【结 构 式】 |
【药物名称】Treprostinil sodium, Uniprost, LRX-15, U-62840, UT-15, BW-15AU, 15AU81, Remodulin 【化学名称】9-Deoxy-3,7-(1',3'-interphenylene)-2',9-methano-3-oxa-4,5,6-trinor-13,14-dihydroprostaglandin F1 sodium salt 【CA登记号】289480-64-4, 81846-19-7 (free acid) 【 分 子 式 】C23H33NaO5 【 分 子 量 】412.50626 |
【开发单位】United Therapeutics (Orphan Drug), Pfizer (Originator), GlaxoSmithKline (Not Determined), Ferrer (Licensee), Paladin (Licensee), United Therapeutics (Licensee), Gentiva (Distributor), Priority Healthcare (Distributor) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Peripheral Vascular Disease, Treatment of, Pulmonary Hypertension, Treatment of, Prostacyclin Analogs |
合成路线1
The reaction of the prostaglandin E1 derivative (I) with N,S-dimethylphenylsulfonimide (II) by means of methylmagnesium chloride in THF gives intermediate (III), which is treated with aluminum amalgam in HOAc/water to yield the methylene derivative (IV). Hydroboration of (IV) with 9-borabicyclo[3.3.1]nonane (9-BBN) in THF affords the hydroxymethyl derivative (V), which is treated with methanesulfonyl chloride and TEA in dichloromethane to provide mesylate (VI). Desilylation of compound (VI) with TBAF in THF gives the phenol derivative (VII), which is cyclized by means of NaH in THF yielding the tricyclic prostaglandin derivative (VIII). Alkylation of compound (VIII) with methyl bromoacetate (IX) by means of NaH in glyme affords the 2-hydroxyacetate derivative (X), which is treated first with HOAc/water in order to eliminate the THP protecting groups, and then with KOH in methanol/water to hydrolyze the methyl ester group providing the prostaglandin F1 derivative (XI). Finally, this compound is hydrogenated over Pd/C in ethyl acetate.
【1】 Sorbera, L.A.; Castaner, J.; Rabasseda, X.; UT-15. Drugs Fut 2001, 26, 4, 364. |
【2】 Aristoff, P.A.; Kelly, R.C.; Nelson, N.A. (Pharmacia Corp.); Carbacyclin analogues. CH 648017; CH 655308; FR 2484413; GB 2070596; JP 1990167248; JP 1994145085 . |
【3】 Aristoff, P.A. (Pharmacia Corp.); Methano carbacyclin analogs. US 4349689 . |
【4】 Agoh, Y.; Agoh, M.; Tamura, T.; Kuriyama, H.; Soga, M.; Mori, T. (Maruishi Pharmaceutical Co., Ltd.); 1,2-Disubstd. 1,4-dihydro-4-oxoquinoline cpds.. EP 1081138; JP 2001064259; JP 2001064261; JP 2001089455; JP 2001089476 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 46549 | (2R,3R,4R)-2-(3-[[tert-butyl(dimethyl)silyl]oxy]benzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentanone | C36H58O6Si | 详情 | 详情 | |
(II) | 46550 | methyl(methylimino)oxo(phenyl)-lambda(6)-sulfane | C8H11NOS | 详情 | 详情 | |
(III) | 46551 | tert-butyl(dimethyl)[3-([(1R,2R,3R)-5-[[methyl(phenyl)sulfonimidoyl]methyl]-3-(tetrahydro-2H-pyran-2-yloxy)-2-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl)phenoxy]silane | C44H69NO6SSi | 详情 | 详情 | |
(IV) | 46552 | tert-butyl(dimethyl)silyl 3-([(1R,2R,3R)-5-methylene-3-(tetrahydro-2H-pyran-2-yloxy)-2-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl)phenyl ether; tert-butyl(dimethyl)[3-([(1R,2R,3R)-5-methylene-3-(tetrahydro-2H-pyran-2-yloxy)-2-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl)phenoxy]silane | C37H60O5Si | 详情 | 详情 | |
(V) | 46553 | [(1S,2S,3S,4R)-2-(3-[[tert-butyl(dimethyl)silyl]oxy]benzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methanol | C37H62O6Si | 详情 | 详情 | |
(VI) | 46554 | [(1S,2S,3S,4R)-2-(3-[[tert-butyl(dimethyl)silyl]oxy]benzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl methanesulfonate | C38H64O8SSi | 详情 | 详情 | |
(VII) | 46555 | [(1S,2S,3S,4R)-2-(3-hydroxybenzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl methanesulfonate | C32H50O8S | 详情 | 详情 | |
(VIII) | 46556 | (1S,2R,3aS,9aS)-2-(tetrahydro-2H-pyran-2-yloxy)-1-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-ol | C31H46O5 | 详情 | 详情 | |
(IX) | 12309 | methyl 2-bromoacetate; methyl bromoacetate | 96-32-2 | C3H5BrO2 | 详情 | 详情 |
(X) | 46507 | 3-bromo-6-phenyl-2-pyrazinecarbonitrile | C11H6BrN3 | 详情 | 详情 | |
(XI) | 46508 | 1-[(E)-2-phenylethenyl]pyrrolidine | C12H15N | 详情 | 详情 |
合成路线2
The reduction of 2-octyn-1-ol (XII) with bis(2-methoxyethoxy)aluminum hydride in toluene/THF gives 2-octen-1-ol (XIII), which is treated with tert-butyl hydroperoxide, (+)-diethyl L-tartrate and titanium tetraisopropoxide in dichloromethane yielding epoxide (XIV). The latter is reduced with bis(2-ethoxyethoxy)aluminum hydride in toluene/THF, affording the chiral diol (XV). The selective monotosylation of (XV) with TsCl in pyridine provides the primary tosylate (XVI), which is treated with NaI in hot acetone to furnish 1-iodo-3-octanol (XVII). Protection of (XVII) with dihydropyran and pyridine hydrochloride gives the tetrahydropyranyl ether (XVIII), which is condensed with dimethyl methylphosphonate (XIX) by means of BuLi and TEA in THF to yield the phosphonate (XX). Condensation of compound (XX) with 5-methoxy-2,3,3a,4-tetrahydronaphtho[2,3-b]furan-2-one (XXI) by means of BuLi in THF affords the tricyclic adduct (XXII), which is hydrogenated with H2 over Pd/C in ethanol to provide compound (XXIII). Isomerization of (XXIII) with NaOH in refluxing ethanol gives diastereomer (XXIV). The reduction of the carbonyl group of (XXIV) with NaBH4 in methanol, followed by deprotection with HOAc in THF yields compound (XXV). The demethylation of compound (XXV) by means of BuLi and Ph2PH in THF affords the tricyclic phenol (XXVI), which is condensed with 2-chloroacetonitrile (XXVII) by means of K2CO3 in refluxing acetone to provide the precursor (XXVIII). Finally, the cyano group of (XXVIII) is hydrolyzed with KOH in refluxing water.
【1】 Sorbera, L.A.; Castaner, J.; Rabasseda, X.; UT-15. Drugs Fut 2001, 26, 4, 364. |
【2】 Aristoff, P.A. (Pharmacia Corp.); Carbacyclin analogues. EP 0159784; JP 1985208936; US 4683330 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XII) | 46559 | 2-octyn-1-ol | C8H14O | 详情 | 详情 | |
(XIII) | 46560 | (E)-2-octen-1-ol | C8H16O | 详情 | 详情 | |
(XIV) | 46561 | [(2R,3S)-3-pentyloxiranyl]methanol | C8H16O2 | 详情 | 详情 | |
(XV) | 46562 | (3S)-1,3-octanediol | C8H18O2 | 详情 | 详情 | |
(XVI) | 46563 | (3S)-3-hydroxyoctyl 4-methylbenzenesulfonate | C15H24O4S | 详情 | 详情 | |
(XVII) | 46564 | (3S)-1-iodo-3-octanol | C8H17IO | 详情 | 详情 | |
(XVIII) | 46565 | (1S)-1-(2-iodoethyl)hexyl tetrahydro-2H-pyran-2-yl ether; 2-[[(1S)-1-(2-iodoethyl)hexyl]oxy]tetrahydro-2H-pyran | C13H25IO2 | 详情 | 详情 | |
(XIX) | 13067 | ethyl 5,6-difluoro-8-oxo-3H,8H-4-oxa-1-thia-9b-azacyclopenta[cd]phenalene-9-carboxylate | C15H9F2NO4S | 详情 | 详情 | |
(XX) | 46566 | dimethyl (4S)-4-(tetrahydro-2H-pyran-2-yloxy)nonylphosphonate | C16H33O5P | 详情 | 详情 | |
(XXI) | 46567 | (3aS)-5-methoxy-3a,4-dihydronaphtho[2,3-b]furan-2(3H)-one | C13H12O3 | 详情 | 详情 | |
(XXII) | 46568 | (9aS)-8-methoxy-3-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,4,9,9a-tetrahydro-2H-cyclopenta[b]naphthalen-2-one | C27H38O4 | 详情 | 详情 | |
(XXIII) | 46569 | (1S,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,3,3a,4,9,9a-hexahydro-2H-cyclopenta[b]naphthalen-2-one | C27H40O4 | 详情 | 详情 | |
(XXIV) | 46570 | (1R,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,3,3a,4,9,9a-hexahydro-2H-cyclopenta[b]naphthalen-2-one | C27H40O4 | 详情 | 详情 | |
(XXV) | 46571 | (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C22H34O3 | 详情 | 详情 | |
(XXVI) | 46572 | (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalene-2,5-diol | C21H32O3 | 详情 | 详情 | |
(XXVII) | 14443 | 2-chloroacetonitrile; chloroacetonitrile | 107-14-2 | C2H2ClN | 详情 | 详情 |
(XXVIII) | 46573 | 2-([(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl]oxy)acetonitrile | C23H33NO3 | 详情 | 详情 |
合成路线3
Reaction of 3-methoxybenzyl alcohol (XXIX) with TBDMS-Cl and imidazole in dichloromethane gives the silyl ether (XXX), which is condensed with allyl bromide (XXXI) by means of BuLi in hexane to yield the 2-allyl derivative (XXXII). Deprotection of (XXXII) by means of TBAF in THF affords the benzyl alcohol (XXXIII), which is oxidized with oxalyl chloride and TEA in DMSO/dichloromethane to provide 2-allyl-3-methoxybenzaldehyde (XXXIV). Condensation of compound (XXXIV) with the chiral 1-decyne (XXXV) by means of ethylmagnesium bromide in THF gives the secondary alcohol (XXXVI), which is oxidized with pyridinium chlorochromate (PCC) in dichloromethane yielding ketone (XXXVII). The enantioselective reduction of ketone (XXXVII) by means of trimethylboroxine (TMBO), BH3/Me2S and (R)-(2-pyrrolidinyl)diphenylmethanol in toluene affords the chiral secondary alcohol (XXXVIII) as a single diastereomer. Silylation of alcohol (XXXVIII) with TBDMS-Cl and imidazole yields the corresponding ether (XXXIX), which is submitted to cyclization catalyzed by Co2(CO)8 in refluxing acetonitrile affording the tricyclic ketone (XL). Hydrogenation of the conjugated double bond of (XL) with H2 over Pd/C in ethanol provides the saturated ketone (XLI), which is reduced with NaBH4 in ethanol to give the tricyclic alcohol (XLII). Elimination of the tetrahydropyranyl-protecting group of (XLII) with p-toluensulfonic acid in methanol provides diol (XXV) already described.
【1】 Sorbera, L.A.; Castaner, J.; Rabasseda, X.; UT-15. Drugs Fut 2001, 26, 4, 364. |
【2】 Rao, M.S.; Staszewski, J.P.; Guo, L.; Penmasta, R.; Moriarty, R.M. (United Therapeutics Corp.); Process for stereoselective synthesis of prostacyclin derivs.. WO 9921830 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
20632 | diphenyl[(2R)pyrrolidinyl]methanol | C17H19NO | 详情 | 详情 | ||
(XXV) | 46571 | (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C22H34O3 | 详情 | 详情 | |
(XXIX) | 46574 | 3-Anisylalcohol; (3-methoxyphenyl)methanol; m-Anisyl alcohol; m-methoxybenzyl alcohol; 3-Anisic alcohol; 3-Anise Alcohol; 3-methoxybenzyl alcohol; 3-methoxybenzene methanol | 6971-51-3 | C8H10O2 | 详情 | 详情 |
(XXX) | 46575 | tert-butyl(dimethyl)silyl 3-methoxybenzyl ether; tert-butyl[(3-methoxybenzyl)oxy]dimethylsilane | C14H24O2Si | 详情 | 详情 | |
(XXXI) | 11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
(XXXII) | 46576 | 2-allyl-3-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl methyl ether; [(2-allyl-3-methoxybenzyl)oxy](tert-butyl)dimethylsilane | C17H28O2Si | 详情 | 详情 | |
(XXXIII) | 46577 | (2-allyl-3-methoxyphenyl)methanol | C11H14O2 | 详情 | 详情 | |
(XXXIV) | 46578 | 2-allyl-3-methoxybenzaldehyde | C11H12O2 | 详情 | 详情 | |
(XXXV) | 46579 | (1S)-1-pentyl-4-pentynyl tetrahydro-2H-pyran-2-yl ether; 2-[[(1S)-1-pentyl-4-pentynyl]oxy]tetrahydro-2H-pyran | C15H26O2 | 详情 | 详情 | |
(XXXVI) | 46580 | (6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-ol | C26H38O4 | 详情 | 详情 | |
(XXXVII) | 46581 | (6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-one | C26H36O4 | 详情 | 详情 | |
(XXXVIII) | 46582 | (1S,6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-ol | C26H38O4 | 详情 | 详情 | |
(XXXIX) | 46583 | [[(1S,6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecynyl]oxy](tert-butyl)dimethylsilane; 2-allyl-3-[(1S,6S)-1-[[tert-butyl(dimethyl)silyl]oxy]-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecynyl]phenyl methyl ether | C32H52O4Si | 详情 | 详情 | |
(XL) | 46584 | (4R,9aS)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-methoxy-3-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,4,9,9a-tetrahydro-2H-cyclopenta[b]naphthalen-2-one | C33H52O5Si | 详情 | 详情 | |
(XLI) | 46570 | (1R,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,3,3a,4,9,9a-hexahydro-2H-cyclopenta[b]naphthalen-2-one | C27H40O4 | 详情 | 详情 | |
(XLII) | 46585 | (1R,2R,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C27H42O4 | 详情 | 详情 |
合成路线4
【1】 Aristoff PA. 1987. Interphenylene carbacyclin derivatives. US 4683330(本专利属于The Upjohn Compa- ny) Aristoff PA 1981.Composition and pro卧US 4306075(本专利■于The Upjohn Company) Aristoff PA. 1982,Methno carbacyclin analogs US 4349689(本专利属于The Upjohn Company) |
【2】 Aristoff PA. 1981.Composition and process. US 4306075(本专利属于The Upjohn Company) |
【3】 Aristoff PA. 1982. Methno carbacyclin analogs. US 4349689(本专利属于The Upjohn Company) |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 14647 | 5-methoxy-3,4-dihydro-2(1H)-naphthalenone | 32940-15-1 | C11H12O2 | 详情 | 详情 |
(II) | 46567 | (3aS)-5-methoxy-3a,4-dihydronaphtho[2,3-b]furan-2(3H)-one | C13H12O3 | 详情 | 详情 | |
(III) | 46566 | dimethyl (4S)-4-(tetrahydro-2H-pyran-2-yloxy)nonylphosphonate | C16H33O5P | 详情 | 详情 | |
(IV) | 46568 | (9aS)-8-methoxy-3-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,4,9,9a-tetrahydro-2H-cyclopenta[b]naphthalen-2-one | C27H38O4 | 详情 | 详情 | |
(VI) | 46549 | (2R,3R,4R)-2-(3-[[tert-butyl(dimethyl)silyl]oxy]benzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentanone | C36H58O6Si | 详情 | 详情 | |
(VII) | 66890 | 2-(3-((tert-butyldimethylsilyl)oxy)benzyl)-1-((N-methylphenylsulfonimidoyl)methyl)-4-((tetrahydro-2H-pyran-2-yl)peroxy)-3-(3-((tetrahydro-2H-pyran-2-yl)peroxy)octyl)cyclopentanol | C44H71NO9SSi | 详情 | 详情 | |
(VIII) | 46555 | [(1S,2S,3S,4R)-2-(3-hydroxybenzyl)-4-(tetrahydro-2H-pyran-2-yloxy)-3-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]cyclopentyl]methyl methanesulfonate | C32H50O8S | 详情 | 详情 | |
(IX) | 46556 | (1S,2R,3aS,9aS)-2-(tetrahydro-2H-pyran-2-yloxy)-1-[(E,3S)-3-(tetrahydro-2H-pyran-2-yloxy)-1-octenyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-ol | C31H46O5 | 详情 | 详情 |
合成路线5
【1】 Moriarty RM, Rani N, Enache LA, et aL. 2004. The intramolecular asymmetric pauson-khand cyclization as a novel and general stereoselective route to benzindene prostaclrclins: synthesis of UT-15(Treprostinil). J Org Chcm, 69 (6): 1890~1902 |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 46574 | 3-Anisylalcohol; (3-methoxyphenyl)methanol; m-Anisyl alcohol; m-methoxybenzyl alcohol; 3-Anisic alcohol; 3-Anise Alcohol; 3-methoxybenzyl alcohol; 3-methoxybenzene methanol | 6971-51-3 | C8H10O2 | 详情 | 详情 |
(II) | 46575 | tert-butyl(dimethyl)silyl 3-methoxybenzyl ether; tert-butyl[(3-methoxybenzyl)oxy]dimethylsilane | C14H24O2Si | 详情 | 详情 | |
(III) | 46576 | 2-allyl-3-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl methyl ether; [(2-allyl-3-methoxybenzyl)oxy](tert-butyl)dimethylsilane | C17H28O2Si | 详情 | 详情 | |
(IV) | 46577 | (2-allyl-3-methoxyphenyl)methanol | C11H14O2 | 详情 | 详情 | |
(V) | 46578 | 2-allyl-3-methoxybenzaldehyde | C11H12O2 | 详情 | 详情 | |
(VI) | 46579 | (1S)-1-pentyl-4-pentynyl tetrahydro-2H-pyran-2-yl ether; 2-[[(1S)-1-pentyl-4-pentynyl]oxy]tetrahydro-2H-pyran | C15H26O2 | 详情 | 详情 | |
(VII) | 46580 | (6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-ol | C26H38O4 | 详情 | 详情 | |
(VIII) | 46581 | (6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-one | C26H36O4 | 详情 | 详情 | |
(IX) | 46582 | (1S,6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-ol | C26H38O4 | 详情 | 详情 | |
(X) | 46583 | [[(1S,6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecynyl]oxy](tert-butyl)dimethylsilane; 2-allyl-3-[(1S,6S)-1-[[tert-butyl(dimethyl)silyl]oxy]-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecynyl]phenyl methyl ether | C32H52O4Si | 详情 | 详情 | |
(XI) | 46584 | (4R,9aS)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-methoxy-3-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,4,9,9a-tetrahydro-2H-cyclopenta[b]naphthalen-2-one | C33H52O5Si | 详情 | 详情 | |
(XII) | 46570 | (1R,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,3,3a,4,9,9a-hexahydro-2H-cyclopenta[b]naphthalen-2-one | C27H40O4 | 详情 | 详情 | |
(XIII) | 46585 | (1R,2R,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C27H42O4 | 详情 | 详情 | |
(XIV) | 46571 | (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C22H34O3 | 详情 | 详情 | |
(XV) | 46572 | (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalene-2,5-diol | C21H32O3 | 详情 | 详情 | |
(XVI) | 46573 | 2-([(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl]oxy)acetonitrile | C23H33NO3 | 详情 | 详情 |
合成路线6
【1】 Moriarty RM, Penmasta R. Guo L et al. 2002. Process for stereoselective synthesis of prostacyclin derivatives. US 6441245(本专利属于United Thenpeutics Corporation, USA) |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II) | 46575 | tert-butyl(dimethyl)silyl 3-methoxybenzyl ether; tert-butyl[(3-methoxybenzyl)oxy]dimethylsilane | C14H24O2Si | 详情 | 详情 | |
(I) | 46574 | 3-Anisylalcohol; (3-methoxyphenyl)methanol; m-Anisyl alcohol; m-methoxybenzyl alcohol; 3-Anisic alcohol; 3-Anise Alcohol; 3-methoxybenzyl alcohol; 3-methoxybenzene methanol | 6971-51-3 | C8H10O2 | 详情 | 详情 |
(III) | 46576 | 2-allyl-3-([[tert-butyl(dimethyl)silyl]oxy]methyl)phenyl methyl ether; [(2-allyl-3-methoxybenzyl)oxy](tert-butyl)dimethylsilane | C17H28O2Si | 详情 | 详情 | |
(IV) | 46577 | (2-allyl-3-methoxyphenyl)methanol | C11H14O2 | 详情 | 详情 | |
(V) | 46578 | 2-allyl-3-methoxybenzaldehyde | C11H12O2 | 详情 | 详情 | |
(VI) | 46579 | (1S)-1-pentyl-4-pentynyl tetrahydro-2H-pyran-2-yl ether; 2-[[(1S)-1-pentyl-4-pentynyl]oxy]tetrahydro-2H-pyran | C15H26O2 | 详情 | 详情 | |
(VII) | 46580 | (6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-ol | C26H38O4 | 详情 | 详情 | |
(VIII) | 46581 | (6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-one | C26H36O4 | 详情 | 详情 | |
(IX) | 46582 | (1S,6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecyn-1-ol | C26H38O4 | 详情 | 详情 | |
(X) | 46583 | [[(1S,6S)-1-(2-allyl-3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecynyl]oxy](tert-butyl)dimethylsilane; 2-allyl-3-[(1S,6S)-1-[[tert-butyl(dimethyl)silyl]oxy]-6-(tetrahydro-2H-pyran-2-yloxy)-2-undecynyl]phenyl methyl ether | C32H52O4Si | 详情 | 详情 | |
(XI) | 46584 | (4R,9aS)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-methoxy-3-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-1,4,9,9a-tetrahydro-2H-cyclopenta[b]naphthalen-2-one | C33H52O5Si | 详情 | 详情 | |
(XII) | 46585 | (1R,2R,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C27H42O4 | 详情 | 详情 | |
(XIII) | 46585 | (1R,2R,3aS,9aS)-5-methoxy-1-[(3S)-3-(tetrahydro-2H-pyran-2-yloxy)octyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C27H42O4 | 详情 | 详情 | |
(XIV) | 46571 | (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol | C22H34O3 | 详情 | 详情 | |
(XV) | 46572 | (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalene-2,5-diol | C21H32O3 | 详情 | 详情 | |
(XVI) | 46573 | 2-([(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl]oxy)acetonitrile | C23H33NO3 | 详情 | 详情 |