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【结 构 式】 
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【分子编号】22649 【品名】(1S,3R,7S,8S,8aR)-8-[2-((2R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-oxotetrahydro-2H-pyran-2-yl)ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate 【CA登记号】 |
【 分 子 式 】C31H52O5Si 【 分 子 量 】532.83638 【元素组成】C 69.88% H 9.84% O 15.01% Si 5.27% |
合成路线1
该中间体在本合成路线中的序号：(V)The deacylation of lovastatin (I) with aqueous LiOH gives the free diol (II), which is partially protected with tert-butyldimethylsilyl chloride as usual, yielding the monosilylated derivative (III). The acylation of (III) with 2,2-dimethylbutyryl chloride (IV) by means of 4-pyrrolidino pyridine (py-py) in pyridine affords the silylated ester (V), which is finally deprotected with tetrabutylammonium fluoride and acetic acid in THF.
| 【1】 Hoffman, W.F.; Alberts, A. W.; Anderson, P.S.; Smith, R.L.; Chen, J.S.; Willard, A.K.; 3-Hydroxy-3-methylglutaryl-coenzyme A reductase in. J Med Chem 1986, 29, 5, 849. |
| 【2】 Hoffman, W.F.; Smith, R.L.; Willard, A.K. (Merck & Co., Inc.); Antihypercholesterolemic cpds.. US 4444784 . |
| 【3】 Askin, D.; et al.; Synthesis of synvinolin: Extremely high conversion alkylation of an ester enolate. J Org Chem 1991, 56, 16, 4929. |
| 【4】 Zlicar, M. (LEK Pharmaceutical and Chemical Co.); Process for the preparation of simvastatin and analogs thereof. WO 0032585 . |
| 【5】 Prous, J.; Castaner, J.; Simvastatin. Drugs Fut 1988, 13, 6, 531. |
| 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) | 22645 | (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate; Lovastatin | 75330-75-5 | C24H36O5 | 详情 | 详情 |
| (II) | 22646 | (4R,6R)-6-[2-[(1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydro-1-naphthalenyl]ethyl]-4-hydroxytetrahydro-2H-pyran-2-one | C19H28O4 | 详情 | 详情 | |
| (III) | 22647 | (4R,6R)-6-[2-[(1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydro-1-naphthalenyl]ethyl]-4-[[tert-butyl(dimethyl)silyl]oxy]tetrahydro-2H-pyran-2-one | C25H42O4Si | 详情 | 详情 | |
| (IV) | 22648 | 2,2-dimethylbutanoyl chloride | C6H11ClO | 详情 | 详情 | |
| (V) | 22649 | (1S,3R,7S,8S,8aR)-8-[2-((2R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-oxotetrahydro-2H-pyran-2-yl)ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate | C31H52O5Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The esterification of 6(R)-[2-(8(S)-hydroxy-2(S),6(R)-dimethyl-1,2,6,7,8,8a(R)-hexahydro-1(S)-naphthyl)ethyl]-4(R)-(tert-butyldimethylsilyloxy)tetrahydropyran-2-one (I) with 2,2-dimethylbutyric acid (II) by means of PPh3 and hexachloroethane in dichloromethane gives the protected intermediate (III), which is finally desilylated by means of Me-SO3H in water to yield the target simvastatin.
| 【1】 Kim, J.W.; Bae, H.; Lee, K.H.; Choi, K.D. (Cheil Jedang Corp.); A process for producing simvastatin. WO 0172734 . |
| 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) | 22647 | (4R,6R)-6-[2-[(1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydro-1-naphthalenyl]ethyl]-4-[[tert-butyl(dimethyl)silyl]oxy]tetrahydro-2H-pyran-2-one | C25H42O4Si | 详情 | 详情 | |
| (II) | 50845 | 2,2'-Dimethyl butyric acid; 2,2-Dimethylbutyric acid; Dimethylethylacetic acid | 595-37-9 | C6H12O2 | 详情 | 详情 |
| (III) | 22649 | (1S,3R,7S,8S,8aR)-8-[2-((2R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-oxotetrahydro-2H-pyran-2-yl)ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate | C31H52O5Si | 详情 | 详情 |