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【结 构 式】 
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【分子编号】26254 【品名】4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide 【CA登记号】 |
【 分 子 式 】C12H10OS 【 分 子 量 】202.2768 【元素组成】C 71.25% H 4.98% O 7.91% S 15.85% |
合成路线1
该中间体在本合成路线中的序号：(IX)The intermediate sulfone alcohol (V) has been obtained by an alternative procedure. 4-Phenoxyphenol (VII) was converted to thiophenol (IX) through the sequence of condensation with N,N-dimethylthiocarbamyl chloride, followed by thermal rearrangement of the resulting O-aryl thiocarbamate (VIII) to the S-aryl thiocarbamate, and then hydrolysis with KOH. Alkylation with 3-chloropropanol (II) provided thioether (X), which was then oxidized to the sulfone (V) with Oxone(R).
| 【1】 Inturrisi, C.E.; Collins, J.J.; Dunkel, I.J.; Portenoy, R.K.; Palmer, L.N.; Lapin, J.; Gupta, S.K.; Weinstein, S.M.; Transdermal fentanyl in children with cancer pain: Feasibility, tolerability, and pharmacokinetic correlates. J Pediatr 1999, 134, 3, 319. |
| 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) | 19490 | 3-chloro-1-propanol | 627-30-5 | C3H7ClO | 详情 | 详情 |
| (V) | 27078 | 3-[(4-phenoxyphenyl)sulfonyl]-1-propanol | C15H16O4S | 详情 | 详情 | |
| (VII) | 27080 | 4-Phenoxyphenol | 831-82-3 | C12H10O2 | 详情 | 详情 |
| (VIII) | 27081 | O-(4-phenoxyphenyl) dimethylcarbamothioate | C15H15NO2S | 详情 | 详情 | |
| (IX) | 26254 | 4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide | C12H10OS | 详情 | 详情 | |
| (X) | 27082 | 3-[(4-phenoxyphenyl)sulfanyl]-1-propanol | C15H16O2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Michael addition of 4-(phenoxy)thiophenol (II) to cyclohexenone (I) afforded the ketosulfide (III). This was reduced with NaBH4 to give a diastereomeric mixture of alcohols (IV). Subsequent oxidation of sulfide group of (IV) with Oxone provided sulfone (V). Condensation with potassium thioacetate under Mitsunobu conditions gave the corresponding thioester as a mixture of isomers, from which the major trans isomer (VI) was isolated by chromatography. Finally, deprotection of (VI) with sodium methoxide in MeOH yielded the target thiol.
| 【1】 Mischke, B.V.; Freskos, J.N.; Stevens, A.M.; Mullins, P.B.; McDonald, J.J.; Stegeman, R.A.; Shieh, H.-S.; Synthesis and identification of conformationally constrained selective MMP inhibitors. Bioorg Med Chem Lett 1999, 9, 13, 1757. |
| 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) | 26253 | 2-cyclohexen-1-one；Cyclohex-2-enone；2-cyclohexenone | 930-68-7 | C6H8O | 详情 | 详情 |
| (II) | 26254 | 4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide | C12H10OS | 详情 | 详情 | |
| (III) | 26255 | 3-[(4-phenoxyphenyl)sulfanyl]cyclohexanone | C18H18O2S | 详情 | 详情 | |
| (IV) | 26256 | 3-[(4-phenoxyphenyl)sulfanyl]cyclohexanol | C18H20O2S | 详情 | 详情 | |
| (V) | 26257 | 3-[(4-phenoxyphenyl)sulfonyl]cyclohexanol | C18H20O4S | 详情 | 详情 | |
| (VI) | 26258 | S-[(1S,3S)-3-[(4-phenoxyphenyl)sulfonyl]cyclohexyl] ethanethioate | C20H22O4S2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)Treatment of 4-phenoxyphenol (I) with N,N-dimethylthiocarbamoyl chloride afforded the O-aryl thiocarbamate (II), which was thermally rearranged to the S-aryl thiocarbamate (III). Basic hydrolysis of (III) provided 4-phenoxythiophenol (IV). Subsequent alkylation of (IV) with allyl bromide (V) led to the allyl thioether (VI). Further oxidation of (VI) with m-chloroperbenzoic acid (MCPBA) gave rise to the epoxisulfone (VII). This was finally converted to the target thiirane derivative upon treatment with ammonium thiocyanate.
| 【1】 Kotra, L.P.; Brown, S.; Bernardo, M.M.; Tanaka, Y.; Li, Z.-H.; Fridman, R.; Mobashery, S.; Potent and selective mechanism-based inhibition of gelatinases. J Am Chem Soc 2000, 122, 28, 6799. |
| 【2】 Mobashery, S.; Fridman, R. (Wayne State University); Inhibitors of matrix metalloproteinases. WO 0192244 . |
| 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) | 27080 | 4-Phenoxyphenol | 831-82-3 | C12H10O2 | 详情 | 详情 |
| (II) | 27081 | O-(4-phenoxyphenyl) dimethylcarbamothioate | C15H15NO2S | 详情 | 详情 | |
| (III) | 46031 | S-(4-phenoxyphenyl) dimethylcarbamothioate | C15H15NO2S | 详情 | 详情 | |
| (IV) | 26254 | 4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide | C12H10OS | 详情 | 详情 | |
| (V) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (VI) | 46032 | 1-(allylsulfanyl)-4-phenoxybenzene; 4-(allylsulfanyl)phenyl phenyl ether | C15H14OS | 详情 | 详情 | |
| (VII) | 46033 | 2-[[(4-phenoxyphenyl)sulfonyl]methyl]oxirane; 2-oxiranylmethyl 4-phenoxyphenyl sulfone | C15H14O4S | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(III)The reaction of N-(benzyloxycarbonyl)-L-serine methyl ester (I) with Ts-Cl gives the corresponding tosylate (II), which is condensed with 4-phenoxythiophenol (III) to yield the thioether (IV). The oxidation of (IV) with Oxone affords the sulfone (V), which is N-deprotected with H2 over Pd/C to provide compound (VI) with a free amino group. The methylation of (VI) with methyl iodide gives the N-methyl derivative (VII), which is finally treated with hydroxylamine to afford the target hydroxamic acid.
| 【1】 Bedell, L.; Becker, D.P.; Barta, T.E.; et al.; alpha-Amino-beta-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1. Bioorg Med Chem Lett 2001, 11, 20, 2719. |
| 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) | 51660 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxypropanoate | C12H15NO5 | 详情 | 详情 | |
| (II) | 51655 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[[(4-methylphenyl)sulfonyl]oxy]propanoate | C19H21NO7S | 详情 | 详情 | |
| (III) | 26254 | 4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide | C12H10OS | 详情 | 详情 | |
| (IV) | 51656 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-[(4-phenoxyphenyl)sulfanyl]propanoate | C24H23NO5S | 详情 | 详情 | |
| (V) | 51657 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-[(4-phenoxyphenyl)sulfonyl]propanoate | C24H23NO7S | 详情 | 详情 | |
| (VI) | 51658 | methyl (2R)-2-amino-3-[(4-phenoxyphenyl)sulfonyl]propanoate | C16H17NO5S | 详情 | 详情 | |
| (VII) | 51659 | methyl (2R)-2-(methylamino)-3-[(4-phenoxyphenyl)sulfonyl]propanoate | C17H19NO5S | 详情 | 详情 |