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【结 构 式】 
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【分子编号】25805 【品名】1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate 【CA登记号】1005-56-7 |
【 分 子 式 】C7H5ClOS 【 分 子 量 】172.6348 【元素组成】C 48.7% H 2.92% Cl 20.54% O 9.27% S 18.57% |
合成路线1
该中间体在本合成路线中的序号：(V)A new synthesis of didanosine has been described: Treatment of 2'-deoxyadenosine (I) with adenosine deaminase (ADA) in water gives 2'-deoxyinosine (II), which is treated with vinyl acetate (III) and Candida antarctica lipase (CAL) in hot pyridine yielding 5'-O-acetyl-2'-deoxyinosine (IV). The reaction of (IV) with phenyl chlorothionoformate (V) and DMAP in acetonitrile affords the corresponding thiocarbonate (VI), which is treated with tributylstannane and AIBN in hot toluene to provide 5'-O-acetyl-2',3'-dideoxyinosine (VII). Finally, this compound is deacetylated with NH3 in methanol.
| 【1】 Santaniello, E.; Ciuffreda, P.; Casati, S.; Lipase-catalyzed protection of the hydroxy groups of the nucleosides inosine and 2'-deoxyinosine: A new chemoenzymatic synthesis of the antiviral drug 2',3'-dideoxyinosine. Bioorg Med Chem Lett 1999, 9, 11, 1577. |
| 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) | 18061 | (2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydro-3-furanol | 958-09-8 | C10H13N5O3 | 详情 | 详情 |
| (II) | 12801 | 9-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-6-ol | 890-38-0 | C10H12N4O4 | 详情 | 详情 |
| (III) | 24543 | vinyl acetate | 108-05-4 | C4H6O2 | 详情 | 详情 |
| (IV) | 37609 | [(2R,3S,5R)-3-hydroxy-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C12H14N4O5 | 详情 | 详情 | |
| (V) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (VI) | 37610 | [(2R,3S,5R)-5-(6-hydroxy-9H-purin-9-yl)-3-[(phenoxycarbothioyl)oxy]tetrahydro-2-furanyl]methyl acetate | C19H18N4O6S | 详情 | 详情 | |
| (VII) | 37611 | [(2S,5R)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C12H14N4O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：A new synthesis of lodenosine has been described: The selective benzoylation of the 6-chloropurine riboside (I) with benzoyl chloride and triethylamine through the formation of a complex with dibutyl tin oxide, gives the 3'-O-benzoyl derivative (II), which is purified by crystallization (minor impurities, about 3%, of the 2'-O derivative are present). The protection of the primary OH group of (II) by reaction with trityl chloride, DMAP and Et3N in DMF yields the 5'-O-trityl derivative (III), which is treated with DAST and pyridine to afford the fluorinated arabinofuranoside (IV). The reaction of (IV) with ammonia in methanol displaces the 6-Cl atom and hydrolyzes the 3'-O-benzoyl group giving the fluorinated arabinofuranosyladenine (V). The reaction of (V) with phenyl chlorothionoformate and DMAP in acetonitrile yields the thiocarbonate (VI), which is treated with tris(trimethylsilyl)silane and AIBN in hot toluene to afford the 3'-deoxy compound (VII). Finally, this compound is deprotected by reaction with HCl in methanol/water.
| 【1】 Izawa, K.; Satoh, Y.; Takamatsu, S.; Kozai, S.; Maruyama, T.; Synthesis of 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine bearing selectively removable protecting group. Chem Pharm Bull 1999, 47, 7, 966. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 | |
| (I) | 18716 | 6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 2004-06-0 | C10H11ClN4O4 | 详情 | 详情 |
| (II) | 29871 | (2R,3S,4R,5R)-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-2-(hydroxymethyl)tetrahydro-3-furanyl benzoate | C17H15ClN4O5 | 详情 | 详情 | |
| (III) | 29872 | (2R,3S,4R,5R)-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-2-[(trityloxy)methyl]tetrahydro-3-furanyl benzoate | C36H29ClN4O5 | 详情 | 详情 | |
| (IV) | 29873 | (2R,3R,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluoro-2-[(trityloxy)methyl]tetrahydro-3-furanyl benzoate | C36H28ClFN4O4 | 详情 | 详情 | |
| (V) | 29874 | (2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-2-[(trityloxy)methyl]tetrahydro-3-furanol | C29H26FN5O3 | 详情 | 详情 | |
| (VI) | 29875 | O-[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-2-[(trityloxy)methyl]tetrahydro-3-furanyl] O-phenyl carbonothioate | C36H30FN5O4S | 详情 | 详情 | |
| (VII) | 29876 | 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-amine | C29H26FN5O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VII)An improved synthesis of lodenosine has been reported: The reaction of the chloropurine derivative (I) with trityl chloride and diisopropylamine in DMF gives the 5'-O-trityl-purine (II), which is treated with benzoyl chloride and pyridine in toluene to afford the 3'-O-benzoyl-5'-O-trityl-purine (III) -- some of the 2'-O-benzyl regioisomer is also isolated and is recycled after acyl migration by reaction with TEA. The reaction of purine (III) with trifluoromethanesulfonyl chloride and DMAP in toluene yields the 3'-O-benzoyl-2'-O-sulfonyl-5'-O-trityl-purine (IV), which is treated with HF and TEA to provide the 2'-beta-fluoro-purine (V). The reaction of compound (V) with ammonia in methanol gives the adenosine derivative (VI), which is treated with O-phenyl chlorothioformate and DMAP in pyridine to yield the thiocarbonate (VIII). The deoxygenation of (VIII) is performed with diphenylsilane and AIBN affording 5'-O-trityl-lodenosine (IX), which is finally deprotected with 80% HOAc.
| 【1】 Katayama, S.; Hirose, N.; Izawa, K.; Takamatsu, S.; Maruyama, T.; Improved synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) using triethylamine trihydrofluoride. Tetrahedron Lett 2001, 42, 12, 2321. |
| 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) | 18716 | 6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 2004-06-0 | C10H11ClN4O4 | 详情 | 详情 |
| (II) | 48718 | (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-[(trityloxy)methyl]tetrahydro-3,4-furandiol | C29H25ClN4O4 | 详情 | 详情 | |
| (III) | 29872 | (2R,3S,4R,5R)-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-2-[(trityloxy)methyl]tetrahydro-3-furanyl benzoate | C36H29ClN4O5 | 详情 | 详情 | |
| (IV) | 48719 | (2R,3R,4R,5R)-5-(6-chloro-9H-purin-9-yl)-4-[[(trifluoromethyl)sulfonyl]oxy]-2-[(trityloxy)methyl]tetrahydro-3-furanyl benzoate | C37H28ClF3N4O7S | 详情 | 详情 | |
| (V) | 29873 | (2R,3R,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluoro-2-[(trityloxy)methyl]tetrahydro-3-furanyl benzoate | C36H28ClFN4O4 | 详情 | 详情 | |
| (VI) | 29875 | O-[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-2-[(trityloxy)methyl]tetrahydro-3-furanyl] O-phenyl carbonothioate | C36H30FN5O4S | 详情 | 详情 | |
| (VII) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (VIII) | 29875 | O-[(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluoro-2-[(trityloxy)methyl]tetrahydro-3-furanyl] O-phenyl carbonothioate | C36H30FN5O4S | 详情 | 详情 | |
| (IX) | 29876 | 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-amine | C29H26FN5O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XX)Synthesis of the target epothilone: The condensation of the iodinated dioxolane (XI) with the phenylsulfone (XII) by means of BuLi and DMPU gives the adduct (XIII), which is deprotected with Amberlyst 15 to yield the diol (XIV). Regioselective silylation of (XIV) with Tbdms-Cl and imidazole affords the monosilylated diol (XV), which is fully protected with Sem-Cl and DIEA, providing compound (XVI). The reaction of (XVI) with tributyltin hydride gives the stannane (XVII), which is condensed with the chiral aldehyde (XVIII) by means of SnBr4 to yield the 4-decanol derivative (XIX). The elimination of The OH group of (XIX) is performed via its reaction with Cl-C(S)-OPh (XX) to afford the thiocarbonate (XXI), which is then treated with tributyltin hydride to provide the dehydroxylated compound (XXII). Selective deprotection of (XXII) with DDQ gives the primary alcohol (XXIII), which is esterified with pivaloyl chloride, yielding the pivaloyl ester (XXIV). The selective desilylation of the Tbdms group of (XXIV) with TBAF gives the primary alcohol (XXV), which is oxidized to the corresponding aldehyde (XXVI) by means of DMP. The Grignard reaction of aldehyde (XXVI) with methylmagnesium bromide yields the secondary alcohol (XXVII).
| 【1】 Martin, N.; Thomas, E.J.; Total syntheses of epothilones B and D: Applications of allylstannanes in organic synthesis. Tetrahedron Lett 2001, 42, 47, 8373. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 51436 | (4R)-4-(iodomethyl)-2,2-dimethyl-1,3-dioxolane | C6H11IO2 | 详情 | 详情 | |
| (XII) | 51457 | (8S,10Z,15S,16S,17R,20S)-16-[[tert-butyl(dimethyl)silyl]oxy]-20-(2-hydroxyethyl)-2,2,11,15,17,19,19,22,22,23,23-undecamethyl-8-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5,7,21-trioxa-2lambda(4)-thia-22-sila-10-tetracosen-18-one | C45H87NO6S2Si2 | 详情 | 详情 | |
| (XIII) | 51438 | 1-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-methyl-2-propenyl phenyl sulfone; (4S)-2,2-dimethyl-4-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-1,3-dioxolane | C16H22O4S | 详情 | 详情 | |
| (XIV) | 51439 | (2S)-5-methyl-4-(phenylsulfonyl)-5-hexene-1,2-diol | C13H18O4S | 详情 | 详情 | |
| (XV) | 51440 | (2S)-1-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-4-(phenylsulfonyl)-5-hexen-2-ol | C19H32O4SSi | 详情 | 详情 | |
| (XVI) | 51441 | 1-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]propyl)-2-methyl-2-propenyl phenyl sulfone; (8S)-2,2,11,11,12,12-hexamethyl-8-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C25H46O5S2Si | 详情 | 详情 | |
| (XVII) | 51442 | tert-butyl(dimethyl)silyl (2S,4E)-5-methyl-6-(tributylstannyl)-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-hexenyl ether; (8S)-2,2,11,11,12,12-hexamethyl-8-[(E)-3-methyl-4-(tributylstannyl)-2-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C31H68O3SSiSn | 详情 | 详情 | |
| (XVIII) | 51443 | (3S)-4-[(4-methoxybenzyl)oxy]-3-methylbutanal | C13H18O3 | 详情 | 详情 | |
| (XIX) | 51444 | (8S,10Z,15S)-8-([[tert-butyl(dimethyl)silyl]oxy]methyl)-18-(4-methoxyphenyl)-2,2,11,15-tetramethyl-5,7,17-trioxa-2lambda(4)-thia-10-octadecen-13-ol | C32H60O6SSi | 详情 | 详情 | |
| (XX) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (XXI) | 51445 | O-((Z,6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-1-[(2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropyl]-3-methyl-6-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-3-heptenyl) O-phenyl carbonothioate | C39H64O7S2Si | 详情 | 详情 | |
| (XXII) | 51446 | tert-butyl(dimethyl)silyl (2S,4Z,9S)-10-[(4-methoxybenzyl)oxy]-5,9-dimethyl-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-decenyl ether; (8S)-8-[(Z,7S)-8-[(4-methoxybenzyl)oxy]-3,7-dimethyl-2-octenyl]-2,2,11,11,12,12-hexamethyl-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C32H60O5SSi | 详情 | 详情 | |
| (XXIII) | 51447 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decen-1-ol | C24H52O4SSi | 详情 | 详情 | |
| (XXIV) | 51448 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C29H60O5SSi | 详情 | 详情 | |
| (XXV) | 51449 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H46O5S | 详情 | 详情 | |
| (XXVI) | 51450 | (2S,6Z,9S)-2,6-dimethyl-10-oxo-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H44O5S | 详情 | 详情 | |
| (XXVII) | 51451 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-undecenyl pivalate | C24H48O5S | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(IV)The condensation of decanal (I) with silyl enol ether (II) by means of a chiral catalyst and Sn(OTf)2 in dichloromethane gives the chiral thiocarboxylic ester (III), which is treated with chlorothioformate (IV) and pyridine in refluxing dichloroethane to yield the thiocarbonic ester (V). The reduction of (V) with Bu3SnH and AIBN in refluxing toluene affords the chiral thioester (VI), which is reduced with LiAlH4 in THF to provide the alcohol (VII). The oxidation of (VII) with oxalyl chloride in DMSO/dichloromethane gives the corresponding aldehyde (VIII), which is condensed with phosphorane (IX) to yield the unsaturated ester (X). The reduction of the ester group of (X) with DIBAL in dichloromethane affords the allyl alcohol (XI), which is submitted to a Sharpless epoxidation with tert-butyl hydroperoxide (TBHP) and Ti(O-iPr)4 in the presence of diethyl D-tartrate, providing the chiral epoxide (XII). Methylation of the epoxide ring of (XII) with MeLi and CuI in ethyl ether gives the diol (XIII), which is treated with the dimethyl acetal (XIV) and Ts-OH in dichloromethane to yield the 1,3-dioxane (XV). The reductive cleavage of (XV) with DIBAL in the same solvent affords the Pmb ether (XVI), whose primary alcohol is oxidized with oxalyl chloride in DMSO/dichloromethane to provide the aldehyde (XVII). The condensation of (XVII) with phosphorane (XVIII) in refluxing THF gives the unsaturated ester (XIX).
| 【1】 Wakabayashi, T.; Mori, K.; Kobayashi, S.; Total synthesis and structural elucidation of khafrefungin. J Am Chem Soc 2001, 123, 7, 1372. |
| 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) | 31059 | decanal | 112-31-2 | C10H20O | 详情 | 详情 |
| (II) | 47158 | (Z)-1-(propylsulfanyl)-1-propenyl trimethylsilyl ether; trimethyl[[(Z)-1-(propylsulfanyl)-1-propenyl]oxy]silane | C9H20OSSi | 详情 | 详情 | |
| (III) | 47159 | S-propyl (2S,3R)-3-hydroxy-2-methyldodecanethioate | C16H32O2S | 详情 | 详情 | |
| (IV) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (V) | 47160 | S-propyl (2S,3R)-2-methyl-3-[(phenoxycarbothioyl)oxy]dodecanethioate | C23H36O3S2 | 详情 | 详情 | |
| (VI) | 47161 | S-propyl (2S)-2-methyldodecanethioate | C16H32OS | 详情 | 详情 | |
| (VII) | 47162 | (2S)-2-methyl-1-dodecanol | C13H28O | 详情 | 详情 | |
| (VIII) | 47163 | (2S)-2-methyldodecanal | C13H26O | 详情 | 详情 | |
| (IX) | 47164 | propyl 2-(triphenylphosphoranylidene)acetate | C23H23O2P | 详情 | 详情 | |
| (X) | 47165 | propyl (E,4S)-4-methyl-2-tetradecenoate | C18H34O2 | 详情 | 详情 | |
| (XI) | 47166 | (E,4S)-4-methyl-2-tetradecen-1-ol | C15H30O | 详情 | 详情 | |
| (XII) | 47167 | [(2S,3R)-3-[(1S)-1-methylundecyl]oxiranyl]methanol | C15H30O2 | 详情 | 详情 | |
| (XIII) | 47168 | (2S,3R,4S)-2,4-dimethyl-1,3-tetradecanediol | C16H34O2 | 详情 | 详情 | |
| (XIV) | 26485 | 1-(dimethoxymethyl)-4-methoxybenzene | 2186-92-7 | C10H14O3 | 详情 | 详情 |
| (XV) | 47169 | (4R,5S)-2-(4-methoxyphenyl)-5-methyl-4-[(1S)-1-methylundecyl]-1,3-dioxane; methyl 4-[(4R,5S)-5-methyl-4-[(1S)-1-methylundecyl]-1,3-dioxan-2-yl]phenyl ether | C24H40O3 | 详情 | 详情 | |
| (XVI) | 47170 | (2S,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyl-1-tetradecanol | C24H42O3 | 详情 | 详情 | |
| (XVII) | 47171 | (2R,3R,4S)-3-[(4-methoxybenzyl)oxy]-2,4-dimethyltetradecanal | C24H40O3 | 详情 | 详情 | |
| (XVIII) | 47172 | propyl 2-(triphenylphosphoranylidene)propanoate | C24H25O2P | 详情 | 详情 | |
| (XIX) | 47173 | propyl (E,4S,5R,6S)-5-[(4-methoxybenzyl)oxy]-2,4,6-trimethyl-2-hexadecenoate | C30H50O4 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XX)Synthesis of the target epothilone: The condensation of the iodinated dioxolane (XI) with the phenylsulfone (XII) by means of BuLi and DMPU gives the adduct (XIII), which is deprotected with Amberlyst 15 to yield the diol (XIV). Regioselective silylation of (XIV) with Tbdms-Cl and imidazole affords the monosilylated diol (XV), which is fully protected with Sem-Cl and DIEA, providing compound (XVI). The reaction of (XVI) with tributyltin hydride gives the stannane (XVII), which is condensed with the chiral aldehyde (XVIII) by means of SnBr4 to yield the 4-decanol derivative (XIX). The elimination of The OH group of (XIX) is performed via its reaction with Cl-C(S)-OPh (XX) to afford the thiocarbonate (XXI), which is then treated with tributyltin hydride to provide the dehydroxylated compound (XXII). Selective deprotection of (XXII) with DDQ gives the primary alcohol (XXIII), which is esterified with pivaloyl chloride, yielding the pivaloyl ester (XXIV). The selective desilylation of the Tbdms group of (XXIV) with TBAF gives the primary alcohol (XXV), which is oxidized to the corresponding aldehyde (XXVI) by means of DMP. The Grignard reaction of aldehyde (XXVI) with methylmagnesium bromide yields the secondary alcohol (XXVII).
| 【1】 Martin, N.; Thomas, E.J.; Total syntheses of epothilones B and D: Applications of allylstannanes in organic synthesis. Tetrahedron Lett 2001, 42, 47, 8373. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 51436 | (4R)-4-(iodomethyl)-2,2-dimethyl-1,3-dioxolane | C6H11IO2 | 详情 | 详情 | |
| (XII) | 51457 | (8S,10Z,15S,16S,17R,20S)-16-[[tert-butyl(dimethyl)silyl]oxy]-20-(2-hydroxyethyl)-2,2,11,15,17,19,19,22,22,23,23-undecamethyl-8-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5,7,21-trioxa-2lambda(4)-thia-22-sila-10-tetracosen-18-one | C45H87NO6S2Si2 | 详情 | 详情 | |
| (XIII) | 51438 | 1-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-methyl-2-propenyl phenyl sulfone; (4S)-2,2-dimethyl-4-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-1,3-dioxolane | C16H22O4S | 详情 | 详情 | |
| (XIV) | 51439 | (2S)-5-methyl-4-(phenylsulfonyl)-5-hexene-1,2-diol | C13H18O4S | 详情 | 详情 | |
| (XV) | 51440 | (2S)-1-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-4-(phenylsulfonyl)-5-hexen-2-ol | C19H32O4SSi | 详情 | 详情 | |
| (XVI) | 51441 | 1-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]propyl)-2-methyl-2-propenyl phenyl sulfone; (8S)-2,2,11,11,12,12-hexamethyl-8-[3-methyl-2-(phenylsulfonyl)-3-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C25H46O5S2Si | 详情 | 详情 | |
| (XVII) | 51442 | tert-butyl(dimethyl)silyl (2S,4E)-5-methyl-6-(tributylstannyl)-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-hexenyl ether; (8S)-2,2,11,11,12,12-hexamethyl-8-[(E)-3-methyl-4-(tributylstannyl)-2-butenyl]-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C31H68O3SSiSn | 详情 | 详情 | |
| (XVIII) | 51443 | (3S)-4-[(4-methoxybenzyl)oxy]-3-methylbutanal | C13H18O3 | 详情 | 详情 | |
| (XIX) | 51444 | (8S,10Z,15S)-8-([[tert-butyl(dimethyl)silyl]oxy]methyl)-18-(4-methoxyphenyl)-2,2,11,15-tetramethyl-5,7,17-trioxa-2lambda(4)-thia-10-octadecen-13-ol | C32H60O6SSi | 详情 | 详情 | |
| (XX) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (XXI) | 51445 | O-((Z,6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-1-[(2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropyl]-3-methyl-6-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-3-heptenyl) O-phenyl carbonothioate | C39H64O7S2Si | 详情 | 详情 | |
| (XXII) | 51446 | tert-butyl(dimethyl)silyl (2S,4Z,9S)-10-[(4-methoxybenzyl)oxy]-5,9-dimethyl-2-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-4-decenyl ether; (8S)-8-[(Z,7S)-8-[(4-methoxybenzyl)oxy]-3,7-dimethyl-2-octenyl]-2,2,11,11,12,12-hexamethyl-5,7,10-trioxa-2lambda(4)-thia-11-silatridecane | C32H60O5SSi | 详情 | 详情 | |
| (XXIII) | 51447 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decen-1-ol | C24H52O4SSi | 详情 | 详情 | |
| (XXIV) | 51448 | (2S,6Z,9S)-10-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C29H60O5SSi | 详情 | 详情 | |
| (XXV) | 51449 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H46O5S | 详情 | 详情 | |
| (XXVI) | 51450 | (2S,6Z,9S)-2,6-dimethyl-10-oxo-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-decenyl pivalate | C23H44O5S | 详情 | 详情 | |
| (XXVII) | 51451 | (2S,6Z,9S)-10-hydroxy-2,6-dimethyl-9-[[2-(trimethyl-lambda(4)-sulfanyl)ethoxy]methoxy]-6-undecenyl pivalate | C24H48O5S | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(VI)Dipolar cycloaddition of hydroxypyridinium betaine (I) with R-(+)-p-tolyl vinyl sulfoxide (II) furnished the chiral tropenone (III). Subsequent copper-catalyzed conjugate addition of phenyl-magnesium bromide on the beta-face of (III) provided the trans diaryltropanone (IV). Then, ketone reduction of (IV) with LiAlH4 gave alcohol (V), which was condensed with phenyl thionochloroformate (VI) to afford thiocarbonate (VII). This was reduced with tributyltin hydride and azobis(isobutyronitrile) to produce tropane (VIII). The sulfoxide group of (VIII) was further reduced to sulfide (IX) with PCl3 in DMF. Finally, Raney Nickel-promoted desulfurization in boiling EtOH yielded the title compound.
| 【1】 Kozikowski, A.P.; Araldi, G.L.; Prakash, K.R.; Zhang, M.; Johnson, K.M.; Synthesis and biological properties of new 2beta-alkyl- and 2beta-aryl-3-(substituted phenyl)tropane derivatives: Stereochemical effect of C-3 on affinity and selectivity for neuronal dopamine and serotonin transporters. J Med Chem 1998, 41, 25, 4973. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 | |
| (I) | 25800 | 1-methyl-4-(4-methylphenyl)-3-pyridiniumolate | C13H13NO | 详情 | 详情 | |
| (II) | 25801 | (4-methylphenyl)(oxo)vinyl-lambda(4)-sulfane; 4-methylphenyl vinyl sulfoxide | C9H10OS | 详情 | 详情 | |
| (III) | 25802 | (1S,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one | C22H23NO2S | 详情 | 详情 | |
| (IV) | 25803 | (1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]octan-2-one | C28H29NO2S | 详情 | 详情 | |
| (V) | 25804 | (1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]octan-2-ol | C28H31NO2S | 详情 | 详情 | |
| (VI) | 25805 | 1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate | 1005-56-7 | C7H5ClOS | 详情 | 详情 |
| (VII) | 25806 | O-[(1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]oct-2-yl] O-phenyl carbonothioate | C35H35NO3S2 | 详情 | 详情 | |
| (VIII) | 25807 | (1R,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-4-phenyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfoxide; (1S,2R,3R,5R,7R)-8-methyl-3-(4-methylphenyl)-7-[(4-methylphenyl)sulfinyl]-2-phenyl-8-azabicyclo[3.2.1]octane | C28H31NOS | 详情 | 详情 | |
| (IX) | 25808 | (1R,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-4-phenyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfide; (1S,2R,3R,5R,7R)-8-methyl-3-(4-methylphenyl)-7-[(4-methylphenyl)sulfanyl]-2-phenyl-8-azabicyclo[3.2.1]octane | C28H31NS | 详情 | 详情 |