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【结 构 式】 
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【分子编号】47423 【品名】[(8R,9S,10S,12S)-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-9-hydroxy-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-8-yl]methyl carbamate 【CA登记号】 |
【 分 子 式 】C36H37N3O9S 【 分 子 量 】687.7706 【元素组成】C 62.87% H 5.42% N 6.11% O 20.94% S 4.66% |
合成路线1
该中间体在本合成路线中的序号：(LV)The reduction of the carbonyl group of (XLIV) with NaBH4 in THF gives the diol (XLV), which is selectively silylated at the primary OH group with Tbdps-Cl, TEA and DMAP, yielding silyl ether (XLVI). Elimination of the Alloc protecting group with Pd(PPh3)4, PPh3 in THF affords compound (XLVII), which is carefully oxidized at the NH group with MCPBA in dichloromethane, providing the hydroyamine (XLVIII). The reaction of (XLVIII) with Ac2O gives the acetate (XLIX), which is oxidized with DMP to yield the ketone (L). The desilylation of (L) with HF and pyridine affords the hydroxyketone (LI), which by treatment with K2CO3 in methanol undergoes cyclization to the tetracyclic compound (LIII) through the intermediate dihydroxyketone (LII). The reaction of (LIII) with diphosgene and pyridine gives the cyclic carbonate (LIV), which is treated with ammonia in THF, yielding the carbamic ester (LV).
| 【1】 Katoh, T.; Terashima, S.; Total synthesis of antitumor antibiotic FR900482. Yuki Gosei Kagaku Kyokaishi 1997, 55, 11, 946. |
| 【2】 Katoh, T.; et al.; Total synthesis of natural (+)-FR900482. 3. Completion of the synthesis. Tetrahedron Lett 1996, 37, 20, 3479. |
| 【3】 Katoh, T.; et al.; Total synthesis of an enantiomeric pair of FR900482. 3. Completion of the synthesis by assembling the two segments. Tetrahedron 1997, 53, 30, 10253. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLIV) | 47412 | allyl (1aS,8R,9aS)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]-9-oxo-1,1a,2,8,9,9a-hexahydro-3H-azireno[2,3-c][1]benzazocine-3-carboxylate | C39H40N2O9S | 详情 | 详情 | |
| (XLV) | 47413 | allyl (1aS,8R,9R,9aS)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-9-hydroxy-8-(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]-1,1a,2,8,9,9a-hexahydro-3H-azireno[2,3-c][1]benzazocine-3-carboxylate | C39H42N2O9S | 详情 | 详情 | |
| (XLVI) | 47414 | allyl (1aS,8R,9R,9aS)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-([[tert-butyl(diphenyl)silyl]oxy]methyl)-9-hydroxy-1-[(4-methylphenyl)sulfonyl]-1,1a,2,8,9,9a-hexahydro-3H-azireno[2,3-c][1]benzazocine-3-carboxylate | C55H60N2O9SSi | 详情 | 详情 | |
| (XLVII) | 47415 | (1aS,8R,9R,9aS)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-([[tert-butyl(diphenyl)silyl]oxy]methyl)-1-[(4-methylphenyl)sulfonyl]-1a,2,3,8,9,9a-hexahydro-1H-azireno[2,3-c][1]benzazocin-9-ol | C51H56N2O7SSi | 详情 | 详情 | |
| (XLVIII) | 47416 | (1aS,8R,9R,9aS)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-([[tert-butyl(diphenyl)silyl]oxy]methyl)-1-[(4-methylphenyl)sulfonyl]-1,1a,2,8,9,9a-hexahydro-3H-azireno[2,3-c][1]benzazocine-3,9-diol | C51H56N2O8SSi | 详情 | 详情 | |
| (XLIX) | 47417 | (1aS,8R,9R,9aS)-3-(acetoxy)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-([[tert-butyl(diphenyl)silyl]oxy]methyl)-1-[(4-methylphenyl)sulfonyl]-1a,2,3,8,9,9a-hexahydro-1H-azireno[2,3-c][1]benzazocin-9-ol | C53H58N2O9SSi | 详情 | 详情 | |
| (L) | 47418 | (1aS,8R,9aS)-3-(acetoxy)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-([[tert-butyl(diphenyl)silyl]oxy]methyl)-1-[(4-methylphenyl)sulfonyl]-1,1a,2,3,8,9a-hexahydro-9H-azireno[2,3-c][1]benzazocin-9-one | C53H56N2O9SSi | 详情 | 详情 | |
| (LI) | 47419 | (1aS,8R,9aS)-3-(acetoxy)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-8-(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]-1,1a,2,3,8,9a-hexahydro-9H-azireno[2,3-c][1]benzazocin-9-one | C37H38N2O9S | 详情 | 详情 | |
| (LII) | 47420 | (1aS,8R,9aS)-7-(benzyloxy)-5-[[(benzyloxy)methoxy]methyl]-3-hydroxy-8-(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]-1,1a,2,3,8,9a-hexahydro-9H-azireno[2,3-c][1]benzazocin-9-one | C35H36N2O8S | 详情 | 详情 | |
| (LIII) | 47421 | (8R,9S,10S,12S)-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-8-(hydroxymethyl)-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-ol | C35H36N2O8S | 详情 | 详情 | |
| (LIV) | 47422 | (1S,6R,15S,17S)-8-(benzyloxy)-10-[[(benzyloxy)methoxy]methyl]-16-[(4-methylphenyl)sulfonyl]-2,4,18-trioxa-13,16-diazapentacyclo[11.4.1.0(1,6).0(7,12).0(15,17)]octadeca-7,9,11-trien-3-one | C36H34N2O9S | 详情 | 详情 | |
| (LV) | 47423 | [(8R,9S,10S,12S)-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-9-hydroxy-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-8-yl]methyl carbamate | C36H37N3O9S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LV)The reaction of (LV) with Ac2O and pyridine gives the acetate (LVI), which is detosylated with sodium naphthalenide in DME to yield compound (LVII). The hydrogenation of (LVII) with H2 over Pd/C in ethyl acetate eliminates the Bn and Bom protecting groups to afford dihydroxy compound (LVIII), which is oxidized at the carbinol group with oxalyl chloride to provide the aldehyde (LIX). Finally, the cleavage of the acetoxy group of (LIX) with ammonia in methanol furnishes the target compound.
| 【1】 Katoh, T.; Terashima, S.; Total synthesis of antitumor antibiotic FR900482. Yuki Gosei Kagaku Kyokaishi 1997, 55, 11, 946. |
| 【2】 Katoh, T.; et al.; Total synthesis of an enantiomeric pair of FR900482. 3. Completion of the synthesis by assembling the two segments. Tetrahedron 1997, 53, 30, 10253. |
| 【3】 Katoh, T.; et al.; Total synthesis of natural (+)-FR900482. 3. Completion of the synthesis. Tetrahedron Lett 1996, 37, 20, 3479. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LV) | 47423 | [(8R,9S,10S,12S)-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-9-hydroxy-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-8-yl]methyl carbamate | C36H37N3O9S | 详情 | 详情 | |
| (LVI) | 47424 | (8R,10S,12S)-8-[[(aminocarbonyl)oxy]methyl]-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-11-[(4-methylphenyl)sulfonyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-yl acetate | C38H39N3O10S | 详情 | 详情 | |
| (LVII) | 47425 | (8R,10S,12S)-8-[[(aminocarbonyl)oxy]methyl]-6-(benzyloxy)-4-[[(benzyloxy)methoxy]methyl]-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-yl acetate | C31H33N3O8 | 详情 | 详情 | |
| (LVIII) | 47426 | (8R,10S,12S)-8-[[(aminocarbonyl)oxy]methyl]-6-hydroxy-4-(hydroxymethyl)-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-yl acetate | C16H19N3O7 | 详情 | 详情 | |
| (LIX) | 47427 | (8R,10S,12S)-8-[[(aminocarbonyl)oxy]methyl]-4-formyl-6-hydroxy-14-oxa-1,11-diazatetracyclo[7.4.1.0(2,7).0(10,12)]tetradeca-2,4,6-trien-9-yl acetate | C16H17N3O7 | 详情 | 详情 |