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【结 构 式】 
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【分子编号】38861 【品名】4-Methoxybenzenemethanol; (4-methoxyphenyl)methanol; 4-Methoxybenzyl alcohol; Anis alcohol; Anisyl Alcohol; 4-Anisic Alcohol; p-Anisyl alcohol; Anise alcohol 【CA登记号】105-13-5 |
【 分 子 式 】C8H10O2 【 分 子 量 】138.1662 【元素组成】C 69.55% H 7.3% O 23.16% |
合成路线1
该中间体在本合成路线中的序号：(II)p-Methoxybenzyl itaconate (III) was prepared by reaction of itaconic anhydride (I) with p-methoxybenzyl alcohol (II) at 55-60 C (1). Condensation of the lithium enolate of (III) with nonanal (IV) in THF at -78 C gave adduct (V), which upon treatment with trifluoroacetic acid underwent cyclization and benzyl ester deprotection to yield the corresponding butyrolactone as a diastereomeric mixture. The major trans isomer was finally isolated by flash chromatography.
| 【1】 Mani, N.S.; Li, J.N.; Frehywot, G.; Pizer, E.S.; Kuhajda, F.P.; Townsend, G.A.; Syntesis and antitumor activity of an inhibitor fatty acid synthase. Proceedings of the National Academy of Sciences of the United States of America 2000, 97, 7, 3450. |
| 【2】 Kuhajda, F.P.; Mani, N.S.; Pasternack, G.R.; Townsend, C.A. (Johns Hopkins University); Inhibition of fatty acid synthase as a means to reduce adipocyte mass. WO 9718806 . |
| 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) | 12891 | 3-Methylenedihydro-2,5-furandione; Itaconic anhydride | 2170-03-8 | C5H4O3 | 详情 | 详情 |
| (II) | 38861 | 4-Methoxybenzenemethanol; (4-methoxyphenyl)methanol; 4-Methoxybenzyl alcohol; Anis alcohol; Anisyl Alcohol; 4-Anisic Alcohol; p-Anisyl alcohol; Anise alcohol | 105-13-5 | C8H10O2 | 详情 | 详情 |
| (III) | 38862 | 2-[2-[(4-methoxybenzyl)oxy]-2-oxoethyl]acrylic acid | C13H14O5 | 详情 | 详情 | |
| (IV) | 38863 | nonanal | 124-19-6 | C9H18O | 详情 | 详情 |
| (V) | 38864 | 2-(2-hydroxy-1-[[(4-methoxybenzyl)oxy]carbonyl]decyl)acrylic acid | C22H32O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)In an alternative procedure, 2,2-dimethylsuccinic anhydride (II) was reacted with p-methoxybenzyl alcohol (V) in the presence of dicyclohexylamine to afford the beta,beta-dimethyl p-methoxybenzyl ester (VI) as the major product, along with minor amounts of the alpha,alpha-dimethyl regioisomer. Condensation of hemiester (VI) with AZT (IV) by using DCC and DMAP produced diester (VII). The p-methoxybenzyl group of (VII) was then removed by treatment with trifluoroacetic acid to give (VIII). Acid (VIII) was finally coupled with the dipeptide amide (I) in the presence of BOP and HOBt.
| 【1】 Kimura, T.; Matsuda, T.; Akaji, K.; Kiso, Y.; Matsumoto, H.; Hamawaki, T.; Synthesis and activity of a new type of anti-HIV agents, conjugate of HIV protease inhibitor with reverse transcriptase inhibitor. Pept Sci 1999, 305. |
| 【2】 Kimura, T.; Kiso, Y.; Matsumoto, H.; Akaji, K.; Hamawaki, T.; Matsuda, T.; A new class of anti-HIV agents: Synthesis and activity of conjugates of HIV protease inhibitors with a reverse transcriptase inhibitor. Bioorg Med Chem Lett 1999, 9, 6, 803. |
| 【3】 Mitoguchi, T.; Kiso, Y.; Nakata, S.; Hayashi, Y.; Matsuda, T.; Matsumoto, H.; Kimura, T.; Synthesis and biological evaluation of prodrug-type anti-HIV agents. Ester conjugates of carboxylic acid-containing dipeptide HIV protease inhibitors and a reverse transcriptase inhibitor. Bioorg Med Chem 2001, 9, 2, 417. |
| 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) | 51181 | (4R)-3-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-N-(2-methylbenzyl)-1,3-thiazolidine-4-carboxamide | C24H31N3O3S | 详情 | 详情 | |
| (II) | 29295 | 3,3-dimethyldihydro-2,5-furandione | 17347-61-4 | C6H8O3 | 详情 | 详情 |
| (IV) | 25317 | 1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | 101703-35-9 | C10H13N5O4 | 详情 | 详情 |
| (V) | 38861 | 4-Methoxybenzenemethanol; (4-methoxyphenyl)methanol; 4-Methoxybenzyl alcohol; Anis alcohol; Anisyl Alcohol; 4-Anisic Alcohol; p-Anisyl alcohol; Anise alcohol | 105-13-5 | C8H10O2 | 详情 | 详情 |
| (VI) | 51183 | 4-[(4-methoxybenzyl)oxy]-2,2-dimethyl-4-oxobutyric acid | C14H18O5 | 详情 | 详情 | |
| (VII) | 51184 | 1-([(2S,3S,5R)-3-azido-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl) 4-(4-methoxybenzyl) 2,2-dimethylsuccinate | C24H29N5O8 | 详情 | 详情 | |
| (VIII) | 51185 | 4-([(2S,3S,5R)-3-azido-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methoxy)-3,3-dimethyl-4-oxobutyric acid | C16H21N5O7 | 详情 | 详情 |