 carbon trifluoromethayl sulfonic acid esters (8)
Compound 7 is dissolved in the trichloromethane solvent, in-78 ℃ with argon atmospher under add pyridine and Trifluoromethanesulfonic anhydride successively, react to solution clarification ,-78 ℃ are continued about half h of reaction down.After saturated sodium carbonate solution cancellation reaction, separatory, water is used dichloromethane extraction.The organic phase that merges is used the saturated aqueous common salt washed twice, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure gets colourless liquid 8 (84%) behind the purification by silica gel column chromatography.
Step 9 synthetic (7S, 8R)-7,8 epoxies-2-methyl octadecane-4-alkynes (9)
4 methyl pentynes are dissolved in the tetrahydrofuran solvent ,-78 ℃ with argon atmospher under drip n-Butyl Lithium (2.2M in hexane).Behind-78 ℃ of reaction 10min, drip the tetrahydrofuran solution and the hexamethylphosphoramide of compound 8 successively, then reaction 1h under uniform temp.After saturated ammonium chloride solution cancellation reaction, separatory, water is used ethyl acetate extraction.The organic phase that merges is used anhydrous sodium sulfate drying, and through filtering, concentrating under reduced pressure obtains colourless liquid 9 (84%) behind the purification by silica gel column chromatography.
Step 10 synthesize (-)-(7S, 8R)-7,8 epoxies-2-methyl octadecane (II)
0～5 ℃ with nitrogen atmosphere under, to palladium-carbon catalyst (15wt%) in the adding compound 6 hexane solution, in 25 ℃ of reactions.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid II (79%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.
Embodiment 3
Step 1 Synthetic 2-alkynes 13 carbon-1-alcohol (2)
-78 ℃ with argon atmospher protection down, in the tetrahydrofuran solvent of 2-propynol (1), dropping n-Butyl Lithium (2.2M in hexane).Behind reaction 40min under-78 ℃, drip 1-bromo-decane and hexamethylphosphoramide successively, then reaction 3h under uniform temp.After saturated sodium carbonate solution cancellation reaction, separatory, water is used ethyl acetate extraction.The organic phase that merges is used anhydrous magnesium sulfate drying, and through filtering, concentrating under reduced pressure obtains white solid 2 (82%) behind the purification by silica gel column chromatography.
Step 2 is synthesized (Z)-2-alkene 13 carbon-1-alcohol (3)
0～5 ℃ with nitrogen atmosphere under, to lindlar catalyst (Pd/CaCO
3/ quinoline) hexane solution that adds compound 2 in, 0～5 ℃ of reaction.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid 3 (95%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.
Step 3 synthetic (2R, 3S)-2,3-epoxy 13 carbon-1-alcohol (4)
The argon atmospher protection down; 95mg silica gel mixing 100mg activation
molecular sieve powder; Inject exsiccant dichloromethane solvent and tetra isopropyl oxygen titanium (4.9mL; 16.7mmol);-25 ℃ are stirred 20min down, and every afterwards separated 20min drips D-(-)-tartrate diisopropyl ester (4200mg, methylene dichloride 18.0mmol) (5mL) solution, (Z)-2-alkynes 13 carbon alcohol 2 (2.74g successively; 13.8mmol) methylene dichloride (5mL) solution, nonane (5.5mL) solution of tertbutanol peroxide (30.4mmol), subsequently in-25 ℃ of reactions 3 days.After 40mL 10% tartaric aqueous solution cancellation reaction, slowly heat up, separatory, water is with methylene dichloride (2 * 50mL) extractions.(through anhydrous magnesium sulfate drying, filter, and concentrating under reduced pressure obtains white solid 4 (1.78g, 60%) behind the silica gel column chromatography by 3 * 10mL) washings three times with saturated aqueous common salt for the organic layer that merges.
Step 4 synthetic (2R, 3S)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid ester (5)
Compound 4 is dissolved in the dichloromethane solvent, in-78 ℃ with argon atmospher under add imidazoles and Trifluoromethanesulfonic anhydride successively, react to solution clarification ,-78 ℃ are continued about half h of reaction down.After saturated ammonium chloride solution cancellation reaction, separatory, water is used dichloromethane extraction.The organic phase that merges is used the saturated aqueous common salt washed twice, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure gets colourless liquid 5 (83%) behind the purification by silica gel column chromatography.
Step 5 synthetic (7R, 8S)-7,8 epoxies-2-methyl octadecane-4-alkynes (6)
4 methyl pentynes are dissolved in the ether solvent ,-78 ℃ with argon atmospher under drip n-Butyl Lithium (2.2M in hexane).Behind-78 ℃ of reaction 30min, drip the diethyl ether solution and the hexamethylphosphoramide of compound 5 successively, then reaction 2h under uniform temp.After saturated ammonium chloride solution cancellation reaction, separatory, water is used ethyl acetate extraction.The organic phase that merges is used anhydrous magnesium sulfate drying, and through filtering, concentrating under reduced pressure obtains colourless liquid 6 (84%) behind the purification by silica gel column chromatography.
Step 6 synthesize (+)-(7R, 8S)-7,8 epoxies-2-methyl octadecane (I)
0～5 ℃ with nitrogen atmosphere under, to palladium-carbon catalyst (5wt%) in the adding compound 6 hexane (1mL) solution, in 25 ℃ of reactions.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid I (79%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.
Step 7 synthetic (2S, 3R)-2,3-epoxy 13 carbon-1-alcohol (7)
The argon atmospher protection down; 95mg silica gel mixing 100mg activation
molecular sieve powder; Inject exsiccant dichloromethane solvent and tetra isopropyl oxygen titanium (5.6mL; 18.2mmol);-25 ℃ are stirred 20min down, and every afterwards separated 20min drips L-(+)-tartrate diisopropyl ester (4.8g, methylene dichloride 20.6mmol) (5mL) solution, (Z)-2-alkynes 13 carbon alcohol 2 (3.14g successively; 15.8mmol) methylene dichloride (5mL) solution, nonane (6.3mL) solution of tertbutanol peroxide (34.9mmol), subsequently in-25 ℃ of reactions 3 days.After 40mL 10% tartaric aqueous solution cancellation reaction, slowly heat up, separatory, water is with methylene dichloride (2 * 50mL) extractions.(through anhydrous magnesium sulfate drying, filter, and concentrating under reduced pressure obtains white solid 7 (2.03g, 60%) behind the silica gel column chromatography by 3 * 10mL) washings three times with saturated aqueous common salt for the organic layer that merges
Step 8 synthetic (2S, 3R)-2,3-epoxy 13 carbon trifluoromethayl sulfonic acid esters (8)
Compound 7 is dissolved in the dichloromethane solvent, in-78 ℃ with argon atmospher under add imidazoles and Trifluoromethanesulfonic anhydride successively, react to solution clarification ,-78 ℃ are continued about half h of reaction down.After saturated ammonium chloride solution cancellation reaction, separatory, water is used dichloromethane extraction.The organic phase that merges is used the saturated aqueous common salt washed twice, through anhydrous magnesium sulfate drying, filters, and concentrating under reduced pressure gets colourless liquid 8 (80%) behind the purification by silica gel column chromatography.
Step 9 synthetic (7S, 8R)-7,8 epoxies-2-methyl octadecane-4-alkynes (9)
4 methyl pentynes are dissolved in the ether solvent ,-78 ℃ with argon atmospher under drip n-Butyl Lithium (2.2M in hexane).Behind-78 ℃ of reaction 30min, drip the diethyl ether solution and the hexamethylphosphoramide of compound 8 successively, then reaction 2h under uniform temp.After saturated ammonium chloride solution cancellation reaction, separatory, water is used ethyl acetate extraction.The organic phase that merges is used anhydrous magnesium sulfate drying, and through filtering, concentrating under reduced pressure obtains colourless liquid 9 (82%) behind the purification by silica gel column chromatography.
Step 10 synthesize (-)-(7S, 8R)-7,8 epoxies-2-methyl octadecane (II)
0～5 ℃ with nitrogen atmosphere under, to palladium-carbon catalyst (5wt%) in the adding compound 6 hexane solution, in 25 ℃ of reactions.Reaction is accomplished after-filtration and is removed catalyzer, and filter cake washs with ETHYLE ACETATE, and filtrating obtains colourless liquid II (76%) through concentrating under reduced pressure behind the purification by silica gel column chromatography.
Claims (12)
1. the compound method of a gypsymoth sex pheromone is characterized in that, said gypsymoth sex pheromone is I [(+)-(7R, 8S)-7,8-epoxy-2-methyl octadecane] and enantiomorph II thereof [(-)-(7S, 8R)-7,8-epoxy-2-methyl octadecane];
The synthetic route of said gypsymoth sex pheromone is:
In following statement, specific synthetic product is according to the numbering in the structural formula, representes with Arabic numeral; R or S represent the absolute configuration of compound; + or-representing the optical direction of compound, n representes the alkyl of straight chain, OTf representes the trifluoromethayl sulfonic acid ester group.
2. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 1 is characterized in that may further comprise the steps:
1) under-80～20 ℃, compound 1 in a kind of ether solvent, under highly basic and complexing agent effect with 1-bromo-decane generation linked reaction, through extraction, dry, concentrate, obtain white solid compound 2 behind the purifying;
2) under 0～30 ℃, catalytic hydrogenation reaction takes place in compound 2 under the lindlar catalyst effect in a kind of lower boiling alkane solvent saturated by hydrogen, through filtering, concentrate, obtaining colourless liquid compound 3 behind the purifying;
3) under-40～20 ℃, Sharp's this (Sharpless) asymmetric epoxidation reaction of Lay takes place in compound 3 under catalyzer and oxygenant effect in a kind of halogenated hydrocarbon solvent, through extraction, dry, concentrate, obtain white solid compound 4 behind the purifying;
4) under-80～20 ℃, compound 4 in a kind of halohydrocarbon or ether solvent, under the organic bases effect, with the reaction of a kind of sulphonic acid anhydride, through extraction, dry, concentrate, obtain colourless liquid compound 5 behind the purifying;
5) under-80～20 ℃, compound 5 in a kind of ether solvent, under highly basic and complexing agent effect with 4-methyl pentyne generation linked reaction, through extraction, dry, concentrate, obtain colourless liquid compound 6 behind the purifying;
6) under 0～40 ℃, catalytic hydrogenation reaction takes place in compound 6 under catalyst action in a kind of lower boiling alkane solvent saturated by hydrogen, through filtration, concentrate, obtain behind the purifying colourless liquid compound (7R, 8S)-I;
7) under-40～20 ℃, Sharp's this (Sharpless) asymmetric epoxidation reaction of Lay takes place in compound 3 under catalyzer and oxygenant effect in a kind of halogenated hydrocarbon solvent, through extraction, dry, concentrate, obtain white solid compound 7 behind the purifying;
8) under-80～20 ℃, compound 7 in a kind of halohydrocarbon or ether solvent, under the organic bases effect, with the reaction of a kind of sulphonic acid anhydride, through extraction, dry, concentrate, obtain colourless liquid compound 8 behind the purifying;
9) under-80～20 ℃, compound 8 in a kind of ether solvent, under highly basic and complexing agent effect with 4-methyl pentyne generation linked reaction, through extraction, dry, concentrate, obtain colourless liquid compound 9 behind the purifying;
10) under 0～40 ℃, catalytic hydrogenation reaction takes place in compound 9 under catalyst action in a kind of lower boiling alkane solvent saturated by hydrogen, through filtration, concentrate, obtain behind the purifying colourless liquid compound (7S, 8R)-II.
3. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 1) said ether solvent is selected from C
2～C
4Aliphatic ether or alicyclic ether, particularly ether or THF; Said highly basic is n-Butyl Lithium; Said complexing agent is a hexamethylphosphoramide; Said extraction agent is selected ether for use; Said dried reagent is selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate for use; Said compound 1: highly basic: complexing agent: the mol ratio of 1-bromo-decane is 1: (2～2.5): (2～3): (1～1.5).
4. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 2) in, said lower boiling alkane solvent is selected from C
5～C
6Aliphatics saturated alkane, particularly hexanaphthene or normal hexane; Said lindlar catalyst is selected from the palladium metal that metallic lead is poisoned or quinoline is poisoned, and the lindlar catalyst carrier is lime carbonate or permanent white; Said compound 2: the massfraction of catalyzer is than being (5～20): 1.
5. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 3) said halogenated hydrocarbon solvent is selected from C
1～C
4Halohydrocarbon, particularly methylene dichloride or trichloromethane; Said catalyzer select for use tetra isopropyl oxygen titanium, D-tartrate diisopropyl ester, D-tartrate diethyl ester,
Molecular sieve,
Molecular sieve, 300～400 purpose silica gel or hydroliths; Said oxygenant is the nonane solution of anhydrous tertbutanol peroxide; Said extraction agent is selected methylene dichloride for use; Said dried reagent is selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate for use; Said compound 3: tetra isopropyl oxygen titanium: D-tartrate: the mol ratio of tertbutanol peroxide is 1: (1～1.5): (1～1.5): (2～3).
6. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 4) said halogenated hydrocarbon solvent is selected from C
1～C
4Halohydrocarbon, particularly methylene dichloride or trichloromethane; Said ether solvent is selected from C
2～C
4Aliphatic ether or alicyclic ether, particularly ether or THF; Said organic bases is selected tertiary amine for use, particularly imidazoles, pyridine or triethylamine; Said sulphonic acid anhydride is selected Trifluoromethanesulfonic anhydride for use; Said extraction agent is selected methylene dichloride for use; Said dried reagent is selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate for use; Said compound 4: organic bases: the mol ratio of sulphonic acid anhydride is 1: (3～4): (3～4).
7. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 5) said ether solvent is selected from C
2～C
4Aliphatic ether or alicyclic ether, particularly ether or THF; Said complexing agent is a hexamethylphosphoramide; Highly basic can be n-Butyl Lithium; Said extraction agent is selected ETHYLE ACETATE for use; Said dried reagent is selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate for use; Said compound 5: highly basic: complexing agent: the mol ratio of 4-methyl pentyne is 1: (2～2.5): (2～2.5): (2～2.5).
8. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 6), and said lower boiling alkane solvent is selected from C
5～C
6Aliphatics saturated alkane, particularly hexanaphthene or normal hexane, said catalyzer is the palladium charcoal; Said compound 6: the massfraction of catalyzer is than being (5～20): 1.
9. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 7) said halogenated hydrocarbon solvent is selected from C
1～C
4Halohydrocarbon, particularly methylene dichloride or trichloromethane; Said catalyzer select for use tetra isopropyl oxygen titanium, L-tartrate diisopropyl ester, L-tartrate diethyl ester,
Molecular sieve,
Molecular sieve, 300～400 purpose silica gel or hydroliths; Said oxygenant is the nonane solution of anhydrous tertbutanol peroxide; Said extraction agent is selected methylene dichloride for use; Said dried reagent is selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate for use; Said compound 3: tetra isopropyl oxygen titanium: L-tartrate: the mol ratio of tertbutanol peroxide is 1: (1～1.5): (1～1.5): (2～3).
10. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 8) said halogenated hydrocarbon solvent is selected from C
1～C
4Halohydrocarbon, particularly methylene dichloride or trichloromethane; Said ether solvent is selected from C
2～C
4Aliphatic ether or alicyclic ether, particularly ether or THF; Said organic bases is selected tertiary amine for use, particularly imidazoles, pyridine or triethylamine; Said sulphonic acid anhydride is selected Trifluoromethanesulfonic anhydride for use; Said extraction agent is selected methylene dichloride for use; Said dried reagent is selected SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate for use; Said compound 7: organic bases: the mol ratio of sulphonic acid anhydride is 1: (3～4): (3～4).
11. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 9) said ether solvent is selected from C
2～C
4Aliphatic ether or alicyclic ether, particularly ether or THF; Said complexing agent is a hexamethylphosphoramide; Highly basic is n-Butyl Lithium; Said extraction agent is selected ETHYLE ACETATE for use; Said dried reagent can be with SODIUM SULPHATE ANHYDROUS 99PCT or anhydrous magnesium sulfate; Said compound 8: highly basic: complexing agent: the mol ratio of 4-methyl pentyne is 1: (2～2.5): (2～2.5): (2～2.5).
12. the compound method of a kind of gypsymoth sex pheromone as claimed in claim 2 is characterized in that in step 10), said lower boiling alkane solvent is selected from C
5～C
6Aliphatics saturated alkane, particularly hexanaphthene or normal hexane, said catalyzer is the palladium charcoal; Said compound 9: the massfraction of catalyzer is than being (5～20): 1.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111303080A (en) * | 2020-03-12 | 2020-06-19 | 菏泽学院 | Synthesis method of gypsy moth sex pheromone |
| CN111387188A (en) * | 2020-03-03 | 2020-07-10 | 菏泽学院 | Method for preventing gypsy moth based on methyl rosinate |
| CN115353437A (en) * | 2022-08-24 | 2022-11-18 | 南京蕃茂生物科技有限公司 | Synthesis method of cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane |
| CN115490589A (en) * | 2022-07-15 | 2022-12-20 | 贵州大学 | Method for synthesizing potato tuber moth sex attractant |
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| CN101798293A (en) * | 2010-03-15 | 2010-08-11 | 厦门大学 | Simple stereoselective synthesis method of sex pheromones of hyphantria cunea |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111387188A (en) * | 2020-03-03 | 2020-07-10 | 菏泽学院 | Method for preventing gypsy moth based on methyl rosinate |
| CN111303080A (en) * | 2020-03-12 | 2020-06-19 | 菏泽学院 | Synthesis method of gypsy moth sex pheromone |
| CN115490589A (en) * | 2022-07-15 | 2022-12-20 | 贵州大学 | Method for synthesizing potato tuber moth sex attractant |
| CN115490589B (en) * | 2022-07-15 | 2024-02-09 | 贵州大学 | Synthesis method of sex attractant for potato tuber moth |
| CN115353437A (en) * | 2022-08-24 | 2022-11-18 | 南京蕃茂生物科技有限公司 | Synthesis method of cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane |
| CN115353437B (en) * | 2022-08-24 | 2024-01-12 | 南京蕃茂生物科技有限公司 | Synthesis method of cis-2-methyl-7-octadecene and cis-7, 8-epoxy-2-methyl octadecane |
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