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【结 构 式】 
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【分子编号】41782 【品名】2,2,2-trichloroethyl [(1S,2S,13R,15R,16R)-5-(allyloxy)-15-cyano-22-hydroxy-21-methoxy-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-13-yl]methylcarbamate 【CA登记号】 |
【 分 子 式 】C32H35Cl3N4O7 【 分 子 量 】694.01076 【元素组成】C 55.38% H 5.08% Cl 15.33% N 8.07% O 16.14% |
合成路线1
该中间体在本合成路线中的序号：(IX)Reaction of cyanosafracin B (I) with Boc2O in ethanol gives the amino-protected compound (II), which is treated with methoxymethyl bromide (MOM-Br), DIEA and DMAP in acetonitrile yielding the O-protected compound (III). The demethylation of (III) with NaOH in methanol affords the hydroxyquinone (IV), which is reduced with H2 over Pd/C and cyclized with bromochloromethane and Cs2CO3 in hot DMF to provide compound (V). Reaction of (V) with allyl bromide (VI) and Cs2CO3 in DMF gives the allyl ether (VII), which first is treated with TFA, phenyl isothiocyanate and HCl to yield the primary amine (VIII) and then protected at the free NH2 group with Troc-Cl and pyridine, to afford the amino protected compound (IX).
| 【1】 Cuevas, C.; Martin, M.J.; Perez, M.; et al.; Synthesis of ecteinascidin ET-743 and phathalascidin Pt-650 from cyanosafracin B. Org Lett 2000, 2, 16, 2545. |
| 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) | 41775 | (2S)-2-amino-N-[[(1S,2S,10R,12R,13R)-12-cyano-19-hydroxy-7,18-dimethoxy-6,17,21-trimethyl-5,8-dioxo-11,21-diazapentacyclo[11.7.1.0(2,11).0(4,9).0(15,20)]henicosa-4(9),6,15,17,19-pentaen-10-yl]methyl]propanamide | C29H35N5O6 | 详情 | 详情 | |
| (II) | 41776 | tert-butyl (1S)-2-([[(1S,2S,10R,12R,13R)-12-cyano-19-hydroxy-7,18-dimethoxy-6,17,21-trimethyl-5,8-dioxo-11,21-diazapentacyclo[11.7.1.0(2,11).0(4,9).0(15,20)]henicosa-4(9),6,15,17,19-pentaen-10-yl]methyl]amino)-1-methyl-2-oxoethylcarbamate | C34H43N5O8 | 详情 | 详情 | |
| (III) | 41777 | tert-butyl (1S)-2-([[(1S,2S,10R,12R,13R)-12-cyano-7,18-dimethoxy-19-(methoxymethoxy)-6,17,21-trimethyl-5,8-dioxo-11,21-diazapentacyclo[11.7.1.0(2,11).0(4,9).0(15,20)]henicosa-4(9),6,15,17,19-pentaen-10-yl]methyl]amino)-1-methyl-2-oxoethylcarbamate | C36H47N5O9 | 详情 | 详情 | |
| (IV) | 41778 | tert-butyl (1S)-2-([[(1S,2S,10R,12R,13R)-12-cyano-7-hydroxy-18-methoxy-19-(methoxymethoxy)-6,17,21-trimethyl-5,8-dioxo-11,21-diazapentacyclo[11.7.1.0(2,11).0(4,9).0(15,20)]henicosa-4(9),6,15,17,19-pentaen-10-yl]methyl]amino)-1-methyl-2-oxoethylcarba | C35H45N5O9 | 详情 | 详情 | |
| (V) | 41779 | tert-butyl (1S)-2-([[(1S,2S,13R,15R,16R)-15-cyano-5-hydroxy-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-13-yl]methyl]amino)-1-methyl-2-oxoe | C36H47N5O9 | 详情 | 详情 | |
| (VI) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (VII) | 41780 | tert-butyl (1S)-2-([[(1S,2S,13R,15R,16R)-5-(allyloxy)-15-cyano-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-13-yl]methyl]amino)-1-methyl-2-o | C39H51N5O9 | 详情 | 详情 | |
| (VIII) | 41781 | (1S,2S,13R,15R,16R)-5-(allyloxy)-13-(aminomethyl)-22-hydroxy-21-methoxy-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaene-15-carbonitrile | C29H34N4O5 | 详情 | 详情 | |
| (IX) | 41782 | 2,2,2-trichloroethyl [(1S,2S,13R,15R,16R)-5-(allyloxy)-15-cyano-22-hydroxy-21-methoxy-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-13-yl]methylcarbamate | C32H35Cl3N4O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Reaction of (IX) with MOM-Br and DIEA as before affords the ether (X), which is treated with Zn/HOAc in order to regenerate the primary amino group giving (XI). The reaction of (XI) with NaNO2 and HOAc eliminates the NH2 group, affording the primary alcohol (XII), which is esterified with the protected (S)-cysteine (XIII) by means of EDC and DMAP in dichloromethane furnishing the cysteine ester (XIV). Reaction of (XIV) with Bu3SnH and PdCl2(PPh3)2, followed by oxidation with (PhSeO)2O in dichloromethane gives the hydroxyketone (XV), which is cyclized with Tf2O and Ac2O yielding the heptacyclic compound (XVI). Elimination of the MOM protecting group with TMSCl and NaI in CH3CN/CH2Cl2 affords the phenolic compound (XVII).
| 【1】 Cuevas, C.; Martin, M.J.; Perez, M.; et al.; Synthesis of ecteinascidin ET-743 and phathalascidin Pt-650 from cyanosafracin B. Org Lett 2000, 2, 16, 2545. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 41782 | 2,2,2-trichloroethyl [(1S,2S,13R,15R,16R)-5-(allyloxy)-15-cyano-22-hydroxy-21-methoxy-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-13-yl]methylcarbamate | C32H35Cl3N4O7 | 详情 | 详情 | |
| (X) | 41783 | 2,2,2-trichloroethyl [(1S,2S,13R,15R,16R)-5-(allyloxy)-15-cyano-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-13-yl]methylcarbamate | C34H39Cl3N4O8 | 详情 | 详情 | |
| (XI) | 41784 | (1S,2S,13R,15R,16R)-5-(allyloxy)-13-(aminomethyl)-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaene-15-carbonitrile | C31H38N4O6 | 详情 | 详情 | |
| (XII) | 41785 | (1S,2S,13R,15R,16R)-5-(allyloxy)-13-(hydroxymethyl)-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaene-15-carbonitrile | C31H37N3O7 | 详情 | 详情 | |
| (XIII) | 41786 | (2S)-3-[(9H-fluoren-9-ylmethyl)sulfanyl]-2-[[(2,2,2-trichloroethoxy)carbonyl]amino]propionic acid | C20H18Cl3NO4S | 详情 | 详情 | |
| (XIV) | 41787 | [(1S,2S,13R,15R,16R)-5-(allyloxy)-15-cyano-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-13-yl]methyl (2S)-3-[(9H-fluoren-9-ylmethyl)sulfanyl | C51H53Cl3N4O10S | 详情 | 详情 | |
| (XV) | 41788 | C48H49Cl3N4O11S | 详情 | 详情 | ||
| (XVI) | 41789 | C36H39Cl3N4O11S | 详情 | 详情 | ||
| (XVII) | 41790 | C34H35Cl3N4O10S | 详情 | 详情 |