|
【结 构 式】 
|
【药物名称】Tretinoin;Solage 【化学名称】Vitamin a Acid;Vitinoin;Claravis;Retin-A;Aberel 【CA登记号】302-79-4 【 分 子 式 】C20H28O2 【 分 子 量 】300.44496 |
【开发单位】Bristol-Myers Squibb 【药理作用】Acne Therapy；DERMATOLOGIC DRUGS, Retinoids |
合成路线1
| 【1】 D Lera AR, Torrado A, Iglesias B,et aL. 1992. Stereospecifc synthesis of 9-demethylretinoids via palladium-catalyzed vinylboronic acid-vinyl iodide cross coupling. Tetrahedro Lett. 33 (41): 6205～6208 |
| 【2】 Dominguez B,Iglesias B, de Lera Angle R. 1998. Tetnenylstannanes in the synthesis of retinoic acid anld its ring-modlified analogues. J Org Chem. 63. 4135～4139 |
| 【3】 Pazas Y, Iglesias B, de Lera Angel R. 2001. The Suzuki coupling reaction in the stereocontrolled synthesis of 9-cis-retinoic acid and its ring-demethylated anaIoguer. J Ore Chem，66(25): 8483～8489（有关9-顺式一维A酸及其衍生物的合成） |
| 【4】 Trost BM, Sorum MT, Chan C. et aL. 1997. Palladium-catalyzed additions of terminal alkynes to acceptor alkynes, J Am Chem Soc, 119: 698～708 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 66891 | (2E,4E,6E,8E)-ethyl 3,7-dimethyl-9-(tributylstannyl)nona-2,4,6,8-tetraenoate | C25H44O2Sn | 详情 | 详情 | |
| (I) | 65494 | 2,2,6-Trimethylcyclohexanone | C9H15O | 详情 | 详情 | |
| (II) | 66889 | 2,6,6-trimethylcyclohex-1-en-1-yl trifluoromethanesulfonate | C10H15F3O3S | 详情 | 详情 | |
| (III) | 65492 | C18H34OSn | 详情 | 详情 | ||
| (IV) | 44704 | ethyl (E)-4-(diethoxyphosphoryl)-3-methyl-2-butenoate | 41891-54-7 | C11H21O5P | 详情 | 详情 |
合成路线2
| 【1】 Abarbri M, Parrain J-L, Duchtne A, et aL. 2006, Stereoselective synthesis of trienoic acid: synthesis of retinoic acids and analogues. Synthesis, (17): 2951～2970 |
| 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) | 39584 | (E)-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-buten-2-one | 14901-07-6 | C13H20O | 详情 | 详情 |
| (II) | 65501 | 73395-75-2 | C13H18 | 详情 | 详情 | |
| (III) | 66892 | tributyl((1E,3E)-2-methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)buta-1,3-dien-1-yl)stannane | C26H48Sn | 详情 | 详情 | |
| (IV) | 66893 | (2E,4E)-5-iodo-3-methylpenta-2,4-dienoic acid | C6H7IO2 | 详情 | 详情 |
合成路线3
| 【1】 Jeon H-Y, Yeo JE, Jeong YC, et aL. 2004. Stereoselective and convergent syntheses of retinoic acid and its ester derivatives by the sulfone olefination reaction. Synthesis, (17): 2813～2820 |
| 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) | 66894 | (((2E,4E)-3-methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)penta-2,4-dien-1-yl)sulfonyl)benzene | C21H28O2S | 详情 | 详情 | |
| (II) | 66895 | diethyl 2-(1-bromopropan-2-ylidene)malonate | C10H15BrO4 | 详情 | 详情 | |
| (III) | 66896 | diethyl 2-((5E,7E)-6-methyl-4-(phenylsulfonyl)-8-(2,6,6-trimethylcyclohex-1-en-1-yl)octa-5,7-dien-2-ylidene)malonate | C31H42O6S | 详情 | 详情 | |
| (IV) | 66897 | 2-((5E,7E)-6-methyl-4-(phenylsulfonyl)-8-(2,6,6-trimethylcyclohex-1-en-1-yl)octa-5,7-dien-2-ylidene)malonic acid | C27H34O6S | 详情 | 详情 |
合成路线4
| 【1】 Wada A, Fukunaga K, Ito M, et aL. 2004. Preparation and biological activity of 13-substituted retinoic acids. Bioorg Med Chem, 12 (14): 393～3942 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 65481 | (2E,4E)-3-Methyl-5-(2,6,6-Trimethyl-1-Cyclohexenyl)Penta-2,4-Dienal | 1209-68-3 | C15H22O | 详情 | 详情 |
| (I) | 66898 | (E)-1,3,3-trimethyl-2-(3-((trifluoromethyl)sulfonyl)prop-1-en-1-yl)cyclohex-1-ene | C13H19F3O2S | 详情 | 详情 | |
| (II) | 66899 | (E)-3-(tributylstannyl)but-2-en-1-ol | C16H34OSn | 详情 | 详情 | |
| (III) | 33333 | (2E,4E)-3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadien-1-ol | 3917-39-3 | C15H24O | 详情 | 详情 |
| (VI) | 66900 | 1,3,3-trimethyl-2-((1E,3E)-3-methylhexa-1,3-dien-5-yn-1-yl)cyclohex-1-ene | C16H22 | 详情 | 详情 | |
| (VII) | 66901 | (2E,4E,6E,8E)-ethyl 3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate | C22H32O2 | 详情 | 详情 |
合成路线5
| 【1】 Cartier D, Valla A, Le Guillou R, et al. 2003. New, regiaselective, one-pot synthesis of (all-E) -retinoic acid and analogues from enaminodiester synthons. Eur J Org Chem, (12). 2250～2253 |
| 【2】 Cartier D, Valla A, Labia R, et al. 2003. A new one-pot synthesis of all E-retinoic acid via a new enamin odiester synthon. Tetrahedrcm Lett, 44 (31): 5789～5790 |
| 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) | 49671 | dimethyl 2-(1-methylethylidene)malonate | 22035-53-6 | C8H12O4 | 详情 | 详情 |
| (V) | 66904 | dimethyl 2-((2E,4E,6E,8Z)-6-methyl-8-(2,6,6-trimethylcyclohex-2-en-1-ylidene)octa-2,4,6-trien-2-yl)malonate | C23H32O4 | 详情 | 详情 | |
| (II) | 66902 | (E)-dimethyl 2-(4-(dimethylamino)but-3-en-2-ylidene)malonate | C11H17NO4 | 详情 | 详情 | |
| (III) | 39584 | (E)-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-buten-2-one | 14901-07-6 | C13H20O | 详情 | 详情 |
| (IV) | 66903 | dimethyl 2-((2E,4E,7E)-6-oxo-8-(2,6,6-trimethylcyclohex-1-en-1-yl)octa-2,4,7-trien-2-yl)malonate | C22H30O5 | 详情 | 详情 |
合成路线6
| 【1】 Valla A, Andriamialisoa Z, Prat V, et aL. 2000. Stereoselective synthesis of 13E and 132 retinoic acids via a novelintermediate-methylenealdehyde at 0-15. Tetrahedron, 56 (37): 7211～7215 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 49671 | dimethyl 2-(1-methylethylidene)malonate | 22035-53-6 | C8H12O4 | 详情 | 详情 |
| (I) | 66905 | (E)-5,5-dimethoxy-1-(2,6,6-trimethylcyclohex-1-en-1-yl)pent-1-en-3-one | C16H26O3 | 详情 | 详情 | |
| (II) | 66906 | (E)-2-(5,5-dimethoxy-3-methylenepent-1-en-1-yl)-1,3,3-trimethylcyclohex-1-ene | C17H28O2 | 详情 | 详情 | |
| (III) | 66907 | (E)-3-methylene-5-(2,6,6-trimethylcyclohex-1-en-1-yl)pent-4-enal | C15H22O | 详情 | 详情 |
Extended Information