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【结 构 式】 
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【药物名称】B-1794, NSC-707390, ER-076349 【化学名称】(1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,35R,36S)-20-[2(S),3-Dihydroxypropyl]-21-methoxy-14-methyl-8,15-dimethylene-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.1(3,32).1(3,33).1(6,9).1(12,16).0(18,22).0(29,36).0(31,35)]hentetracontan-24-one 【CA登记号】253128-15-3, 253128-16-4 (diastereomer) 【 分 子 式 】C40H58O12 【 分 子 量 】730.90106 |
【开发单位】Eisai (Originator) 【药理作用】Oncolytic Drugs, Antimitotic Drugs |
合成路线1
Treatment of L-arabinose (I) with tert-butyldiphenylsilyl chloride and imidazole provided the mono-silylated furanose (II). The free hydroxyl groups of (II) were subsequently acylated with Ac2O, yielding the triacetate (III). Introduction of an allyl group in (III) by using the silyl reagent (IV) and boron trifluoride produced the allyl derivative (V) as a diastereomeric mixture. After basic hydrolysis of the acetate esters of (V), the required diastereoisomer (VI) was isolated by means of flash chromatography. Regioselective silylation of diol (VI) with tert-butyldiphenylsilyl chloride furnished (VII). Following methylation of the remaining free hydroxyl, the resultant methyl ether (VIII) was desilylated with methanolic HCl, giving diol (IX). Protection of the primary alcohol of (IX) was accomplished by acylation with pivaloyl chloride in pyridine, yielding (X). The secondary alcohol group of (X) was then converted to the benzyl ether (XI). Subsequent Sharpless asymmetric dihydroxylation of the allyl moiety of (XI) produced glycol (XII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Va) | 52367 | 4-(acetyloxy)-2-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)-5-(2-propenyl)tetrahydro-3-furanyl acetate | C28H36O6Si | 详情 | 详情 | |
| (Vb) | 52368 | 4-(acetyloxy)-2-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)-5-(2-propenyl)tetrahydro-3-furanyl acetate | C28H36O6Si | 详情 | 详情 | |
| (I) | 52364 | 2,3,4,5-tetrahydroxypentanal | C5H10O5 | 详情 | 详情 | |
| (II) | 52365 | 5-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)tetrahydro-2,3,4-furantriol | C21H28O5Si | 详情 | 详情 | |
| (III) | 52366 | 2,4-bis(acetyloxy)-5-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)tetrahydro-3-furanyl acetate | C27H34O8Si | 详情 | 详情 | |
| (IV) | 15775 | Allyltrimethylsilane; allyl(trimethyl)silane | 762-72-1 | C6H14Si | 详情 | 详情 |
| (VI) | 52369 | 2-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)-5-(2-propenyl)tetrahydro-3,4-furandiol | C24H32O4Si | 详情 | 详情 | |
| (VII) | 52370 | 4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)-2-(2-propenyl)tetrahydro-3-furanol | C30H46O4Si2 | 详情 | 详情 | |
| (VIII) | 52371 | (1,1-dimethylethyl)({[3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-4-(methyloxy)-5-(2-propenyl)tetrahydro-2-furanyl]methyl}oxy)diphenylsilane; (1,1-dimethylethyl)(dimethyl)silyl 2-({[(1,1-dimethylethyl)(diphenyl)silyl]oxy}methyl)-4-(methyloxy)-5-(2-propenyl)tetrahydro-3-furanyl ether | C31H48O4Si2 | 详情 | 详情 | |
| (IX) | 52372 | 2-(hydroxymethyl)-4-(methyloxy)-5-(2-propenyl)tetrahydro-3-furanol | C9H16O4 | 详情 | 详情 | |
| (X) | 52373 | [3-hydroxy-4-(methyloxy)-5-(2-propenyl)tetrahydro-2-furanyl]methyl 2,2-dimethylpropanoate | C14H24O5 | 详情 | 详情 | |
| (XI) | 52374 | [4-(methyloxy)-3-[(phenylmethyl)oxy]-5-(2-propenyl)tetrahydro-2-furanyl]methyl 2,2-dimethylpropanoate | C21H30O5 | 详情 | 详情 | |
| (XII) | 52375 | {5-(2,3-dihydroxypropyl)-4-(methyloxy)-3-[(phenylmethyl)oxy]tetrahydro-2-furanyl}methyl 2,2-dimethylpropanoate | C21H32O7 | 详情 | 详情 |
合成路线2
After silylation of diol (XII) to give (XIII), the O-benzyl group of (XIII) was removed by hydrogenolysis in the presence of Pearlman’s catalyst, yielding alcohol (XIV). Oxidation of alcohol (XIV) to the corresponding ketone (XV) was carried out by means of N-methylmorpholine-N-oxide in the presence of a catalytic amount of tetrapropylammonium perruthenate (TPAP). Ketone (XV) was then converted to the methylene derivative (XVI) by treatment with Tebbe's reagent, generated from bis(cyclopentadienyl)titanium and trimethylaluminum. Olefin (XVI) hydroboration by means of 9-borabicyclononane, followed by oxidative work-up with sodium perborate, provided the primary alcohol (XVII) as the undesired diastereoisomer. Configuration of alcohol (XVII) was inverted via Swern oxidation to the corresponding aldehyde, which was epimerized to (XVIII) under basic conditions. Further, aldehyde (XVIII) reduction with NaBH4 at 0 C generated alcohol (XIX). This was protected as the methoxybenzyl ether (XXI) by condensation with p-methoxybenzyl trichloroacetimidate (XX). The pivaloyl ester of (XXI) was then removed by reductive cleavage with LiAlH4, affording alcohol (XXII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 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) | 52375 | {5-(2,3-dihydroxypropyl)-4-(methyloxy)-3-[(phenylmethyl)oxy]tetrahydro-2-furanyl}methyl 2,2-dimethylpropanoate | C21H32O7 | 详情 | 详情 | |
| (XIII) | 52376 | {5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[(phenylmethyl)oxy]tetrahydro-2-furanyl}methyl 2,2-dimethylpropanoate | C33H60O7Si2 | 详情 | 详情 | |
| (XIV) | 52377 | [5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-3-hydroxy-4-(methyloxy)tetrahydro-2-furanyl]methyl 2,2-dimethylpropanoate | C26H54O7Si2 | 详情 | 详情 | |
| (XV) | 52378 | [5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-oxotetrahydro-2-furanyl]methyl 2,2-dimethylpropanoate | C26H52O7Si2 | 详情 | 详情 | |
| (XVI) | 52379 | [(2R,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxy-3-methylenetetrahydro-2-furanyl]methyl pivalate | C27H54O6Si2 | 详情 | 详情 | |
| (XVII) | 52380 | [(2R,3S,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-3-(hydroxymethyl)-4-methoxytetrahydro-2-furanyl]methyl pivalate | C27H56O7Si2 | 详情 | 详情 | |
| (XVIII) | 52381 | [(2R,3R,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-3-formyl-4-methoxytetrahydro-2-furanyl]methyl pivalate | C27H54O7Si2 | 详情 | 详情 | |
| (XIX) | 52382 | [5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-3-(hydroxymethyl)-4-(methyloxy)tetrahydro-2-furanyl]methyl 2,2-dimethylpropanoate | C27H56O7Si2 | 详情 | 详情 | |
| (XX) | 52385 | [4-(methyloxy)phenyl]methyl 2,2,2-trichloroethanimidoate | C10H10Cl3NO2 | 详情 | 详情 | |
| (XXI) | 52383 | {5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methyl 2,2-dimethylpropanoate | C35H64O8Si2 | 详情 | 详情 | |
| (XXII) | 52384 | {5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methanol | C30H56O7Si2 | 详情 | 详情 |
合成路线3
Homologation of alcohol (XXII) was effected by Swern oxidation to aldehyde (XXIII), which was then converted to the vinyl derivative (XXIV) by Wittig reaction with methylene triphenylphosphorane. Hydroboration of olefin (XXIV), followed by oxidative work-up, furnished alcohol (XXV). This was subjected to a further Swern oxidation to aldehyde (XXVI). Coupling of aldehyde (XXVI) with the known vinyl iodide (XXVII) produced a mixture of pyran derivative (XXVIII) and some uncyclized intermediate. Cyclization to (XXVIII) was completed by subsequent treatment of the reaction mixture with potassium hexamethyldisilazide. The p-methoxybenzyl protecting group of (XXVIII) was removed by oxidative treatment with DDQ. The desired diastereomer (XXIX) was then isolated by column chromatography.
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXII) | 52384 | {5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methanol | C30H56O7Si2 | 详情 | 详情 | |
| (XXIII) | 52386 | 5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furancarbaldehyde | C30H54O7Si2 | 详情 | 详情 | |
| (XXIV) | 52387 | 5-({5-ethenyl-3-(methyloxy)-4-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}methyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane; 2-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-5-ethenyl-4-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-3-furanyl methyl ether | C31H56O6Si2 | 详情 | 详情 | |
| (XXV) | 52388 | 2-{5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}-1-ethanol | C31H58O7Si2 | 详情 | 详情 | |
| (XXVI) | 52389 | 2-{5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-4-(methyloxy)-3-[({[4-(methyloxy)phenyl]methyl}oxy)methyl]tetrahydro-2-furanyl}acetaldehyde | C31H56O7Si2 | 详情 | 详情 | |
| (XXVII) | 52390 | 3-(5-{6-iodo-5-methyl-3-[(methylsulfonyl)oxy]-6-heptenyl}-4-methylidenetetrahydro-2-furanyl)propyl 2,2-dimethylpropanoate | C22H37IO6S | 详情 | 详情 | |
| (XXVIII) | 52391 | 3-[(2S,5S)-5-(2-{(2S,4R)-6-[((2S,3R,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxy-3-{[(4-methoxybenzyl)oxy]methyl}tetrahydro-2-furanyl)methyl]-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl}ethyl)-4-methylenetetrahydro-2-furanyl]propyl 2,2-dimethylpropanoate | C52H90O10Si2 | 详情 | 详情 | |
| (XXIX) | 52392 | 3-{5-[2-(6-{[5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-3-(hydroxymethyl)-4-(methyloxy)tetrahydro-2-furanyl]methyl}-4-methyl-5-methylidenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylidenetetrahydro-2-furanyl}propyl 2,2-dimethylpropanoate | C44H82O9Si2 | 详情 | 详情 |
合成路线4
Alcohol (XXIX) was converted to the corresponding tosylate (XXX) employing p-toluenesulfonyl chloride and pyridine. Replacement of the pivaloyl protecting group of (XXX) for a mono-methoxytrityl group, yielding (XXXII), was effected by reductive cleavage of the pivaloyl ester of (XXX) and then treatment of alcohol (XXXI) with methoxytrityl chloride. Displacement of the tosylate group of (XXXII) by NaI in refluxing acetone provided the alkyl iodide (XXXIII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIX) | 52392 | 3-{5-[2-(6-{[5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-3-(hydroxymethyl)-4-(methyloxy)tetrahydro-2-furanyl]methyl}-4-methyl-5-methylidenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylidenetetrahydro-2-furanyl}propyl 2,2-dimethylpropanoate | C44H82O9Si2 | 详情 | 详情 | |
| (XXX) | 52393 | 3-{(2S,5S)-5-[2-((2S,4R,6R)-6-{[(2S,3R,4R,5R)-5-((2S)-2,3-bis{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-methoxy-3-({[(4-methylphenyl)sulfonyl]oxy}methyl)tetrahydro-2-furanyl]methyl}-4-methyl-5-methylenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylenetetrahydro-2-furanyl}propyl 2,2-dimethylpropanoate | C51H88O11SSi2 | 详情 | 详情 | |
| (XXXI) | 52394 | [5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-2-[(6-{2-[5-(3-hydroxypropyl)-3-methylidenetetrahydro-2-furanyl]ethyl}-4-methyl-3-methylidenetetrahydro-2H-pyran-2-yl)methyl]-4-(methyloxy)tetrahydro-3-furanyl]methyl 4-methylbenzenesulfonate | C46H80O10SSi2 | 详情 | 详情 | |
| (XXXII) | 52395 | C66H96O11SSi2 | 详情 | 详情 | ||
| (XXXIII) | 52396 | C59H89IO8Si2 | 详情 | 详情 |
合成路线5
The aldehyde building block (XXXV) was obtained by DIBAL reduction of the previously described methyl ester (XXXIV). Lithiation of alkyl iodide (XXXIII) by means of tert-BuLi and then addition to aldehyde (XXXV) furnished the carbinol adduct (XXXVI). The methoxytrityl protecting group of (XXXVI) was then removed by acidic treatment, yielding (XXXVII). Oxidation of both free hydroxyl groups of (XXXVII) with Dess-Martin periodinane reagent gave rise to the keto aldehyde (XXXVIII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 52396 | C59H89IO8Si2 | 详情 | 详情 | ||
| (XXXIV) | 48420 | methyl 2-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-((1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-iodo-2-propenyl)octahydropyrano[3,2-b]pyran-2-yl]acetate | C32H63IO7Si3 | 详情 | 详情 | |
| (XXXV) | 52397 | C31H61IO6Si3 | 详情 | 详情 | ||
| (XXXVI) | 52398 | C90H151IO14Si5 | 详情 | 详情 | ||
| (XXXVII) | 52399 | C70H135IO13Si5 | 详情 | 详情 | ||
| (XXXVIII) | 52400 | C70H131IO13Si5 | 详情 | 详情 |
合成路线6
An alternative, more convenient preparation of intermediate (XXXVIII) from (XXIX) was also reported. Activation of alcohol (XXIX) as the triflate (XXXIX) by means of trifluoromethanesulfonic anhydride, followed by condensation with thiophenol, gave the phenyl thioether (XL). This was oxidized to sulfone (XLI) using N-methylmorpholine-N-oxide in the presence of TPAP. The pivaloyl protecting group of (XLI) was reductively cleaved with DIBAL, giving (XLII). The lithium anion generated from sulfone (XLII) in the presence of n-BuLi was then condensed with aldehyde (XXXV) to furnish the carbinol adduct (XLIII).
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIX) | 52392 | 3-{5-[2-(6-{[5-(2,3-bis{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)-3-(hydroxymethyl)-4-(methyloxy)tetrahydro-2-furanyl]methyl}-4-methyl-5-methylidenetetrahydro-2H-pyran-2-yl)ethyl]-4-methylidenetetrahydro-2-furanyl}propyl 2,2-dimethylpropanoate | C44H82O9Si2 | 详情 | 详情 | |
| (XXXV) | 52397 | C31H61IO6Si3 | 详情 | 详情 | ||
| (XXXIX) | 52401 | C45H81F3O11SSi2 | 详情 | 详情 | ||
| (XL) | 52402 | C50H86O8SSi2 | 详情 | 详情 | ||
| (XLI) | 52403 | C50H86O10SSi2 | 详情 | 详情 | ||
| (XLII) | 52404 | C45H78O9SSi2 | 详情 | 详情 | ||
| (XLIII) | 52405 | C76H139IO15SSi5 | 详情 | 详情 |
合成路线7
Dess-Martin oxidation of both alcohol functions of (XLIII) yielded the keto sulfone (XLIV). Reductive cleavage of the phenylsulfonyl group (XLIV) to afford (XXXVIII) was carried out by means of an in situ-generated SmI2 solution in THF.
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
合成路线8
Cyclization between the aldehyde and vinyl iodide moieties of (XXXVIII) was achieved by NiCl2/CrCl2-promoted intramolecular condensation. The resulting macrocyclic alcohol (XLV) was then oxidized to ketone (XLVI) with Dess-Martin periodinane reagent. Deprotection of (XLVI) with tetrabutylammonium fluoride furnished the fully desilylated compound (XLVII). The final cyclization between hydroxyl groups and the unsaturated ketone group of (XLVII) under acidic conditions gave rise to the title compound.
| 【1】 Littlefield, B.A.; Zheng, W.; Seletsky, B.M.; Yu, M.J.; Palme, M.H.; Towle, M.J. (Eisai Co., Ltd.); Macrocyclic analogs and methods of their use and preparation. US 6214865; WO 9965894 . |
合成路线9
The previously referenced vinyl iodide intermediate (XXXIV) was obtained as follows: The reaction of L-mannonic acid gamma-lactone (XLVIII) with cyclohexanone (XLIX) by means of H2SO4 in toluene gave the bis-cyclohexylidene ketal (L), which was reduced with DIBAL in dichloromethane to yield the lactol (LI). The condensation of (LI) with the phosphonium chloride (LII) by means of t-Bu-OK in refluxing THF afforded the vinyl ether (LIII), which was hydroxylated with OsO4 and dihydroquinidine-4-chlorobenzoate as chiral ligand and acylated with acetic anhydride and pyridine to provide the diacetate (LIV). The condensation of (LIV) with the functionalized allyl silane (LV) by means of BF3/Et2O in acetonitrile gave the adduct (LVI), which was submitted to cyclization by means of Triton B(OMe) in THF/methyl acetate to yield the perhydropyrano[3,2-b]pyran derivative (LVII). The selective hydrolysis of the exocyclic cyclohexylidene ketal of (LVII) with hot AcOH/water afforded the diol (LVIII), which by oxidative cleavage with NaIO4 in THF afforded the aldehyde (LIX). The coupling of (LIX) with the silylated vinyl iodide (LX), catalyzed by NiCl2 and CrCl2 in DMSO, gave the silylated allyl alcohol (LXI), which was submitted to cleavage of the cyclohexylidene ketal by means of AcOH/TFA to yield the trihydroxy compound (LXII). The protection of the three OH groups of (LXII) with Tbdms-OTf and lutidine in dichloromethane afforded the tris-Tbdms protected vinyl silane (LXIII), which was finally iodinated with N-iodosuccinimide (NIS) in acetonitrile/chloroacetonitrile to provide the target vinyl iodide intermediate (XXXIV).
| 【1】 Kishi, Y.; Stamos, D.P.; Synthetic studies on halichondrins: A practical synthesis of the C.1-C.13 segment. Tetrahedron Lett 1996, 37, 48, 8643. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIV) | 48420 | methyl 2-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-((1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-iodo-2-propenyl)octahydropyrano[3,2-b]pyran-2-yl]acetate | C32H63IO7Si3 | 详情 | 详情 | |
| (XLVIII) | 25665 | (3R,4S,5S)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxydihydro-2(3H)-furanone | C6H10O6 | 详情 | 详情 | |
| (XLIX) | 11059 | Cyclohexanone | 108-94-1 | C6H10O | 详情 | 详情 |
| (L) | 52411 | C18H26O6 | 详情 | 详情 | ||
| (LI) | 52412 | C18H28O6 | 详情 | 详情 | ||
| (LII) | 39163 | (methoxymethyl)(triphenyl)phosphonium chloride | 4009-98-7 | C20H20ClOP | 详情 | 详情 |
| (LIII) | 52413 | C20H32O6 | 详情 | 详情 | ||
| (LIV) | 52414 | C23H34O9 | 详情 | 详情 | ||
| (LV) | 52423 | methyl 3-(trimethylsilyl)-4-pentenoate | C9H18O2Si | 详情 | 详情 | |
| (LVI) | 52415 | C27H40O9 | 详情 | 详情 | ||
| (LVII) | 52416 | C25H38O8 | 详情 | 详情 | ||
| (LVIII) | 52417 | C19H30O8 | 详情 | 详情 | ||
| (LIX) | 52418 | C18H26O7 | 详情 | 详情 | ||
| (LX) | 52419 | (2-iodoethenyl)(trimethyl)silane | C5H11ISi | 详情 | 详情 | |
| (LXI) | 52420 | C23H38O7Si | 详情 | 详情 | ||
| (LXII) | 52421 | methyl 2-{(2R,4aS,6S,7S,8R,8aR)-7,8-dihydroxy-6-[(E)-1-hydroxy-3-(trimethylsilyl)-2-propenyl]octahydropyrano[3,2-b]pyran-2-yl}acetate | C17H30O7Si | 详情 | 详情 | |
| (LXIII) | 52422 | methyl 2-{(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tert-butyl(dimethyl)silyl]oxy}-6-[(1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-(trimethylsilyl)-2-propenyl]octahydropyrano[3,2-b]pyran-2-yl}acetate | C35H72O7Si4 | 详情 | 详情 |