CN102321050B - Gypsy moth sex pheromone synthesis method - Google Patents
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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 synthetic method of propylene oxide compound, especially relate to a kind of synthetic Gypsy moth sex pheromone I[(+)-(7R, 8S)-7,8-epoxy-2-methyl octadecane] and enantiomorph II[(-)-(7S, 8R)-7,8-epoxy-2-methyl octadecane] method.
Background technology
Gypsymoth has another name called 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 large, and it has the features such as feeding habits are assorted, distribution is wide, harm is heavy, larva moves with the wind.Gypsymoth occurs general in European, North America and harm is also larger, and when serious, larva can be by leaf eat everything up.Meanwhile, a large important pests for Ta Yeshi China forest, gardens, silkworm industry, fruit tree.Except northern China endangers, also there is reporting of harm on Xiamen of Fujian Province, Putian, Jiangxi and other places in recent years, produce and caused great financial loss to agroforestry.Therefore, searching effectively preventing method is very important.
Adopt the method for disparlure, not only can very effectively trap gypsymoth, reach the object that reduces 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.
The people such as Bierl (Bierl, B.A.; Beroza, M.; Collier, C.W.Science 1970,170,87) be I[(+ in 1970 from the structure that separates and identify Gypsy moth sex pheromone in female gypsymoth body)-(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 contrary, than racemic large tens times.Therefore many chemistry and biological worker are devoted to synthetic high optically pure Gypsy moth sex pheromone for many years.
Up to now, existing several different methods is applied to the synthetic of such epoxy compounds, and the main synthetic method of having reported is as follows:
1979, the K.Mori of Tokyo Univ Japan (Mori, K.; Takigawa, T.; Matsui, M.Tetrahedron 1979,35,833) set out taking natural L-(+)-tartrate as raw material, synthesize Compound I through 12 step reactions such as Wittigs (Wittig), overall yield reaches 5%.Its synthetic route is as follows:
The shortcoming of the method is that synthetic route is oversize, and productive rate is low, and atom utilization is low.It is p-methyl benzenesulfonic acid ester group that compound is write a Chinese character in simplified form OTs, i-Am
2cuLi is organic copper lithium reagent, BCl
3boron trichloride, CH
2cl
2be methylene dichloride, THP is tetrahydropyrans protecting group, i-Bu
2alH is diisobutyl aluminium hydride, n-C
8h
17pPh
3br is the phosphonium ylide reagent of octane, and n-BuLi is n-Butyl Lithium, and THF is tetrahydrofuran (THF), and Pd/C is palladium charcoal, H
2be hydrogen, TsCl is p-methyl benzene sulfonic chloride, C
5h
5n is pyridine, and TsOH is p-methyl benzenesulfonic acid, and MeOH is methyl alcohol, and KOH is potassium hydroxide.
People (Lin, the G.-Q. such as 1984 Nian Lin Guoqiang; Wu, B.-Q.; Liu, L.-Y.; Wang, X.-Q.; Zhou, W.-S.Acta Chim.Sinica (Engl.Ed.) 1984,42 (8), 797) taking (+)-glyceraldehyde acetonide as raw material, with the Grignard reagent addition of 1-bromo-decane; Nine steps such as the addition open loop of organic copper lithium reagent and epoxy are reacted, and have completed the synthetic of Compound I with 30% productive rate.Its synthetic route is as follows:
Compound write a Chinese character in simplified form n-C
10h
21mgBr is the Grignard reagent of 1-bromo-decane, and NaH is sodium hydrogen, and DMSO is methyl-sulphoxide, and BzCl is Benzoyl chloride, and HCl is hydrochloric acid, H
2o is water, and Py is pyridine, [(CH
3)
2cH (CH
2)
3]
2cuLi is organic copper lithium reagent, and HBr is hydrogen bromide, and HOAc is 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 such as addition react and synthesized Compound I, overall yield reaches 12%.Its synthetic route is as follows:
The shortcoming of the method is that synthetic route is oversize, and productive rate is low, repeatedly uses organic copper lithium reagent, and reagents ratio is more expensive, and toxicity is larger, and epoxidised stereoselectivity is bad, and the superfluous e.e. of enantiomorph only has 84%.Compound is write a Chinese character in simplified form i-Am
2cuLi is organic copper lithium reagent, and Pd is palladium, BaSO
4be barium sulfate, quinoline is quinoline, (n-C
9h
19)
2cuLi is organic copper lithium reagent.
K.Mori (Brevet, J.L. in 1992; Mori, K.Synthesis 1992,1007) taking cis-butenediol as raw material, determine the stereochemistry of epoxy compounds by the chiral separation of enzyme, afterwards by having introduced respectively the two ends side chain of Gypsy moth sex pheromone with the coupling of organic copper lithium reagent.Synthesize Compound I through ten steps with 29% productive rate, the superfluous e.e. > 99% of enantiomorph.Its synthetic route is as follows:
It is tert-butyl diphenyl chlorosilane that compound is write a Chinese character in simplified form TBDPSCl, and DMAP is DMAP, Et
3n is triethylamine, and TBAF is tetrabutyl ammonium fluoride, Et
2o is ether.
People (Marshall, the 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 raw material, has synthesized Compound I through six steps with 26% productive rate, has synthesized Compound I I through nine steps with 20% productive rate.Its synthetic route is as follows:
The shortcoming of the method is to use more malicious tin reagent, unfriendly to environment, and the superfluous e.e. of its enantiomorph also only has 90%.Compound write a Chinese character in simplified form Bu
3snLi is organotin reagent, and (S)-BINAL-H is chiral reduction agent, and TBSOTf is tertiary butyl dimethylsilyl triflate, BF
3oEt
2be etherate of trifluoroboron, Rh is rhodium, Al
2o
3be alchlor, Triton-B is benzyltrimethylammonium hydroxide.
People (Prasad, the K.R. such as K.Prasad in 2007; Anbarasan, P.J.Org.Chem.2007,72,3155) set out taking L-(+)-tartrate as raw material, built 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 ten step reactions, productive rate is 35%.Its synthetic route is as follows:
The shortcoming of the method is that step is oversize, and the reagent of using is as Grubbs 2nd catalyzer costliness very, economical not.The TBDMSOTf that writes a Chinese character in simplified form of compound is tertiary butyl dimethylsilane sulphonate, and Grubbs 2nd gen.catalyst is the catalyzer of s-generation olefin metathesis, and Bn is benzyl.
Above synthetic method mainly comprises taking optically pure natural product as starting raw material or applies some chiral catalysts, enzyme catalyst, through Multi-step conversion, could build chiral centre, synthesizes thereby complete it; But most of steps are longer, efficiency is low, economical not, sometimes also to use more malicious, to the disagreeableness reagent of environment.
Summary of the invention
Object of the present invention aims to provide a kind of taking 2-propargyl alcohol (1) cheap and easy to get as raw material, unprotect base, high-level efficiency, high enantioselectivity and high yield, the synthetic method of the easy Gypsy moth sex pheromone of synthesis technique.
Described Gypsy moth sex pheromone is I[(+)-(7R, 8S)-7,8-epoxy-2-methyl octadecane] and enantiomorph II[(-)-(7S, 8R)-7,8-epoxy-2-methyl octadecane].
The synthetic route of described Gypsy moth sex pheromone is:
In following statement, specific synthetic product is according to the numbering in structural formula, represents with Arabic numerals, and R or S represent the absolute configuration of compound ,+or-represent the optical direction of compound.N represents the alkyl of straight chain, and OTf represents trifluoromethayl sulfonic acid ester group.
The synthetic method of described Gypsy moth sex pheromone comprises the following steps:
1), at-80～20 DEG C, compound 1, in a kind of ether solvent, with 1-bromo-decane generation linked reaction, obtains white solid compound 2 under highly basic and complexing agent effect after extraction, dry, concentrated, purifying;
2) at 0～30 DEG C, in a kind of lower boiling alkane solvent saturated by hydrogen, there is catalytic hydrogenation reaction in compound 2 under lindlar catalyst effect, obtains colourless liquid compound 3 through filtering, after concentrated, purifying;
3) at-40～20 DEG C, compound 3 is in a kind of halogenated hydrocarbon solvent, under catalyzer and oxygenant effect, there is this (Sharpless) asymmetric epoxidation reaction of Sharp's Lay, after extraction, dry, concentrated, purifying, obtain white solid compound 4;
4) at-80～20 DEG C, compound 4, in a kind of halohydrocarbon or ether solvent, under organic bases effect, reacts with a kind of sulphonic acid anhydride, after extraction, dry, concentrated, purifying, obtains colourless liquid compound 5;
5), at-80～20 DEG C, compound 5, in a kind of ether solvent, with 4-methyl pentyne generation linked reaction, obtains colourless liquid compound 6 under highly basic and complexing agent effect after extraction, dry, concentrated, purifying;
6) at 0～40 DEG C, in a kind of lower boiling alkane solvent saturated by hydrogen, there is catalytic hydrogenation reaction in compound 6 under catalyst action, obtains colourless liquid compound (7R, 8S)-I through filtering, after concentrated, purifying;
7) at-40～20 DEG C, compound 3 is in a kind of halogenated hydrocarbon solvent, under catalyzer and oxygenant effect, there is this (Sharpless) asymmetric epoxidation reaction of Sharp's Lay, after extraction, dry, concentrated, purifying, obtain white solid compound 7;
8) at-80～20 DEG C, compound 7, in a kind of halohydrocarbon or ether solvent, under organic bases effect, reacts with a kind of sulphonic acid anhydride, after extraction, dry, concentrated, purifying, obtains colourless liquid compound 8;
9), at-80～20 DEG C, compound 8, in a kind of ether solvent, with 4-methyl pentyne generation linked reaction, obtains colourless liquid compound 9 under highly basic and complexing agent effect after extraction, dry, concentrated, purifying;
10) at 0～40 DEG C, in a kind of lower boiling alkane solvent saturated by hydrogen, there is catalytic hydrogenation reaction in compound 9 under catalyst action, obtains colourless liquid compound (7S, 8R)-II through filtering, after concentrated, purifying.
In step 1) in, described ether solvent can be selected from C
2～C
4aliphatic ether or alicyclic ether etc., particularly ether or tetrahydrofuran (THF) etc.; Described highly basic can be n-Butyl Lithium etc.; Described complexing agent can be hexamethylphosphoramide etc.; Described extraction agent can be selected ether etc.; Described dried reagent can be selected anhydrous sodium sulphate or anhydrous magnesium sulfate etc.; Described 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, described lower boiling alkane solvent can be selected from C
5～C
6aliphatics saturated alkane etc., particularly hexanaphthene or normal hexane etc.; Described lindlar catalyst can be selected from the palladium metal that metallic lead is poisoning or quinoline is poisoning etc., and lindlar catalyst carrier is calcium carbonate or barium sulfate etc.Described compound 2: the massfraction ratio of catalyzer can be (5～20): 1.
In step 3) in, described halogenated hydrocarbon solvent can be selected from C
1～C
4halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Described catalyzer can select tetra isopropyl oxygen titanium, D-tartrate diisopropyl ester, D-tartrate diethyl ester,
molecular sieve,
molecular sieve, 300～400 object silica gel or hydrolith etc.; Described oxygenant can be the nonane solution of anhydrous tertbutanol peroxide etc.; Described extraction agent can be selected methylene dichloride etc.; Described dried reagent can be selected anhydrous sodium sulphate or anhydrous magnesium sulfate etc.; Described 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) in, described halogenated hydrocarbon solvent can be selected from C
1～C
4halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Described ether solvent is selected from C
2～C
4aliphatic ether or alicyclic ether etc., particularly ether or tetrahydrofuran (THF) etc.; Described organic bases can be selected tertiary amine etc., particularly imidazoles, pyridine or triethylamine etc.; Described sulphonic acid anhydride can be selected Trifluoromethanesulfonic anhydride etc.; Described extraction agent can be selected methylene dichloride etc.; Described dried reagent can be selected anhydrous sodium sulphate or anhydrous magnesium sulfate etc.; Described compound 4: organic bases: the mol ratio of sulphonic acid anhydride can be 1: (3～4): (3～4).
In step 5) in, described ether solvent can be selected from C
2～C
4aliphatic ether or alicyclic ether etc., particularly ether or tetrahydrofuran (THF) etc.; Described complexing agent can be hexamethylphosphoramide etc.; Highly basic can be n-Butyl Lithium etc.; Described extraction agent can be selected ethyl acetate etc.; Described dried reagent can be selected anhydrous sodium sulphate or anhydrous magnesium sulfate etc.; Described 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) in, described lower boiling alkane solvent can be selected from C
5～C
6aliphatics saturated alkane etc., particularly hexanaphthene or normal hexane etc., described catalyzer is palladium charcoal etc.; Described compound 6: the massfraction ratio of catalyzer can be (5～20): 1.
In step 7) in, described halogenated hydrocarbon solvent can be selected from C
1～C
4halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Described catalyzer can select tetra isopropyl oxygen titanium, L-TARTARIC ACID diisopropyl ester, L-TARTARIC ACID diethyl ester,
molecular sieve,
molecular sieve, 300～400 object silica gel or hydrolith etc.; Described oxygenant can be the nonane solution of anhydrous tertbutanol peroxide etc.; Described extraction agent can be selected methylene dichloride etc.; Described dried reagent can be selected anhydrous sodium sulphate or anhydrous magnesium sulfate etc.; Described compound 3: tetra isopropyl oxygen titanium: L-TARTARIC ACID ester: the mol ratio of tertbutanol peroxide can be 1: (1～1.5): (1～1.5): (2～3).
In step 8) in, described halogenated hydrocarbon solvent can be selected from C
1～C
4halohydrocarbon etc., particularly methylene dichloride or trichloromethane etc.; Described ether solvent is selected from C
2～C
4aliphatic ether or alicyclic ether etc., particularly ether or tetrahydrofuran (THF) etc.; Described organic bases can be selected tertiary amine etc., particularly imidazoles, pyridine or triethylamine etc.; Described sulphonic acid anhydride can be selected Trifluoromethanesulfonic anhydride etc.; Described extraction agent can be selected methylene dichloride etc.; Described dried reagent can be selected anhydrous sodium sulphate or anhydrous magnesium sulfate etc.; Described compound 7: organic bases: the mol ratio of sulphonic acid anhydride can be 1: (3～4): (3～4).
In step 9) in, described ether solvent can be selected from C
2～C
4aliphatic ether or alicyclic ether etc., particularly ether or tetrahydrofuran (THF) etc.; Described complexing agent can be hexamethylphosphoramide etc.; Highly basic can be n-Butyl Lithium etc.; Described extraction agent can be selected ethyl acetate etc.; Described dried reagent can be selected anhydrous sodium sulphate or anhydrous magnesium sulfate etc.; Described 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) in, described lower boiling alkane solvent can be selected from C
5～C
6aliphatics saturated alkane etc., particularly hexanaphthene or normal hexane etc., described catalyzer is palladium charcoal etc.Described compound 9: the massfraction ratio of catalyzer can be (5～20): 1.
The present invention is taking 2-propargyl alcohol (1) cheap and easy to get as raw material, and efficient, high enantioselectivity, high productivity have synthesized Gypsy moth sex pheromone (7R, 8S)-I and enantiomorph (7S, 8R)-II thereof.Simply, productive rate is high for the each step operation of the present invention, separation, and reagent used is common agents, cheap and easy to get, and does not need to use protecting group, and route is shorter, is applicable to a large amount of production.Synthesize (7R, 8S)-I through 6 step reactions with 29% overall yield, the superfluous e.e. > 98% of enantiomorph; Synthesize (7S, 8R)-II through 6 step reactions with 27% overall yield, the superfluous e.e. > 99% of enantiomorph.
Embodiment
Below by embodiment, the present invention is further illustrated.
Embodiment 1
Step 1 is synthesized 2-alkynes 13 carbon-1-alcohol (2)
2-propargyl alcohol (1) (280mg, 5mmol) is dissolved in tetrahydrofuran (THF) (50mL) solvent, under-78 DEG C and argon atmospher, drips n-Butyl Lithium (4.7mL, 10.5mmol, 2.2Min hexane).After-78 DEG C of reaction 60min, drip successively 1-bromo-decane (11mL, 5.5mmol) and hexamethylphosphoramide (2.3mL, 13.3mmol), then react at the same temperature 5h.With after 10mL saturated sodium carbonate solution cancellation reaction, separatory, ether for water (2 × 20mL) extracting twice.The organic phase anhydrous sodium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains compound 2 (823mg, 84%) after purification by silica gel column chromatography.White solid, Mp.30-31 DEG C (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)
Under 0～5 DEG C and nitrogen atmosphere, to normal hexane (2mL) solution that adds compound 2 (30mg, 0.15mmol) in lindlar catalyst (5mg), 0～5 DEG C of reaction.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid 3 (28.5mg, 94%) after 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 is synthesized (2R, 3S)-2,3-epoxy 13 carbon-1-alcohol (4)
Under argon atmospher protection; 83mg silica gel mixing 63mg hydrolith; inject dry dichloromethane solvent and tetra isopropyl oxygen titanium (4.9mL; 16.7mmol); at-25 DEG C, stir; drip successively D-(-)-tartrate diisopropyl ester (4.2g every 20min afterwards; methylene dichloride (5mL) solution 18.0mmol), (Z)-2-alkynes 13 carbon alcohol 2 (2.74g; methylene dichloride (5mL) solution 13.8mmol), nonane (5.5mL) solution of tertbutanol peroxide (30.4mmol), subsequently in-25 DEG C of reactions 3 days.With after the tartaric aqueous solution cancellation reaction of 40mL 10%, slowly heat up, separatory, methylene dichloride for water (2 × 50mL) extracting twice.Saturated aqueous common salt for organic layer (3 × 10mL) washing merging three times, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure, obtains compound 4 (1.78g, 60%) after silica gel column chromatography.White solid, R
f0.3 (ethyl acetate: petroleum ether=1: 3); Mp.62-63 DEG C (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 is synthesized (2R, 3S)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid esters (5)
By compound 4 (250mg, 1.17mmol) be dissolved in methylene dichloride (65mL) solvent, under-78 DEG C and argon atmospher, add successively triethylamine (0.6mL, 4.21mmol) and Trifluoromethanesulfonic anhydride (0.58mL, 3.5mmol), react to solution clarification, continue reaction approximately half h at-78 DEG C.With after 5mL saturated ammonium chloride solution cancellation reaction, separatory, methylene dichloride for water (2 × 20mL) extracting twice.Saturated aqueous common salt for organic phase (2 × 5mL) washed twice merging, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure obtains colourless liquid 5 (354mg, 88%) after purification by silica gel column chromatography.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶50)。
Step 5 is synthesized (7R, 8S)-7,8 epoxies-2-methyl octadecane-4-alkynes (6)
4 methyl pentynes (0.24mL, 2.0mmol) are dissolved in ether (15mL) solvent, under-78 DEG C and argon atmospher, drip n-Butyl Lithium (0.83mL, 1.82mmol, 2.2M in hexane).After-78 DEG C of reaction 10min, drip successively diethyl ether solution (2mL) and the hexamethylphosphoramide (0.4mL, 2.3mmol) of compound 5 (350mg, 1.0mmol), then react at the same temperature 1h.With after 2mL saturated ammonium chloride solution cancellation reaction, separatory, ethyl acetate for water (3 × 10mL) extraction three times.The organic phase anhydrous sodium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains colourless liquid 6 (236mg, 85%) after 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 is synthesized (+)-(7R, 8S)-7,8 epoxies-2-methyl octadecane (I)
Under 0～5 DEG C and nitrogen atmosphere, to normal hexane (1mL) solution that adds compound 6 (57mg, 0.2mmol) in palladium-carbon catalyst (6mg, 10wt%), in 25 DEG C of reactions.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid I (47mg, 81%) after 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 is synthesized (2S, 3R)-2,3-epoxy 13 carbon-1-alcohol (7)
Under argon atmospher protection; 95mg silica gel mixing 71mg hydrolith; inject dry dichloromethane solvent and tetra isopropyl oxygen titanium (5.6mL; 18.2mmol); at-25 DEG C; drip successively L-(+)-tartrate diisopropyl ester (4.8g every 20min; methylene dichloride (5mL) solution 20.6mmol), (Z)-2-alkynes 13 carbon alcohol 2 (3.14g; methylene dichloride (5mL) solution 15.8mmol), nonane (6.3mL) solution of tertbutanol peroxide (34.9mmol), subsequently in-25 DEG C of reactions 3 days.With after the tartaric aqueous solution cancellation reaction of 40mL 10%, slowly heat up, separatory, methylene dichloride for water (2 × 50mL) extracting twice.Saturated aqueous common salt for organic layer (3 × 10mL) washing merging three times, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure, obtains compound 7 (2.06g, 61%) after silica gel column chromatography.White solid, R
f0.3 (ethyl acetate: petroleum ether=1: 3); Mp.62-63 DEG C (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 is synthesized (2S, 3R)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid esters (8)
By compound 7 (100mg, 0.47mmol) be dissolved in methylene dichloride (26mL) solvent, under-78 DEG C and argon atmospher, add successively triethylamine (0.24mL, 1.68mmol) and Trifluoromethanesulfonic anhydride (0.23mL, 1.40mmol), react to solution clarification, continue reaction approximately half h at-78 DEG C.With after 5mL saturated ammonium chloride solution cancellation reaction, separatory, methylene dichloride for water (2 × 20mL) extracting twice.Saturated aqueous common salt for organic phase (2 × 5mL) washed twice merging, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure obtains colourless liquid 8 (138mg, 85%) after purification by silica gel column chromatography.R
f?0.25(ethyl?acetate∶petroleum?ether＝1∶50)。
Step 9 is synthesized (7S, 8R)-7,8 epoxies-2-methyl octadecane-4-alkynes (9)
4 methyl pentynes (0.07mL, 0.56mmol) are dissolved in ether (3mL) solvent, under-78 DEG C and argon atmospher, drip n-Butyl Lithium (0.23mL, 0.50mmol, 2.2M in hexane).After-78 DEG C of reaction 10min, drip successively diethyl ether solution (1mL) and the hexamethylphosphoramide (0.11mL, 0.64mmol) of compound 8 (100mg, 0.28mmol), then react at the same temperature 1h.With after 1mL saturated ammonium chloride solution cancellation reaction, separatory, ethyl acetate for water (3 × 10mL) extraction three times.The organic phase anhydrous sodium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains colourless liquid 9 (66mg, 85%) after 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。
Step 10 is synthesized (-)-(7S, 8R)-7,8 epoxies-2-methyl octadecane (II)
Under 0～5 DEG C and nitrogen atmosphere, to normal hexane (1mL) solution that adds compound 6 (18mg, 0.064mmol) in palladium-carbon catalyst (2mg, 10wt%), in 25 DEG C of reactions.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid II (14mg, 77%) after 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 is synthesized 2-alkynes 13 carbon-1-alcohol (2)
Under protecting with argon atmospher at-80 DEG C, in the ether solvent of 2-propargyl alcohol (1), drip n-Butyl Lithium (2.2M in hexane).At-80 DEG C, react after 60min, drip successively 1-bromo-decane and hexamethylphosphoramide, then react at the same temperature 5h.With after unsaturated carbonate potassium solution cancellation reaction, separatory, water extracted with diethyl ether.The organic phase anhydrous sodium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains white solid 2 (82%) after purification by silica gel column chromatography.
Step 2 is synthesized (Z)-2-alkene 13 carbon-1-alcohol (3)
Under 0～5 DEG C and nitrogen atmosphere, to lindlar catalyst (Pd/BaSO
4/ Pb
2+) in add the hexane solution of compound 2,0～5 DEG C of reaction.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid 3 (94%) after purification by silica gel column chromatography.
Step 3 is synthesized (2R, 3S)-2,3-epoxy 13 carbon-1-alcohol (4)
Under argon atmospher protection, to what activate
molecular sieve powder (100mg) is injected dry dichloromethane solvent and tetra isopropyl oxygen titanium (4.9mL, 16.7mmol), at-25 DEG C, stir 20min, drip successively D-(-)-tartrate diisopropyl ester (4.2g every 20min afterwards, methylene dichloride (5mL) solution 18.0mmol), (Z)-2-alkynes 13 carbon alcohol 2 (2.74g, methylene dichloride (5mL) solution 13.8mmol), nonane (5.5mL) solution of tertbutanol peroxide (30.4mmol), subsequently in-25 DEG C of reactions 3 days.With after the tartaric aqueous solution cancellation reaction of 40mL 10%, slowly heat up, separatory, methylene dichloride for water (2 × 50mL) extracting twice.Saturated aqueous common salt for organic layer (3 × 10mL) washing merging three times, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure, obtains white solid 4 (1.80g, 61%) after silica gel column chromatography.
Step 4 is synthesized (2R, 3S)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid esters (5)
Compound 4 is dissolved in trichloromethane solvent, under-78 DEG C and argon atmospher, adds successively pyridine and Trifluoromethanesulfonic anhydride, react to solution clarification, continue reaction approximately half h at-78 DEG C.With after saturated sodium carbonate solution cancellation reaction, separatory, water dichloromethane extraction.The organic phase saturated aqueous common salt washed twice merging, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure obtains colourless liquid 5 (85%) after purification by silica gel column chromatography.
Step 5 is synthesized (7R, 8S)-7,8 epoxies-2-methyl octadecane-4-alkynes (6)
4 methyl pentynes are dissolved in tetrahydrofuran solvent, under-78 DEG C and argon atmospher, drip n-Butyl Lithium (2.2M in hexane).After-78 DEG C of reaction 10min, drip successively tetrahydrofuran solution and the hexamethylphosphoramide of compound 5, then react at the same temperature 1h.With after saturated ammonium chloride solution cancellation reaction, separatory, water is extracted with ethyl acetate.The organic phase anhydrous sodium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains colourless liquid 6 (83%) after purification by silica gel column chromatography.
Step 6 is synthesized (+)-(7R, 8S)-7,8 epoxies-2-methyl octadecane (I)
Under 0～5 DEG C and nitrogen atmosphere, to hexane (1mL) solution that adds compound 6 in palladium-carbon catalyst (15wt%), in 25 DEG C of reactions.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid I (80%) after purification by silica gel column chromatography.
Step 7 is synthesized (2S, 3R)-2,3-epoxy 13 carbon-1-alcohol (7)
Under argon atmospher protection, to what activate
molecular sieve powder (90mg) is injected dry dichloromethane solvent and tetra isopropyl oxygen titanium (5.6mL, 18.2mmol), at-25 DEG C, stir 20min, drip successively L-(+)-tartrate diisopropyl ester (4.8g every 20min afterwards, methylene dichloride (5mL) solution 20.6mmol), (Z)-2-alkynes 13 carbon alcohol 2 (3.14g, methylene dichloride (5mL) solution 15.8mmol), nonane (6.3mL) solution of tertbutanol peroxide (34.9mmol), subsequently in-25 DEG C of reactions 3 days.With after the tartaric aqueous solution cancellation reaction of 40mL 10%, slowly heat up, separatory, methylene dichloride for water (2 × 50mL) extracting twice.Saturated aqueous common salt for organic layer (3 × 10mL) washing merging three times, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure, obtains white solid 7 (2.03g, 60%) after silica gel column chromatography
Step 8 is synthesized (2S, 3R)-2,3-epoxy 13 carbon trifluoromethayl sulfonic acid esters (8)
Compound 7 is dissolved in trichloromethane solvent, under-78 DEG C and argon atmospher, adds successively pyridine and Trifluoromethanesulfonic anhydride, react to solution clarification, continue reaction approximately half h at-78 DEG C.With after saturated sodium carbonate solution cancellation reaction, separatory, water dichloromethane extraction.The organic phase saturated aqueous common salt washed twice merging, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure obtains colourless liquid 8 (84%) after purification by silica gel column chromatography.
Step 9 is synthesized (7S, 8R)-7,8 epoxies-2-methyl octadecane-4-alkynes (9)
4 methyl pentynes are dissolved in tetrahydrofuran solvent, under-78 DEG C and argon atmospher, drip n-Butyl Lithium (2.2M in hexane).After-78 DEG C of reaction 10min, drip successively tetrahydrofuran solution and the hexamethylphosphoramide of compound 8, then react at the same temperature 1h.With after saturated ammonium chloride solution cancellation reaction, separatory, water is extracted with ethyl acetate.The organic phase anhydrous sodium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains colourless liquid 9 (84%) after purification by silica gel column chromatography.
Step 10 is synthesized (-)-(7S, 8R)-7,8 epoxies-2-methyl octadecane (II)
Under 0～5 DEG C and nitrogen atmosphere, to the hexane solution that adds compound 6 in palladium-carbon catalyst (15wt%), in 25 DEG C of reactions.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid II (79%) after purification by silica gel column chromatography.
Embodiment 3
Step 1 is synthesized 2-alkynes 13 carbon-1-alcohol (2)
Under protecting with argon atmospher at-78 DEG C, in the tetrahydrofuran solvent of 2-propargyl alcohol (1), drip n-Butyl Lithium (2.2M in hexane).At-78 DEG C, react after 40min, drip successively 1-bromo-decane and hexamethylphosphoramide, then react at the same temperature 3h.With after saturated sodium carbonate solution cancellation reaction, separatory, water is extracted with ethyl acetate.The organic phase anhydrous magnesium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains white solid 2 (82%) after purification by silica gel column chromatography.
Step 2 is synthesized (Z)-2-alkene 13 carbon-1-alcohol (3)
Under 0～5 DEG C and nitrogen atmosphere, to lindlar catalyst (Pd/CaCO
3/ quinoline) in add the hexane solution of compound 2,0～5 DEG C of reaction.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid 3 (95%) after purification by silica gel column chromatography.
Step 3 is synthesized (2R, 3S)-2,3-epoxy 13 carbon-1-alcohol (4)
Under argon atmospher protection, 95mg silica gel mixing 100mg has activated
molecular sieve powder, inject dry dichloromethane solvent and tetra isopropyl oxygen titanium (4.9mL, 16.7mmol), at-25 DEG C, stir 20min, drip successively D-(-)-tartrate diisopropyl ester (4200mg every 20min afterwards, methylene dichloride (5mL) solution 18.0mmol), (Z)-2-alkynes 13 carbon alcohol 2 (2.74g, methylene dichloride (5mL) solution 13.8mmol), nonane (5.5mL) solution of tertbutanol peroxide (30.4mmol), subsequently in-25 DEG C of reactions 3 days.With after the tartaric aqueous solution cancellation reaction of 40mL 10%, slowly heat up, separatory, methylene dichloride for water (2 × 50mL) extraction.Saturated aqueous common salt for organic layer (3 × 10mL) washing merging three times, through anhydrous magnesium sulfate drying, filters, and concentrating under reduced pressure, obtains white solid 4 (1.78g, 60%) after silica gel column chromatography.
Step 4 is synthesized (2R, 3S)-2,3-epoxy 13 carbon alcohol trifluoromethayl sulfonic acid esters (5)
Compound 4 is dissolved in dichloromethane solvent, under-78 DEG C and argon atmospher, adds successively imidazoles and Trifluoromethanesulfonic anhydride, react to solution clarification, continue reaction approximately half h at-78 DEG C.With after saturated ammonium chloride solution cancellation reaction, separatory, water dichloromethane extraction.The organic phase saturated aqueous common salt washed twice merging, through anhydrous sodium sulfate drying, filters, and concentrating under reduced pressure obtains colourless liquid 5 (83%) after purification by silica gel column chromatography.
Step 5 is synthesized (7R, 8S)-7,8 epoxies-2-methyl octadecane-4-alkynes (6)
4 methyl pentynes are dissolved in ether solvent, under-78 DEG C and argon atmospher, drip n-Butyl Lithium (2.2M in hexane).After-78 DEG C of reaction 30min, drip successively diethyl ether solution and the hexamethylphosphoramide of compound 5, then react at the same temperature 2h.With after saturated ammonium chloride solution cancellation reaction, separatory, water is extracted with ethyl acetate.The organic phase anhydrous magnesium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains colourless liquid 6 (84%) after purification by silica gel column chromatography.
Step 6 is synthesized (+)-(7R, 8S)-7,8 epoxies-2-methyl octadecane (I)
Under 0～5 DEG C and nitrogen atmosphere, to hexane (1mL) solution that adds compound 6 in palladium-carbon catalyst (5wt%), in 25 DEG C of reactions.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid I (79%) after purification by silica gel column chromatography.
Step 7 is synthesized (2S, 3R)-2,3-epoxy 13 carbon-1-alcohol (7)
Under argon atmospher protection, 95mg silica gel mixing 100mg has activated
molecular sieve powder, inject dry dichloromethane solvent and tetra isopropyl oxygen titanium (5.6mL, 18.2mmol), at-25 DEG C, stir 20min, drip successively L-(+)-tartrate diisopropyl ester (4.8g every 20min afterwards, methylene dichloride (5mL) solution 20.6mmol), (Z)-2-alkynes 13 carbon alcohol 2 (3.14g, methylene dichloride (5mL) solution 15.8mmol), nonane (6.3mL) solution of tertbutanol peroxide (34.9mmol), subsequently in-25 DEG C of reactions 3 days.With after the tartaric aqueous solution cancellation reaction of 40mL 10%, slowly heat up, separatory, methylene dichloride for water (2 × 50mL) extraction.Saturated aqueous common salt for organic layer (3 × 10mL) washing merging three times, through anhydrous magnesium sulfate drying, filters, and concentrating under reduced pressure, obtains white solid 7 (2.03g, 60%) after silica gel column chromatography
Step 8 is synthesized (2S, 3R)-2,3-epoxy 13 carbon trifluoromethayl sulfonic acid esters (8)
Compound 7 is dissolved in dichloromethane solvent, under-78 DEG C and argon atmospher, adds successively imidazoles and Trifluoromethanesulfonic anhydride, react to solution clarification, continue reaction approximately half h at-78 DEG C.With after saturated ammonium chloride solution cancellation reaction, separatory, water dichloromethane extraction.The organic phase saturated aqueous common salt washed twice merging, through anhydrous magnesium sulfate drying, filters, and concentrating under reduced pressure obtains colourless liquid 8 (80%) after purification by silica gel column chromatography.
Step 9 is synthesized (7S, 8R)-7,8 epoxies-2-methyl octadecane-4-alkynes (9)
4 methyl pentynes are dissolved in ether solvent, under-78 DEG C and argon atmospher, drip n-Butyl Lithium (2.2M in hexane).After-78 DEG C of reaction 30min, drip successively diethyl ether solution and the hexamethylphosphoramide of compound 8, then react at the same temperature 2h.With after saturated ammonium chloride solution cancellation reaction, separatory, water is extracted with ethyl acetate.The organic phase anhydrous magnesium sulfate drying merging, after filtration, concentrating under reduced pressure, obtains colourless liquid 9 (82%) after purification by silica gel column chromatography.
Step 10 is synthesized (-)-(7S, 8R)-7,8 epoxies-2-methyl octadecane (II)
Under 0～5 DEG C and nitrogen atmosphere, to the hexane solution that adds compound 6 in palladium-carbon catalyst (5wt%), in 25 DEG C of reactions.After having reacted, remove by filter catalyzer, filter cake washs by ethyl acetate, and filtrate, through concentrating under reduced pressure, obtains colourless liquid II (76%) after purification by silica gel column chromatography.
Claims (6)
1. the synthetic method of a Gypsy moth sex pheromone, it is characterized in that, described Gypsy moth sex pheromone is I [(+)-(7R, 8S)-7,8-epoxy-2-methyl octadecane] and enantiomorph II [(-)-(7S, 8R)-7,8-epoxy-2-methyl octadecane];
The synthetic route of described Gypsy moth sex pheromone is:
Wherein, R or S represent the absolute configuration of compound, and+Huo – represent the optical direction of compound, and n represents the alkyl of straight chain, and OTf represents trifluoromethayl sulfonic acid ester group;
Described synthetic method comprises the following steps:
1), at-80～20 DEG C, compound 1, in a kind of ether solvent, with 1-bromo-decane generation linked reaction, obtains white solid compound 2 under highly basic and complexing agent effect after extraction, dry, concentrated, purifying; Described ether solvent is selected from C
2～C
4aliphatic ether or alicyclic ether; Described highly basic is n-Butyl Lithium; Described complexing agent is hexamethylphosphoramide; Extraction agent is selected ether; Dried reagent is selected anhydrous sodium sulphate or anhydrous magnesium sulfate; Described compound 1: highly basic: complexing agent: the mol ratio of 1-bromo-decane is 1: (2～2.5): (2～3): (1～1.5);
2) at 0～30 DEG C, in a kind of lower boiling alkane solvent saturated by hydrogen, there is catalytic hydrogenation reaction in compound 2 under lindlar catalyst effect, obtains colourless liquid compound 3 through filtering, after concentrated, purifying; Described lower boiling alkane solvent is selected from C
5～C
6aliphatics saturated alkane; Described lindlar catalyst is selected from the palladium metal that metallic lead is poisoning or quinoline is poisoning, and lindlar catalyst carrier is calcium carbonate or barium sulfate; Described compound 2: the massfraction of catalyzer is than being (5～20): 1;
3) at-40～20 DEG C, compound 3 is in a kind of halogenated hydrocarbon solvent, under catalyzer and oxygenant effect, there is this (Sharpless) asymmetric epoxidation reaction of Sharp's Lay, after extraction, dry, concentrated, purifying, obtain white solid compound 4; Described halogenated hydrocarbon solvent is selected from C
1～C
4halohydrocarbon; Described catalyzer select tetra isopropyl oxygen titanium, D-tartrate diisopropyl ester, D-tartrate diethyl ester,
molecular sieve,
molecular sieve, 300～400 object silica gel or hydroliths; Described oxygenant is the nonane solution of anhydrous tertbutanol peroxide; Extraction agent is selected methylene dichloride; Dried reagent is selected anhydrous sodium sulphate or anhydrous magnesium sulfate; Described compound 3: tetra isopropyl oxygen titanium: D-tartrate: the mol ratio of tertbutanol peroxide is 1: (1～1.5): (1～1.5): (2～3);
4) at-80～20 DEG C, compound 4, in a kind of halohydrocarbon or ether solvent, under organic bases effect, reacts with a kind of sulphonic acid anhydride, after extraction, dry, concentrated, purifying, obtains colourless liquid compound 5; Described halogenated hydrocarbon solvent is selected from C
1～C
4halohydrocarbon; Described ether solvent is selected from C
2～C
4aliphatic ether or alicyclic ether; Described organic bases is selected tertiary amine; Described sulphonic acid anhydride is selected Trifluoromethanesulfonic anhydride; Extraction agent is selected methylene dichloride; Dried reagent is selected anhydrous sodium sulphate or anhydrous magnesium sulfate; Described compound 4: organic bases: the mol ratio of sulphonic acid anhydride is 1: (3～4): (3～4);
5), at-80～20 DEG C, compound 5, in a kind of ether solvent, with 4-methyl pentyne generation linked reaction, obtains colourless liquid compound 6 under highly basic and complexing agent effect after extraction, dry, concentrated, purifying; Described ether solvent is selected from C
2～C
4aliphatic ether or alicyclic ether; Described complexing agent is hexamethylphosphoramide; Highly basic is n-Butyl Lithium; Extraction agent is selected ethyl acetate; Dried reagent is selected anhydrous sodium sulphate or anhydrous magnesium sulfate; Described compound 5: highly basic: complexing agent: the mol ratio of 4-methyl pentyne is 1: (2～2.5): (2～2.5): (2～2.5);
6) at 0～40 DEG C, in a kind of lower boiling alkane solvent saturated by hydrogen, there is catalytic hydrogenation reaction in compound 6 under catalyst action, obtains colourless liquid compound (7R, 8S)-I through filtering, after concentrated, purifying; Described lower boiling alkane solvent is selected from C
5～C
6aliphatics saturated alkane, described catalyzer is palladium charcoal; Described compound 6: the massfraction of catalyzer is than being (5～20): 1;
7) at-40～20 DEG C, compound 3 is in a kind of halogenated hydrocarbon solvent, under catalyzer and oxygenant effect, there is this (Sharpless) asymmetric epoxidation reaction of Sharp's Lay, after extraction, dry, concentrated, purifying, obtain white solid compound 7; Described halogenated hydrocarbon solvent is selected from C
1～C
4halohydrocarbon; Described catalyzer select tetra isopropyl oxygen titanium, L-TARTARIC ACID diisopropyl ester, L-TARTARIC ACID diethyl ester,
molecular sieve,
molecular sieve, 300～400 object silica gel or hydroliths; Described oxygenant is the nonane solution of anhydrous tertbutanol peroxide; Extraction agent is selected methylene dichloride; Dried reagent is selected anhydrous sodium sulphate or anhydrous magnesium sulfate; Described compound 3: tetra isopropyl oxygen titanium: L-TARTARIC ACID ester: the mol ratio of tertbutanol peroxide is 1: (1～1.5): (1～1.5): (2～3);
8) at-80～20 DEG C, compound 7, in a kind of halohydrocarbon or ether solvent, under organic bases effect, reacts with a kind of sulphonic acid anhydride, after extraction, dry, concentrated, purifying, obtains colourless liquid compound 8; Described halogenated hydrocarbon solvent is selected from C
1～C
4halohydrocarbon; Described ether solvent is selected from C
2～C
4aliphatic ether or alicyclic ether; Described organic bases is selected tertiary amine; Described sulphonic acid anhydride is selected Trifluoromethanesulfonic anhydride; Extraction agent is selected methylene dichloride; Dried reagent is selected anhydrous sodium sulphate or anhydrous magnesium sulfate; Described compound 7: organic bases: the mol ratio of sulphonic acid anhydride is 1: (3～4): (3～4);
9), at-80～20 DEG C, compound 8, in a kind of ether solvent, with 4-methyl pentyne generation linked reaction, obtains colourless liquid compound 9 under highly basic and complexing agent effect after extraction, dry, concentrated, purifying; Described ether solvent is selected from C
2～C
4aliphatic ether or alicyclic ether; Described complexing agent is hexamethylphosphoramide; Highly basic is n-Butyl Lithium; Extraction agent is selected ethyl acetate; Dried reagent is selected from anhydrous sodium sulphate or anhydrous magnesium sulfate; Described compound 8: highly basic: complexing agent: the mol ratio of 4-methyl pentyne is 1: (2～2.5): (2～2.5): (2～2.5);
10) at 0～40 DEG C, in a kind of lower boiling alkane solvent saturated by hydrogen, there is catalytic hydrogenation reaction in compound 9 under catalyst action, obtains colourless liquid compound (7S, 8R)-II through filtering, after concentrated, purifying; Described lower boiling alkane solvent is selected from C
5～C
6aliphatics saturated alkane, described catalyzer is palladium charcoal; Described compound 9: the massfraction of catalyzer is than being (5～20): 1.
2. the synthetic method of a kind of Gypsy moth sex pheromone as claimed in claim 1, is characterized in that in step 1) in, described ether solvent is selected from ether or tetrahydrofuran (THF).
3. the synthetic method of a kind of Gypsy moth sex pheromone as claimed in claim 1, is characterized in that in step 3) in, described halogenated hydrocarbon solvent is selected from methylene dichloride or trichloromethane.
4. the synthetic method of a kind of Gypsy moth sex pheromone as claimed in claim 1, is characterized in that in step 5) in, described ether solvent is selected from ether or tetrahydrofuran (THF).
5. the synthetic method of a kind of Gypsy moth sex pheromone as claimed in claim 1, is characterized in that in step 7) in, described halogenated hydrocarbon solvent is selected from methylene dichloride or trichloromethane.
6. the synthetic method of a kind of Gypsy moth sex pheromone as claimed in claim 1, is characterized in that in step 9) in, described ether solvent is selected from ether or tetrahydrofuran (THF).
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| CN115490589B (en) * | 2022-07-15 | 2024-02-09 | 贵州大学 | Synthesis method of sex attractant for potato tuber moth |
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