CN102775435B - Synthesis method of intermediate for preparing 7, 10-methoxyl docetaxel - Google Patents
Synthesis method of intermediate for preparing 7, 10-methoxyl docetaxel Download PDFInfo
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- 229960003668 docetaxel Drugs 0.000 title claims abstract description 13
- 238000001308 synthesis method Methods 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 38
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000004440 column chromatography Methods 0.000 claims description 16
- 239000012074 organic phase Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 13
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 11
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 claims description 8
- 150000001298 alcohols Chemical class 0.000 claims description 7
- 229930014667 baccatin III Natural products 0.000 claims description 4
- 238000010189 synthetic method Methods 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 abstract description 22
- 239000001257 hydrogen Substances 0.000 abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 4
- 229940123237 Taxane Drugs 0.000 abstract description 4
- 229910045601 alloy Inorganic materials 0.000 abstract description 3
- 239000000956 alloy Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 abstract 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- 229940125904 compound 1 Drugs 0.000 description 24
- 229940125782 compound 2 Drugs 0.000 description 23
- 125000006239 protecting group Chemical group 0.000 description 16
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- QXTIBZLKQPJVII-UHFFFAOYSA-N triethylsilicon Chemical group CC[Si](CC)CC QXTIBZLKQPJVII-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 230000001035 methylating effect Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 description 4
- 229960001573 cabazitaxel Drugs 0.000 description 4
- -1 dimethyl sulphide taxane compounds Chemical class 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 231100000004 severe toxicity Toxicity 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000002360 explosive Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- MJEMIOXXNCZZFK-UHFFFAOYSA-N ethylone Chemical compound CCNC(C)C(=O)C1=CC=C2OCOC2=C1 MJEMIOXXNCZZFK-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000012106 negative regulation of microtubule depolymerization Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a synthesis method of an intermediate for preparing 7, 10-methoxyl docetaxel, comprising the following steps of: with 13-site 7, 10-MeSCH2O-10-DAB protected by a silane group as an initial raw material, carrying out hydrogenation reduction with ammonium formate as a hydrogen source in the presence of an alloy to prepare 13-site 7, 10-methoxyl taxane compound protected by the silane group. The method is simple and mild in reaction conditions and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of synthetic method for the preparation of the intermediate of 7,10-methoxyl group docetaxel, belong to pharmaceutical synthesis field.
Background technology
7,10-methoxyl group docetaxel is a kind of medicine industry intermediate with using value of crucial importance, this compound may be used for the synthesis of multiple dimethyl bearing taxanes, is specially adapted to the synthesis for the treatment of late stage prostate cancer drug Cabazitaxel (Cabazitaxel).Cabazitaxel belongs to taxane anti-tumor medicament, it is another taxane anti-tumor medicament gone on the market after taxol, docetaxel, it by with tubulin binding, promote that it is assembled into microtubule, the microtubule that simultaneously these can be stoped to have assembled disintegrates, make microtubule stabilization, and then the mitotic division of T suppression cell, and the performance of Interphase cells function (interphasecellularfunctions).
Prior art discloses the preparation method of multiple 7,10-methoxyl group docetaxels, as China's application 201110293499.6 discloses a kind of 7; the preparation method of 10-methoxyl group docetaxel; comprise: (1), by compound 1 by deprotection, by 7, the hydroxyl of 10 discharges; (2) connect side chain Taxan 13, then 7,10 pairs methylate; (3) again by the side chain open loop on 13, target compound is obtained.
China's application 201110298014.2 a kind 7, the preparation method of 10-methoxyl group docetaxel, comprise the steps: step 1: in ether solvent or DMSO, DMF, DMA, after compound shown in formula II mixes with excessive mineral alkali or organic bases, carry out methylation reaction with excessive methylating reagent; Step 2: in ether solvent or DMSO, DMF, DMA, mixes above-mentioned reaction product with excessive mineral alkali or organic bases, under the effect of excessive NaH, carry out condensation reaction; Step 3: above-mentioned reaction product is hydrolyzed in acid condition, obtains target compound.
China's application 201110339593.0 discloses one with 10-deacetylate baccatin III for raw material prepares 7; the method of 10-methoxyl group docetaxel; it is first by 10-deacetylate baccatin III and chloroformic acid-2; 2; 2-trichloro ethyl ester reacts; products therefrom and DMAP, DCC and (4S; 5R)-2; 2-dimethyl-4-phenyl-3-tert-butoxycarbonyl-3; 5-oxazolidine formic acid reacts; the material obtained and acetic acid and zinc powder react, and are then methylated, finally add p-methyl benzenesulfonic acid and react and obtain target compound.
Disclose a kind of by 7 in patent CN 1270586A, 10 dimethyl sulphide taxane compounds direct-reduction under Raney's nickel, hydrogen effect obtains the preparation method of 7,10-methoxyl group taxane compounds.
10-deacetylate Bakating III prepares 7,10-methoxyl group-10-deacetylate Bakating III.
7,10-methoxyl group taxane compounds prepares 7,10-methoxyl group docetaxel (Cabazitaxel).
In patent of invention CN 102285947 A; technical scheme adopts with 10-deacetylate Bakating III as raw material; 7 are obtained by reacting at low temperatures by alkali and methyl iodide; 10-methoxyl group-10-deacetylate Bakating III; again by 7; 10-methoxyl group-10-deacetylate Bakating III obtains 7,10-methoxyl group docetaxel by methylating reagent and hydrogen reaction.Need in reaction to use the methyl iodide of severe toxicity and the defect of strong subcooling equipment, therefore, should not apply.
In view of this, special proposition the present invention.
summary of the invention:
The object of the present invention is to provide a kind of for the preparation of 7, the synthetic method of the intermediate of 10-methoxyl group docetaxel, specifically 7, the preparation method of 10-methoxyl group taxane compounds, described preparation method overcomes prior art to be needed to use the methylating reagents such as the methyl iodide of strong cryogenic refrigeration equipment and severe toxicity or methyl-sulfate and uses the shortcoming defect of highly inflammable and explosive hydrogen, compared with existing preparation method, there is required equipment simple, easy handling, and without the need to using the advantage of the methylating reagents such as hypertoxic methyl iodide or methyl-sulfate and hydrogen.
The preparation method of 7,10-methoxyl group taxane compounds provided by the invention, its synthetic route is as follows:
Wherein 13 blocking group R can be the silica-based (-Si (Et) of triethyl
3) or t-Butyldimethylsilyl (-Si (Me)
2 t-Bu).
In the present invention, the preparation method of 7,10-methoxyl group taxane compounds, carries out by the following method
7,10-dimethyl sulphide-13-siloxy-10-deacetylate Bakating III (compound 1), under the effect of alloy and ammonium formiate, is obtained by reacting 7,10-methoxyl group-13-siloxy-10-deacetylate Bakating III (compound 2) in reaction solvent.
Wherein 7,10-dimethyl sulphide-13-siloxy-10-deacetylate Bakating III (compound 1) and the mol ratio of alloy be 1:1-500, preferred 1:100.
Its interalloy is one or more in Raney's nickel RTH-2110, RTH-2124, RTH-2146, RTH-2161, RTH-3110, RTH-3124, RTH-3146, RTH-3161, RTH-4110 or RTH-5110, preferred thunder Buddhist nun RTH-3110.
Described reaction solvent is methyl alcohol, ethanol, diphenyl ether, benzene, toluene, dimethylbenzene, sym-trimethylbenzene, ethyl acetate, one or more in tert.-butyl acetate or methyl acetate, preferred alcohol.
7,10-dimethyl sulphide-13-siloxy-10-deacetylate Bakating III (compound 1) is 1:10-800 with the mol ratio of ammonium formiate, preferred 1:200; Temperature of reaction is 25 DEG C-150 DEG C, preferably 80 DEG C;
The present invention avoids using the methylating reagent (methyl-sulfate, methyl iodide) of severe toxicity and inflammable and explosive hydrogen, and various reaction conditions is and is finally determined by test, and easy gentleness, is applicable to suitability for industrialized production.
Accompanying drawing explanation
Fig. 1 is the proton nmr spectra of compound 1.
Fig. 2 is the carbon-13 nmr spectra of compound 1.
Fig. 3 is the proton nmr spectra of compound 2.
Fig. 4 is the carbon-13 nmr spectra of compound 2.
Embodiment
The following example contributes to understanding the present invention, but the present invention is not limited to the following example.
embodiment 1 (R is triethyl silicon-based protecting group, TES-)
By 7, 10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound 1) (0.95 gram, 1.2 mmol) to add in 20 milliliters of dehydrated alcohols and fully dissolve after, add Raney's nickel RTH-3110(7.04 gram, 120 mmol), add ammonium formiate (15.12 grams, 240 mmol), react airtight and be heated to 80 DEG C of reactions after 12 hours, carefully incline and reaction solution, after Raney's nickel is washed with a small amount of ethanol, merge organic phase, concentrated, column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7, 10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound 2) 0.57 gram, yield 68.9%.Wherein, the proton nmr spectra of compound 1 and compound 2 and carbon spectrum are shown in Fig. 1-Fig. 4.
1H-NMR ( 400 MHz, CDCl
3 ): 0.68 (
q,
J=8, 6H);1.02 (
t,
J=8, 9H);1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): 4.87, 6.94, 10.38, 15.23, 21.09, 22.42, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 2 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) after (0.95 gram, 1.2 mmol) to add in 20 milliliters of dehydrated alcohols and fully dissolve, add Raney's nickel RTH-2110(0.0704 gram; 1.2 mmol); add ammonium formiate (0.756 gram, 12mmol), react airtight and be heated to 25 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of ethanol, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.7 gram, yield 89.0%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.68 (
q,
J=8, 6H);1.02 (
t,
J=8, 9H);1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): 4.87, 6.94, 10.38, 15.23, 21.09, 22.42, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 3 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) after (0.95 gram, 1.2 mmol) to add in 20 milliliters of dehydrated alcohols and fully dissolve, add Raney's nickel RTH-2124(704 gram; 12000mmol); add ammonium formiate (60.48 grams, 960mmol), react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of ethanol, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.48 gram, yield 60.6%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.68 (
q,
J=8, 6H);1.02 (
t,
J=8, 9H);1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): 4.87, 6.94, 10.38, 15.23, 21.09, 22.42, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 4 (R is t-Butyldimethylsilyl protecting group, TBS-)
By 7,10-dimethyl sulphide-13-tertiary butyl dimethyl Si base-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of dehydrated alcohols and fully dissolve after; add Raney's nickel RTH-2146(7.04 gram; 120 mmol); add ammonium formiate (15.12 grams; 240 mmol); react airtight and be heated to 80 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of ethanol, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-tertiary butyl dimethyl Si base-10-deacetylate Bakating III (compound
2) 0.62 gram, yield 74.9%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 5 (R is t-Butyldimethylsilyl protecting group, TBS-)
By 7,10-dimethyl sulphide-13-tertiary butyl dimethyl Si base-10-deacetylate Bakating III (compound
1) after (0.95 gram, 1.2 mmol) to add in 20 milliliters of dehydrated alcohols and fully dissolve, add Raney's nickel RTH-2161(0.0704 gram; 1.2 mmol); add ammonium formiate (0.756 gram, 12 mmol), 25 DEG C of reactions are after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of ethanol, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-tertiary butyl dimethyl Si base-10-deacetylate Bakating III (compound
2) 0.8 gram, yield 97.0%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 6 (R is t-Butyldimethylsilyl protecting group, TBS-)
By 7,10-dimethyl sulphide-13-tertiary butyl dimethyl Si base-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of dehydrated alcohols and fully dissolve after; add Raney's nickel RTH-3124(704 gram; 12000 mmol); add ammonium formiate (60.48 grams; 960mmol); react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of ethanol, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-tertiary butyl dimethyl Si base-10-deacetylate Bakating III (compound
2) 0.45 gram, yield 54.0%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 7 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of anhydrous methanols and fully dissolve after; add Raney's nickel RTH-3146(704 gram; 12000 mmol); add ammonium formiate (60.48 grams; 960mmol); react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of anhydrous methanol, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.57 gram, yield 71.9%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 8 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of diphenyl ethers and fully dissolve after; add Raney's nickel RTH-3161(704 gram; 12000 mmol); add ammonium formiate (60.48 grams; 960mmol); react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of diphenyl ether, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.56 gram, yield 70.7%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 9 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) after (0.95 gram, 1.2 mmol) to add in 20 milliliters of benzene and fully dissolve, add Raney's nickel RTH-4110(35.2 gram; 600 mmol); add ammonium formiate (60.48 grams, 960mmol), react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of benzene, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.40 gram, yield 50.0%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 10 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) after (0.95 gram, 1.2 mmol) to add in 20 milliliters of toluene and fully dissolve, add Raney's nickel RTH-3110(704 gram; 12000 mmol); add ammonium formiate (60.48 grams, 960mmol), react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of toluene, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.53 gram, yield 66.9%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 11 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) after (0.95 gram, 1.2 mmol) to add in 20 milliliters of dimethylbenzene and fully dissolve, add Raney's nickel RTH-3110(704 gram; 12000 mmol); add ammonium formiate (60.48 grams, 960mmol), react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of dimethylbenzene, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.74 gram, yield 88.3%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 12 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of sym-trimethylbenzene and fully dissolve after; add Raney's nickel RTH-3110(704 gram; 12000 mmol); add ammonium formiate (60.48 grams; 960mmol); react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of sym-trimethylbenzene, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.40 gram, yield 50.5%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 13 (R is three second silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of ethyl acetate and fully dissolve after; add Raney's nickel RTH-3110(704 gram; 12000 mmol); add ammonium formiate (60.48 grams; 960mmol); react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of ethyl acetate, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.46 gram, yield 58.1%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 14 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of tert.-butyl acetates and fully dissolve after; add Raney's nickel RTH-3110(704 gram; 12000 mmol); add ammonium formiate (60.48 grams; 960mmol); react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of tert.-butyl acetate, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.67 gram, yield 81.0%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 15 (R is triethyl silicon-based protecting group, TES-)
By 7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound
1) (0.95 gram; 1.2 mmol) to add in 20 milliliters of methyl acetates and fully dissolve after; add Raney's nickel RTH-3110(704 gram; 12000 mmol); add ammonium formiate (60.48 grams; 960mmol); react airtight and be heated to 150 DEG C of reactions after 12 hours; carefully incline and reaction solution; after Raney's nickel is washed with a small amount of methyl acetate, merge organic phase, concentrated; column chromatography (sherwood oil: ethyl acetate=3:1) obtains 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) 0.75 gram, yield 91.0%.
1H-NMR ( 400 MHz, CDCl
3 ): 0.21 (
s, 6H); 0.92 (
s, 9H); 1.07 (
s, 3H); 1.17 (
s, 3H); 1.71 (
s,3H); 1.77 (
m, 1H); 2.11 (
s, 3H); 2.16 (
m, 2H); 2.29 (
s,3H); 2.72 (
m, 1H); 3.32 (
s, 3H); 3.46 (
s, 3H); 3.83 (
d,
J=8, 1H); 3.93 (
m, 1H); 4.14 (
d,
J=8, 1H); 4.29 (
d,
J=8, 1H); 4.84 (
s, 1H); 5.00 (
m, 2H); 5.59 (
d,
J=8, 1H); 7.47 (
m, 2H); 7.61 (
m, 1H); 8.09 (
d,
J=7.5, 2H).
13C-NMR ( 400 MHz, CDCl
3 ): -1.91, 10.38, 15.23, 21.09, 22.42, 25.91, 26.80, 31.96, 39.89, 43.08, 47.54, 56.63, 57.08, 57.39, 68.56, 75.10, 76.43, 77.23, 79.56, 80.82, 81.29, 83.16, 84.15, 128.57, 129.52, 130.05, 133.45, 133.54, 144.29, 167.05, 170.10, 205.68.
embodiment 16 (R is triethyl silicon-based protecting group, TES-)
Compared with embodiment 1; distinctive points is only; in the present embodiment 7; the mol ratio that 10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound 1) is 1:1,7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III and ammonium formiate with the mol ratio of Raney's nickel RTH-3110 is 1:10; temperature of reaction is 25 DEG C; reaction times is 6 hours, 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) yield 78.3%.
embodiment 17 (R is triethyl silicon-based protecting group, TES-)
Compared with embodiment 1; distinctive points is only; in the present embodiment 7; the mol ratio that 10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound 1) is 1:500,7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III and ammonium formiate with the mol ratio of Raney's nickel RTH-3110 is 1:800; temperature of reaction is 150 DEG C; reaction times is 20 hours, 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) yield 80.7%.
embodiment 18 (R is triethyl silicon-based protecting group, TES-)
Compared with embodiment 1; distinctive points is only; in the present embodiment 7; the mol ratio that 10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound 1) is 1:100,7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III and ammonium formiate with the mol ratio of Raney's nickel RTH-3110 is 1:200; temperature of reaction is 80 DEG C; reaction times is 12 hours, 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) yield 94.1%.
embodiment 19 (R is triethyl silicon-based protecting group, TES-)
Compared with embodiment 1; distinctive points is only; in the present embodiment 7; the mol ratio that 10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III (compound 1) is 1:250,7,10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate Bakating III and ammonium formiate with the mol ratio of Raney's nickel RTH-3110 is 1:400; temperature of reaction is 100 DEG C; reaction times is 18 hours, 7,10-methoxyl group-13-triethyl siloxy-10-deacetylate Bakating III (compound
2) yield 88.9%.
Embodiment in above-described embodiment can combine further or replace; and embodiment is only be described the preferred embodiments of the present invention; not the spirit and scope of the present invention are limited; under the prerequisite not departing from design philosophy of the present invention; the various changes and modifications that in this area, professional and technical personnel makes technical scheme of the present invention, all belong to protection scope of the present invention.
Claims (1)
1. one kind for the preparation of 7, the synthetic method of the intermediate of 10-methoxyl group docetaxel, it is characterized in that: by 1.2 mmol 7, after 10-dimethyl sulphide-13-triethyl siloxy-10-deacetylate baccatin III to add in 20 milliliters of dehydrated alcohols and fully dissolves, add 120 mmol Raney's nickel RTH-3110, add 240 mmol ammonium formiates, react airtight and be heated to 80 DEG C of reactions after 12 hours, carefully incline and reaction solution, after Raney's nickel is washed with a small amount of ethanol, merge organic phase, concentrated, column chromatography obtains 7, 10-methoxyl group-13-triethyl siloxy-10-deacetylate baccatin III.
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|---|---|---|---|---|
| EP0694539A1 (en) * | 1994-07-28 | 1996-01-31 | Bristol-Myers Squibb Company | 7-o-Ethers of taxane derivatives |
| CN1179776A (en) * | 1995-03-27 | 1998-04-22 | 罗纳-布朗克罗莱尔股份有限公司 | Novel taxoids, preparation thereof and pharmaceutical compositions containing same |
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|---|---|---|---|---|
| EP0694539A1 (en) * | 1994-07-28 | 1996-01-31 | Bristol-Myers Squibb Company | 7-o-Ethers of taxane derivatives |
| CN1179776A (en) * | 1995-03-27 | 1998-04-22 | 罗纳-布朗克罗莱尔股份有限公司 | Novel taxoids, preparation thereof and pharmaceutical compositions containing same |
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