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【结 构 式】 
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【分子编号】60326 【品名】(1R,2S,4R,5R,8R,9S)-9-formyl-2-[({(2R,3S,4S,5R,6R)-4-[(2Z,4E)-2,4-hexadienoyloxy]-3-hydroxy-5-methoxy-6-methyltetrahydro-2H-pyran-2-yl}oxy)methyl]-13-isopropyl-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylic acid 【CA登记号】 |
【 分 子 式 】C33H46O9 【 分 子 量 】586.72284 【元素组成】C 67.56% H 7.9% O 24.54% |
合成路线1
该中间体在本合成路线中的序号：(I)The hydrolysis of Zofimarin (I) with NaOMe in methanol gives the sodium salt of the deacylated compound (II), which is treated with Pmb-Cl in DMF to yield the p-methoxybenzyl ester (III). The protection of the formyl group of (III) by means of ethyleneglycol, trimethyl orthoformate and TsOH affords the ethylene ketal (IV), which is oxidized at the vicinal diol group by means of NaIO4 in methanol/water to provide the dialdehyde (V). The reductocyclization of (V) with allylamine (VI) by means of NaBH3CN and AcOH in acetonitrile leads to the perhydro oxazepine derivative (VII), which is deallylated by means of Rh(PPh3)3Cl in aqueous ethanol to give compound (VIII). The alkylation of (VIII) with 2-methylallyl bromide (IX) by means of NaHCO3 and NaI in ethanol yields the protected precursor (X), which is finally treated with TFA in dichloromethane to provide the target zofimarin derivative.
| 【1】 Fukuoka, T.; Kamai, Y.; Kakuta, M.; Kaneko, S.; Arai, M.; Uchida, T.; Konosu, T.; Kuwahara, S.; Design, synthesis, and in vitro activity of RS-135853, a novel zofimarin-related antifungal agent. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-824. |
| 【2】 Kaneko, S.; Uchida, T.; Arai, M.; Kounosu, T. (Sankyo Co., Ltd.); Zofimarin derivs. having an oxazepan ring. JP 2002161086; WO 0223541 . |
| 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) | 60326 | (1R,2S,4R,5R,8R,9S)-9-formyl-2-[({(2R,3S,4S,5R,6R)-4-[(2Z,4E)-2,4-hexadienoyloxy]-3-hydroxy-5-methoxy-6-methyltetrahydro-2H-pyran-2-yl}oxy)methyl]-13-isopropyl-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylic acid | C33H46O9 | 详情 | 详情 | |
| (II) | 59613 | (1R,2S,4R,5R,8R,9S,11R)-2-({[(2R,3S,4S,5S,6R)-3,4-dihydroxy-5-methoxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}methyl)-9-formyl-13-isopropyl-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylic acid | C27H40O8 | 详情 | 详情 | |
| (III) | 60327 | 4-methoxybenzyl (1R,2S,4R,5R,8R,9S)-2-({[(2R,3S,4S,5S,6R)-3,4-dihydroxy-5-methoxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}methyl)-9-formyl-13-isopropyl-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylate | C35H48O9 | 详情 | 详情 | |
| (IV) | 60328 | 4-methoxybenzyl (1R,2S,4R,5R,8R,9S)-2-({[(2R,3S,4S,5S,6R)-3,4-dihydroxy-5-methoxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}methyl)-9-(1,3-dioxolan-2-yl)-13-isopropyl-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylate | C37H52O10 | 详情 | 详情 | |
| (V) | 60329 | 4-methoxybenzyl (1R,2S,4R,5R,8R,9S)-9-(1,3-dioxolan-2-yl)-13-isopropyl-2-{[((1R)-1-{[(1R,2R)-2-methoxy-1-methyl-3-oxopropyl]oxy}-2-oxoethyl)oxy]methyl}-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylate | C37H50O10 | 详情 | 详情 | |
| (VI) | 13672 | Allylamine; 2-Propen-1-amine | 107-11-9 | C3H7N | 详情 | 详情 |
| (VII) | 60330 | 4-methoxybenzyl (1R,2S,4R,5R,8R,9S)-2-({[(2R,6S,7R)-4-allyl-6-methoxy-7-methyl-1,4-oxazepan-2-yl]oxy}methyl)-9-(1,3-dioxolan-2-yl)-13-isopropyl-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylate | C40H57NO8 | 详情 | 详情 | |
| (VIII) | 60331 | 4-methoxybenzyl (1R,2S,4R,5R,8R,9S)-9-(1,3-dioxolan-2-yl)-13-isopropyl-2-({[(2R,6S,7R)-6-methoxy-7-methyl-1,4-oxazepan-2-yl]oxy}methyl)-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylate | C37H53NO8 | 详情 | 详情 | |
| (IX) | 40015 | 3-bromo-2-methyl-1-propene | 1458-98-6 | C4H7Br | 详情 | 详情 |
| (X) | 60332 | 4-methoxybenzyl (1R,2S,4R,5R,8R,9S)-9-(1,3-dioxolan-2-yl)-13-isopropyl-2-({[(2R,6S,7R)-6-methoxy-7-methyl-4-(2-methyl-2-propenyl)-1,4-oxazepan-2-yl]oxy}methyl)-5-methyltetracyclo[7.4.0.0~2,11~.0~4,8~]tridec-12-ene-1-carboxylate | C41H59NO8 | 详情 | 详情 |