CN105348242B - Natural products () (6S, 2 ' R) cryptocaryalactone synthetic method - Google Patents
Natural products () (6S, 2 ' R) cryptocaryalactone synthetic method Download PDFInfo
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 12
- 229930014626 natural product Natural products 0.000 title claims abstract description 10
- YRJUGPYWWJLWEW-UHFFFAOYSA-N Cryptocaryalactone Natural products CC(=O)OC(CC=CC1CC=CC(=O)O1)c2ccccc2 YRJUGPYWWJLWEW-UHFFFAOYSA-N 0.000 title abstract description 11
- TYMKVQRXYUDCIH-ZHACJKMWSA-N [(e)-1-(6-oxo-2,3-dihydropyran-2-yl)-4-phenylbut-3-en-2-yl] acetate Chemical compound C=1C=CC=CC=1/C=C/C(OC(=O)C)CC1CC=CC(=O)O1 TYMKVQRXYUDCIH-ZHACJKMWSA-N 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 79
- 238000006243 chemical reaction Methods 0.000 claims abstract description 58
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 20
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 10
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims abstract description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 6
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims abstract description 5
- 229930016911 cinnamic acid Natural products 0.000 claims abstract description 5
- 235000013985 cinnamic acid Nutrition 0.000 claims abstract description 5
- 150000002148 esters Chemical group 0.000 claims abstract description 5
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 5
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 230000007062 hydrolysis Effects 0.000 claims abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 3
- 239000000463 material Substances 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 87
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 60
- 239000000243 solution Substances 0.000 claims description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 24
- 238000001035 drying Methods 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 17
- 239000003208 petroleum Substances 0.000 claims description 17
- 238000004440 column chromatography Methods 0.000 claims description 15
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 claims description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- 239000003480 eluent Substances 0.000 claims description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 12
- 239000012074 organic phase Substances 0.000 claims description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 12
- 239000011780 sodium chloride Substances 0.000 claims description 12
- 238000001514 detection method Methods 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
- 229910003074 TiCl4 Inorganic materials 0.000 claims description 10
- 150000001299 aldehydes Chemical class 0.000 claims description 9
- 239000012264 purified product Substances 0.000 claims description 9
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 7
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 238000006555 catalytic reaction Methods 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 150000003222 pyridines Chemical class 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 5
- 229940125898 compound 5 Drugs 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 150000002460 imidazoles Chemical class 0.000 claims description 5
- -1 silyl enol ethers Chemical class 0.000 claims description 5
- OZGSEIVTQLXWRO-UHFFFAOYSA-N 2,4,6-trichlorobenzoyl chloride Chemical class ClC(=O)C1=C(Cl)C=C(Cl)C=C1Cl OZGSEIVTQLXWRO-UHFFFAOYSA-N 0.000 claims description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- 238000006632 Weinreb amidation reaction Methods 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229940126214 compound 3 Drugs 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 4
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical class CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 claims description 3
- 238000010790 dilution Methods 0.000 claims description 3
- 239000012895 dilution Substances 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 239000010410 layer Substances 0.000 claims description 3
- 239000012044 organic layer Substances 0.000 claims description 3
- VZOPRCCTKLAGPN-UHFFFAOYSA-L potassium;sodium;2,3-dihydroxybutanedioate;tetrahydrate Chemical class O.O.O.O.[Na+].[K+].[O-]C(=O)C(O)C(O)C([O-])=O VZOPRCCTKLAGPN-UHFFFAOYSA-L 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 230000004044 response Effects 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- ZFDIRQKJPRINOQ-HWKANZROSA-N Ethyl crotonate Chemical compound CCOC(=O)\C=C\C ZFDIRQKJPRINOQ-HWKANZROSA-N 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 2
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 claims description 2
- 150000002085 enols Chemical class 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 claims description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 claims description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 239000010703 silicon Substances 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-N trans-cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-N 0.000 claims description 2
- ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims 6
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 2
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 235000019270 ammonium chloride Nutrition 0.000 claims 1
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims 1
- 238000010828 elution Methods 0.000 claims 1
- 238000003810 ethyl acetate extraction Methods 0.000 claims 1
- 238000006206 glycosylation reaction Methods 0.000 claims 1
- 239000003921 oil Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 125000000422 delta-lactone group Chemical group 0.000 abstract description 3
- 230000000397 acetylating effect Effects 0.000 abstract description 2
- 238000011017 operating method Methods 0.000 abstract description 2
- 239000002243 precursor Substances 0.000 abstract description 2
- 238000003799 Mukaiyama Aldol addition reaction Methods 0.000 abstract 1
- 230000000977 initiatory effect Effects 0.000 abstract 1
- 230000008859 change Effects 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- 244000080208 Canella winterana Species 0.000 description 1
- 235000008499 Canella winterana Nutrition 0.000 description 1
- 241001081178 Cryptocarya Species 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- VPCAAUUIFCAFRZ-UHFFFAOYSA-N butylalumane Chemical compound CCCC[AlH2] VPCAAUUIFCAFRZ-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of synthetic method of mono- isomers of natural products Cryptocaryalactone.It is initiation material by cinnamic acid cheap and easy to get, reacted by Evans adol, upper protection group, DIBAL H are reduced, the processes such as Mukaiyama Aldol reactions complete the synthesis to key intermediate formula 7, then through hydrolysis, Yanaguchi ester ring closure reactions obtain the precursor compound 8 of natural products, finally take off the protection of Bn bases, it is acetylating to complete the fully synthetic of target molecule formula 9 synthetic routes modern design in high yield rationally, raw material is cheap and easy to get, operating procedure is easy, reaction condition is gentle, efficiently complete with α, () (6S of β unsaturation δ lactone structures, 2'R) cryptocaryalactone's is fully synthetic, the advantages that product configuration is single.
Description
Technical field
The present invention relates to a kind of synthetic method of mono- isomers of natural products Cryptocaryalactone, belong to organic
Chemosynthesis technical field.
Background technology
Natural products Cryptocaryalactones belongs to dihydropyran ketone compound, and (-)-(6S, 2'R)-
Cryptocaryalactone (compound of formula 9) was Cryptocarya by Spencer et al. in 1984 from one kind
What moschata canella extracted, its final contour structures is the method for passing through asymmetric syntheses by H.H.Meye
Determine.Cryptocaryalactone is natural Germination suppression agent but does not have inhibitory action to corn.From (-)-(6S, 2'
R)-cryptocaryalactone structure is seen, it has a α, the molecular skeleton of the undersaturated δ lactones of β, a styryl
Side chain, also two different chiral centres.The structure of the undersaturated δ lactones of this α, β has extensive bioactivity (such as right
Cancer cell plays cytotoxin effect) because it can be used as Michael acceptors, so as to cause numerous synthesis chemists, life
Thing scholar and the great interest of pharmacologist.The structural formula of compound of formula 9 is：
At present, on its enantiomter (+)-(6S, 2'R)-cryptocaryalactone and diastereoisomer
(-)-(6S, 2'S)-epi cryptocaryalactone synthesis report has a lot, such as Gowravaram Sabitha etc.
People has been delivered on (+)-(6S, 2'R)-cryptocaryalactone and (-)-(6S, 2' in 2008 on Tetrahedron
S) the fully synthetic article of-epi cryptocaryalactone stereoselectivities；Palakodety Radha Krishna et al.
In 2009 Journal of Organic Chemistry delivered one with RCM react to obtain (+)-(6S, 2'R)-
Cryptocaryalactone article；Dinesh C.Bhunia et al. were also sent out in 2012 in Tetrahedron Letters
One related article of table, but for directly synthesis (-)-(6S, 2'R)-cryptocaryalactone report article also
No.The highway route design and method for the synthesis of natural product Cryptocaryalactones that contrast has been reported are carefully analyzed, mostly
It is to be used as key step with RCM reactions, the structure on chiral centre is then using the routine operation for quoting chiral source, synthesizes road
Line is all long, and some reactions are how many that speed is slow, yield is low, side reaction is more, racemization etc. easily occurs for chiral centre
Problem.
The content of the invention
Synthetic method provided by the invention is intended to using cinnamic acid cheap and easy to get as raw material, reacts structure by Evans adol
Build first chiral centre, Weinreb amidation process, upper Bn bases protection group, DIBAL-H reduction, Mukaiyama Aldol are anti-
Second chiral centre should be built, then builds hexa-atomic lactonic ring, last acetyl group through hydrolysis, Yanaguchi esters ring closure reaction
Replacementization Bn bases in high yield complete the fully synthetic of target molecule.The design of whole route is unique novel, and its course of reaction is anti-
Mild condition is answered, speed is fast, easy to operate, and raw material is cheap and easy to get, can substantially reduce synthesis cost.It is against compounding design following formula：
What the synthesis of the compound of target molecule formula 9 was realized in：Using cinnamic acid as raw material, and chiral auxiliary is through Evans
Adol reacts to obtain the compound 3 of single configuration；Then through Weinreb amidation process, under the conditions of the NaH on Bn bases protect
Compound 5, is then reduced through DIBAL-H, and silyl enol ether carries out Mukaiyama Aldol and reacted to be closed under lewis acid
Key intermediate 7；Finally hydrolyzed under lithium hydroxide, Yanaguchi occurs under 2,4,6- trichloro-benzoyl chlorides and pyridine catalysis
Ester ring closure reaction, acetyl group replacementization Bn bases obtain target molecule 9 i.e. natural products (-)-(6S, 2'R)-
Cryptocaryalactone, synthetic route such as following formula：
Specifically：
A kind of new method of synthesis of natural product (-)-compound of (6S, 2'R)-cryptocaryalactone formulas 9 is as follows
Formula, the compound of formula 8 is first in Lu Xisi acid TiCl4Under the conditions of take off Bn base protection groups, then pyridine, DMAP effect under with Ac2O
Generation acylation reaction obtains the compound of formula 9,
For another example following formula, the compound of formula 7 obtain corresponding acid through lithium hydrate, then in 2,4,6- trichloro-benzoyl chlorides
Under being catalyzed with pyridine, using DCM as solvent, Yanaguchi reactions occur at room temperature, constructs hexa-atomic lactonic ring, obtains the formula 8
Compound,
For another example following formula, the synthesis of the compound of formula 7 pass through Mukaiyama Aldol by the compound of formula 5 and the compound of formula 6
Reaction obtains, and constructs second chiral centre,
For another example following formula, the compound of formula 6 is raw material by cheap and easily-available ethyl crotonate, using THF as solvent, with i-
Pr2NH, n-BuLi and DMPU are catalyst, are reacted in a low temperature of -78 DEG C with TMSCl,
For another example following formula, the DMF solution of the compound of 5 formula of formula 4 is under NaH catalysis and benzyl bromine BnBr is -20
Reaction obtains at DEG C,
For another example following formula, the compound of 4 formula of formula 3 is under imidazoles effect, using DCM as solvent, with N, O- diformazans
Base hydroxylammonium salts hydrochlorate reacts to obtain,
For another example following formula, it is raw material with trans cinnamic acid 1, using DCM as solvent, in TiCl4, DIPEA catalysis it is lower with it is chiral
Evans adol occur under -78 DEG C of cryogenic conditions and react to obtain the compound of formula 3 for auxiliary agent 2, construct first chirality
Center,
More specifically：
Under nitrogen protection, the compound of chiral auxiliary formula 2 (2.4g, 9.57mmol) is dissolved in dichloromethane DCM (20mL),
0 DEG C is cooled to, is slowly added TiCl4(1.15ml)；After stirring 10min at 0 DEG C, diisopropyl ethyl amine is slowly added to
DIPEA (1.82ml), stir 10min；Reaction system is moved on at -78 DEG C, is added dropwise the two of aldehyde 1 (1.15g, 8.7mmol)
Chloromethanes solution (5mL), stirs 1.5h at low temperature；Treat to add 1.5ml saturations NH after the completion of TLC detection reactions4Cl solution is quenched,
Room temperature is moved to, waits solution system to be extracted after being raised to room temperature with DCM (30ml × 3), merges organic phase, then with saturation NaCl solution
Washing, anhydrous sodium sulfate drying, filtering, purified product (ethyl acetate is used column chromatography after concentration：Petroleum ether=1:5), most
Eluent is concentrated to give the compound of yellow, viscous formula 3 afterwards.
At room temperature, under nitrogen protection, the compound of formula 3 (2.9g, 7.57mmol) is dissolved in 37.8ml DCM, first added
2.58g imidazoles, N, O- dimethyl hydroxyl ammonium salt hydrochlorate MeONHMeHCl (1.48g, 15.14mmol) is added afterwards, reaction is overnight；
Add saturation NH4Cl solution is quenched, and is extracted with DCM (40ml × 3), anhydrous sodium sulfate drying, filtering, through pillar layer separation after concentration
(ethyl acetate：Petroleum ether=1:2) eluent, is concentrated to give the compound of white crystal formula 4.
Under nitrogen protection, the compound (444mg, 1.9mmol) of inclining of Weinreb acid amides 4 is dissolved in 6mL DMF, be placed in-
20 DEG C, 152mg 60% NaH is added, BnBr (0.56mL) is then added dropwise, stirs 30min at this temperature；TLC is examined
Survey and add 2ml saturations NH after the completion of reacting4Cl solution is quenched, and moves to room temperature, adds water (20ml × 3) to extract, is done with anhydrous sodium sulfate
It is dry, filtering, through column chromatography for separation (ethyl acetate after concentration：Petroleum ether=1:5) eluent, is concentrated to give into yellow oily formula 5 to change
Compound.
The compound of formula 5 (0.73g, 2.26mmol) is dissolved in refined DCM 18mL, -78 DEG C is cooled to, it is different to be added dropwise two
Butyl aluminum hydride DIBAL-H (4.5mL, 6.78mmol, 1.5M in toluene), reacts 20min at low temperature, and TLC detections are anti-
After the completion of answering, add 5mL methanol to be quenched, reaction system be warming up to room temperature, add 10mL sodium potassium tartrate tetrahydrates, 2h is stirred at room temperature,
Washed with 1N HCl (2.5mL), merge organic layer, with anhydrous sodium sulfate drying, filtered, the crude product of corresponding aldehyde is obtained after concentration,
Directly cast single step reaction；Under nitrogen protection, by homemade 1M Ti (o-ipr)2Cl2(3.5ml) is dissolved in 11ml toluene, puts
Enter in -78 DEG C of low temperature, then the unpurified aldehyde for having been dissolved in 4.5ml toluene is added dropwise, 10min is stirred at -78 DEG C；
Silyl enol ether 6 (1.2g, 6.78mmol) is dissolved in 2.7ml toluene, then is added dropwise in reaction system, is stirred at -78 DEG C
1h. reactions terminate plus 5ml saturations NaHCO3Reaction is quenched in solution, is extracted with DCM (25ml × 3), merges organic phase, uses saturation
NaCl solution is washed, anhydrous sodium sulfate drying, filtering, purified product (ethyl acetate is used column chromatography after concentration：Petroleum ether=
1:10) eluent finally, is concentrated to give the faint yellow compound of oily formula 7.
The compound of formula 7 (314mg, 0.86mmol) is dissolved into 12ml THF, then adds 6ml methanol；By 412mg hydrogen-oxygens
Change lithium to be dissolved in 6ml water, be added to dropper in reaction bulb, react 3h at room temperature；After TLC detection display reactions completely, add 1M
PH value is adjusted to 6 by HCl, is then extracted with ethyl acetate (25ml × 3), is merged organic phase, anhydrous sodium sulfate drying, is filtered, dense
Yellow oily compound is obtained after contracting；Under nitrogen protection, obtained yellow oily compound is dissolved in DCM (0.2mL), at 0 DEG C
Under 0.2ml (2,4,6)-trichloro-benzoyl chloride and 2mL pyridines is slowly added dropwise, rise again to room temperature reaction 1h.Reaction terminates plus saturation
NaHCO3Reaction is quenched in solution, is extracted with DCM (5ml × 3), merges organic phase, is washed with saturation NaCl solution, anhydrous sodium sulfate
Dry, filtering, purified product (ethyl acetate is used column chromatography after concentration：Petroleum ether=1:10), finally eluent is concentrated
Obtain the compound of formula 8.
The compound of formula 8 (86mg, 0.26mmol) is dissolved in DCM (2.6mL), 0 DEG C is cooled to, is slowly added into TiCl4
(0.029g, 0.26mmol), after 30min plus saturation NaHCO3Reaction is quenched in solution, is filtered with diatomite, DCM (5ml × 3) extractions
Take, anhydrous sodium sulfate drying, filter, concentration；Under nitrogen protection plus 1.3ml DCM, 0.025ml pyridines and DMAP are then added
(cat.), acetic anhydride Ac is added at 0 DEG C2O (0.03ml), about 1h is reacted, question response adds methylene chloride dilution after terminating, and uses saturation
NaHCO3Solution and saturation NaCl solution are washed respectively, then with anhydrous sodium sulfate drying, are filtered, concentration, then divided with column chromatography
From purification (ethyl acetate：Petroleum ether=1:2) it is the compound of final product formula 9 to obtain white solid.
This synthetic route mentality of designing novel and unique, it is most prominent the characteristics of be to complete day with more succinct synthetic route
Right product (-)-(6S, 2'R)-cryptocaryalactone's is fully synthetic, reacts structure set forth herein selection with Evans adol
Cryptocaryalactone first chiral centre is built, is closed in the Mukaiyama aldol of the benzyl induction methods reacted
The compound of key intermediate compound formula 7 is taken into second chiral centre, and is constructed by reactions such as Yanaguchi cyclizations
δ lactonic rings are the compound of precursor compound formula 8, and the method is so far there are no document report.The present invention is raw material by cinnamic acid, warp
Cross Evans adol to react, Weinreb amidation process, upper Bn bases protection group, DIBAL-H reduction, Mukaiyama Aldol are anti-
Answer, Yanaguchi ester ring closure reactions, Deprotection, acetylating reaction completes the fully synthetic of target molecule formula 9, the synthesis
Highway route design has new reasonable, and raw material is cheap and easy to get, and operating procedure is easy, and reaction condition is gentle, and it is excellent that product configuration is single etc.
Point.
Embodiment
In order that the present invention is more clearly understood, below in conjunction with example, the present invention will be described in further detail.Should
Understand, instantiation described herein only to explain the present invention, is not intended to limit the present invention.
Embodiment 1:The synthesis of the compound of formula 3
Under nitrogen protection, chiral auxiliary 2 (2.4g, 9.57mmol) is dissolved in dichloromethane DCM (20mL), is cooled to 0
DEG C, it is slowly added TiCl4(1.15ml).After stirring 10min at 0 DEG C, diisopropyl ethyl amine DIPEA is slowly added to
(1.82ml), stir 10min.Reaction system is moved on at -78 DEG C, aldehyde 1 (1.15g, 8.7mmol) dichloromethane is added dropwise
Solution (5mL), stirs 1.5h at low temperature.Treat to add 1.5ml saturations NH after the completion of TLC detection reactions4Cl solution is quenched, and moves to room
Temperature, wait solution system to be extracted after being raised to room temperature with DCM (30ml × 3), merge organic phase, then washed with saturation NaCl solution,
Anhydrous sodium sulfate drying, filtering, uses column chromatography purified product (ethyl acetate after concentration：Petroleum ether=1:5), will finally wash
De- liquid is concentrated to give yellow, viscous compound 3 (3.03g, 91%).
Embodiment 2:The synthesis of the compound of formula 4
At room temperature, under nitrogen protection, compound 3 (2.9g, 7.57mmol) is dissolved in 37.8ml DCM, first added
2.58g imidazoles, N, O- dimethyl hydroxyl ammonium salt hydrochlorate MeONHMeHCl (1.48g, 15.14mmol) is added afterwards, reaction is overnight.
Add saturation NH4Cl solution is quenched, and is extracted with DCM (40ml × 3), anhydrous sodium sulfate drying, filtering, through pillar layer separation after concentration
(ethyl acetate：Petroleum ether=1:2) eluent, is concentrated to give white crystalline Compound 4 (1.68g, 94%).
Embodiment 3:The synthesis of the compound of formula 5
Under nitrogen protection, Weinreb acid amides 4 (444mg, 1.9mmol) is dissolved in 6mL DMF, is placed in -20 DEG C, adds
Enter 152mg 60% NaH, BnBr (0.56mL) is then added dropwise, stirs 30min at this temperature.TLC detection reactions
After the completion of plus 2ml saturations NH4Cl solution is quenched, and moves to room temperature, adds water (20ml × 3) to extract, with anhydrous sodium sulfate drying, mistake
Filter, through column chromatography for separation (ethyl acetate after concentration：Petroleum ether=1:5) eluent, is concentrated to give yellow oily compound 5
(495mg, 80%).
Embodiment 4:The synthesis of the compound of formula 7
Synthesis compound 7 first reduces compound 5, and concrete operations are as follows：Compound 5 (0.73g, 2.26mmol) is molten
In refined DCM 18mL, -78 DEG C are cooled to, diisobutyl aluminium hydride DIBAL-H (4.5mL, 6.78mmol, 1.5M is added dropwise
In toluene), 20min is reacted at low temperature, after the completion of TLC detection reactions, adds 5mL methanol to be quenched, reaction system is heated up
To room temperature, add 10mL sodium potassium tartrate tetrahydrates, 2h is stirred at room temperature, washed with 1N HCl (2.5mL), merge organic layer, use is anhydrous
Sodium sulphate is dried, and filtering, the crude product of corresponding aldehyde is obtained after concentration, directly casts single step reaction.
Under nitrogen protection, by homemade 1M Ti (o-ipr)2Cl2(3.5ml) is dissolved in 11ml toluene, is put into -78 DEG C
In low temperature, then the unpurified aldehyde for having been dissolved in 4.5ml toluene is added dropwise, 10min is stirred at -78 DEG C.By enol silicon
Ether 6 (1.2g, 6.78mmol) is dissolved in 2.7ml toluene, then is added dropwise in reaction system, and 1h. reaction knots are stirred at -78 DEG C
Beam adds 5ml saturations NaHCO3Reaction is quenched in solution, is extracted with DCM (25ml × 3), merges organic phase, is washed with saturation NaCl solution
Wash, anhydrous sodium sulfate drying, filter, purified product (ethyl acetate is used column chromatography after concentration：Petroleum ether=1:10), finally
Eluent is concentrated to give faint yellow oily compound 7 (538mg, 65%).
Embodiment 5:The synthesis of the compound of formula 8
The compound of formula 7 (314mg, 0.86mmol) is dissolved into 12ml THF, then adds 6ml methanol；By 412mg hydrogen-oxygens
Change lithium to be dissolved in 6ml water, be added to dropper in reaction bulb, react 3h at room temperature.After TLC detection display reactions completely, add 1M
PH value is adjusted to 6 by HCl, is then extracted with ethyl acetate (25ml × 3), is merged organic phase, anhydrous sodium sulfate drying, is filtered, dense
It is standby that yellow oily compound is obtained after contracting.
Under nitrogen protection, compound obtained above is dissolved in DCM (0.2mL), be slowly added dropwise at 0 DEG C 0.2ml (2,
4,6)-trichloro-benzoyl chloride and 2mL pyridines, rise again to room temperature reaction 1h.Reaction terminates plus saturation NaHCO3Reaction is quenched in solution,
Extracted with DCM (5ml × 3), merge organic phase, washed with saturation NaCl solution, anhydrous sodium sulfate drying, filtered, used after concentration
Column chromatography for separation purified product (ethyl acetate：Petroleum ether=1:10) eluent finally, is concentrated to give yellow oily compound 8
(158mg, 55%).
Embodiment 6:The synthesis of the compound of formula 9
Compound 8 (86mg, 0.26mmol) is dissolved in DCM (2.6mL), 0 DEG C is cooled to, is slowly added into TiCl4
(0.029g, 0.26mmol), after 30min plus saturation NaHCO3Reaction is quenched in solution, is filtered with diatomite, DCM (5ml × 3) extractions
Take, anhydrous sodium sulfate drying, filter, concentration.Under nitrogen protection plus 1.3ml DCM, 0.025ml pyridines and DMAP are then added
(cat.), acetic anhydride Ac is added at 0 DEG C2O (0.03ml), about 1h is reacted, question response adds methylene chloride dilution after terminating, and uses saturation
NaHCO3Solution and saturation NaCl solution are washed respectively, then with anhydrous sodium sulfate drying, are filtered, concentration, then divided with column chromatography
From purification (ethyl acetate：Petroleum ether=1:2) it is final product 9 (59mg, 80%) to obtain white solid.
The foregoing is only presently preferred embodiments of the present invention, be not intended to limit the invention, it is all the present invention spirit and
All any modification, equivalent and improvement made within principle etc., should be included in the scope of the protection.
Claims (8)
1. a kind of method of synthesis of natural product (-)-compound of (6S, 2'R)-cryptocaryalactone formulas 9, its feature exist
In such as following formula, using cinnamic acid as raw material, and chiral auxiliary reacts to obtain the compound 3 of single configuration through Evans adol；Then
Through Weinreb amidation process, under the conditions of the NaH on Bn bases protect to obtain compound 5, then reduced through DIBAL-H, and enol silicon
Ether carries out Mukaiyama Aldol under lewis acid and reacts to obtain key intermediate 7；Finally under lithium hydroxide hydrolysis,
2,4,6- trichloro-benzoyl chlorides and the lower generation Yanaguchi esters ring closure reaction of pyridine catalysis, acetyl group replacementization Bn bases obtain mesh
The compound of molecule 9 is marked,
2. the synthetic method of the compound of formula 9 according to claim 1, it is characterised in that with trans cinnamic acid 1 for original
Material, using DCM as solvent, with Evansadol occurs under cryogenic conditions of the chiral auxiliary 2 at -78 DEG C under TiCl4, DIPEA catalysis
Reaction obtains the compound of formula 3, constructs first chiral centre；The compound of formula 3 is under imidazoles effect, using DCM as solvent,
With N, O- dimethyl hydroxyl ammonium salt hydrochlorates react to obtain the compound of formula 4；By the DMF solution of the compound of formula 4 under NaH catalysis
Reacted with benzyl bromine BnBr at -20 DEG C and obtain the compound of formula 5；It is raw material by cheap and easily-available ethyl crotonate, using THF to be molten
Agent, with i-Pr2NH, n-BuLi and DMPU for catalyst, reacted in a low temperature of -78 DEG C with TMSCl the compound of formula 6, formula 7 are changed
The synthesis of compound is reacted to obtain by the compound of formula 5 and the compound of formula 6 by Mukaiyama Aldol, constructs second chirality
Center；The compound of formula 7 obtains corresponding acid through lithium hydrate, is then catalyzed in 2,4,6- trichloro-benzoyl chlorides and pyridine
Under, using DCM as solvent, Yanaguchi reactions occur at room temperature, constructs hexa-atomic lactonic ring, obtains the compound of formula 8；Formula 8
Compound first takes off Bn base protection groups under the conditions of Lu Xisi acid TiCl4, and acyl then occurs with Ac2O under pyridine, DMAP effects
Glycosylation reaction obtains the compound of final product formula 9.
3. the synthetic method of the compound of formula 9 according to claim 2, it is characterised in that：Under nitrogen protection, by 2.4g,
The compound of 9.57mmol chiral auxiliaries formula 2 is dissolved in 20mL dichloromethane DCM, is cooled to 0 DEG C, is slowly added 1.15ml
TiCl4；After stirring 10min at 0 DEG C, diisopropyl ethyl amine 1.82ml DIPEA are slowly added to, stir 10min；Will reaction
System is moved on at -78 DEG C, is added dropwise containing 1.15g, the 5mL dichloromethane solutions of 8.7mmol aldehyde 1, is stirred at low temperature
1.5h；Treat to add 1.5ml saturations NH after the completion of TLC detection reactions4Cl solution is quenched, and moves to room temperature, waits solution system to be raised to room temperature
Use DCM, each 30ml to extract afterwards 3 times, merge organic phase, then washed with saturation NaCl solution, anhydrous sodium sulfate drying, mistake
Filter, purified product is used column chromatography after concentration, mobile phase is ethyl acetate and petroleum ether, and the two volume ratio is 1:5, finally will
Eluent is concentrated to give the compound of yellow, viscous formula 3.
4. the synthetic method of the compound of formula 9 according to claim 3, it is characterised in that：At room temperature, under nitrogen protection,
By 2.9g, the compound of 7.57mmol formulas 3 is dissolved in 37.8ml DCM, first adds 2.58g imidazoles, adds 1.48g, 15.14mmol afterwards
N, O- dimethyl hydroxyl ammonium salt hydrochlorate MeONHMeHCl, reaction is overnight；Add saturation NH4Cl solution to be quenched, extracted with DCM, often
Secondary 40ml, extract 3 times, anhydrous sodium sulfate drying, filtering, through pillar layer separation after concentration, mobile phase is ethyl acetate and oil
Ether, the two volume ratio are 1:2, eluent is concentrated to give the compound of white crystal formula 4.
5. the synthetic method of the compound of formula 9 according to claim 4, it is characterised in that：Under nitrogen protection, by 444mg,
The compound of 1.9mmol Weinreb acid amides 4 is dissolved in 6mL DMF, is placed in -20 DEG C, adds 152mg 60% NaH, then by
0.56mL BnBr are added dropwise to, stir 30min at this temperature；Add 2ml saturations NH after the completion of TLC detection reactions4Cl solution is quenched
Go out, move to room temperature, add water to extract, each 20ml, extract 3 times, with anhydrous sodium sulfate drying, filtering, through column chromatography point after concentration
From mobile phase is ethyl acetate and petroleum ether, and the two volume ratio is 1:5, eluent is concentrated to give the compound of yellow oily formula 5.
6. the synthetic method of the compound of formula 9 according to claim 5, it is characterised in that：By 0.73g, 2.26mmol formulas 5 are changed
Compound is dissolved in refined DCM 18mL, is cooled to -78 DEG C, and 4.5mL, 6.78mmol diisobutyl aluminium hydrides is added dropwise, and specification is
1.5M toluene solution, 20min is reacted at low temperature, after the completion of TLC detection reactions, adds 5mL methanol to be quenched, by reaction system liter
Temperature arrives room temperature, adds 10mL sodium potassium tartrate tetrahydrates, 2h is stirred at room temperature, washed with 2.5mL1N HCl, merges organic layer, and use is anhydrous
Sodium sulphate is dried, and filtering, the crude product of corresponding aldehyde is obtained after concentration, directly casts single step reaction；Under nitrogen protection, will be homemade
3.5ml 1M Ti (o-ipr) 2Cl2 is dissolved in 11ml toluene, is put into -78 DEG C of low temperature, then will have been dissolved in 4.5ml toluene
Unpurified aldehyde is added dropwise, and 10min is stirred at -78 DEG C；By 1.2g, 6.78mmol silyl enol ethers 6 are dissolved in 2.7ml toluene,
It is added dropwise to again in reaction system, 1h. reactions is stirred at -78 DEG C and terminate to add 5ml saturations NaHCO3Reaction is quenched in solution, uses
DCM is extracted, each 25ml, is extracted 3 times, is merged organic phase, is washed with saturation NaCl solution, anhydrous sodium sulfate drying, is filtered, dense
Purified product is used column chromatography after contracting, mobile phase is ethyl acetate and petroleum ether, and the two volume ratio is 1:10, finally will elution
Liquid is concentrated to give the faint yellow compound of oily formula 7.
7. the synthetic method of the compound of formula 9 according to claim 6, it is characterised in that：The chemical combination of 314mg, 0.86mmol formula 7
Thing is dissolved into 12ml THF, then adds 6ml methanol；412mg lithium hydroxides are dissolved in 6ml water, reaction is added to dropper
In bottle, 3h is reacted at room temperature；After TLC detection display reactions completely, add 1M HCl that pH value is adjusted into 6, then use ethyl acetate
Extraction, each 25ml are extracted 3 times, are merged organic phase, anhydrous sodium sulfate drying, filtering, yellow oily compound are obtained after concentration；
Under nitrogen protection, obtained yellow oily compound is dissolved in 0.2mL DCM, 0.2ml (2,4,6)-three is slowly added dropwise at 0 DEG C
Chlorobenzoyl chloride and 2mL pyridines, rise again to room temperature reaction 1h；Reaction terminates plus reaction is quenched in saturation NaHCO3 solution, is extracted with DCM
Take, each 5ml is extracted 3 times, is merged organic phase, is washed with saturation NaCl solution, anhydrous sodium sulfate drying, is filtered, is used after concentration
Column chromatography for separation purified product, mobile phase are ethyl acetate and petroleum ether, and the two volume ratio is 1:10, finally eluent is concentrated
Obtain the compound of formula 8.
8. the synthetic method of the compound of formula 9 according to claim 7, it is characterised in that：By 86mg, 0.26mmol formulas 8 are changed
Compound is dissolved in 2.6mL DCM, is cooled to 0 DEG C, is slowly added into 0.029g, 0.26mmol TiCl4, after 30min plus saturation NaHCO3
Reaction is quenched in solution, is filtered with diatomite, and DCM extractions, each 5ml is extracted 3 times, anhydrous sodium sulfate drying, is filtered, concentration；
Nitrogen protection is lower to add 1.3ml DCM, then adds 0.025ml pyridines and DMAP, adds acetic anhydride 0.03ml Ac2O at 0 DEG C, instead
Should about 1h, question response adds methylene chloride dilution after terminating, with saturation NaHCO3Solution and saturation NaCl solution are washed respectively, then
With anhydrous sodium sulfate drying, filter, concentration, then use column chromatography purification, mobile phase is ethyl acetate and petroleum ether, the two body
Product is than being 1:2, obtain the white solid i.e. compound of final product formula 9.
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| ABSOLUTE CONFIGURATIONS OF ALL FOUR STEREOISOMERS OF CRYPTOCARYALACTONE AND DEACETYL CRYPTOCARYALACTONE;SIEGFRIED E. DREWES et al.;《Phytochemistry》;19980630;第49卷(第6期);1683-1687 * |
| Stereoselective total synthesis of (-)-(6R,2S)-cryptocaryalactone and (-)-(6S,20S)-epi cryptocaryalactone via asymmetric acetate aldol reaction;J. S. Yadav et al.;《Tetrahedron Letters》;20120305;第53卷;2496-3499 * |
| Total Synthesis of (þ)-Cryptocaryalactone and of a Diastereoisomer of (þ)-Strictifolione via Ring-Closing Metathesis (RCM) and Olefin Cross-Metathesis (CM);Gowravaram Sabitha et al.;《Helvetica Chimica Acta》;20101231;第93卷;329-338 * |
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