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【结 构 式】 
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【分子编号】40316 【品名】dimethyl (1R,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-3,5-dioxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8,8-dicarboxylate 【CA登记号】 |
【 分 子 式 】C37H54O8S2 【 分 子 量 】690.96296 【元素组成】C 64.32% H 7.88% O 18.52% S 9.28% |
合成路线1
该中间体在本合成路线中的序号：(XV)The condensation of 4-(ethylsulfanyl)-2-butynoic acid methyl ester (I) with the vinyl copper derivative (III) by means of DBU in THF gives the addition product (IV), which is treated with methyl chloroformate and LHMDS in THF yielding the malonic ester (V): The condensation of (V) with the chiral oxazolidinone (VI) by means of Cs2CO3 in acetonitrile affords the addition compound (VII), which is further condensed with the aldehyde (VIII) by means of Bu2B-OTf and TEA in dichloromethane giving the adduct (IX). The cyclization of (IX) by means of ZnCl2 and pyridine in dichloromethane yields the bicyclic compound (X), which is treated with allyl thioglycolate (XI) and LHMDS in ether producing the opening of the thiazolidinone ring. The resulting thiocarboxylic ester (XII) is submitted to cyclization by means of DBU in THF furnishing the tricyclic compound (XIII), which is selectively dehydrated and decarboxylated with Pd(OAc)2/PPh3 and pyr/Ac2O giving the tricyclic thiophenone (XIV). The oxidation of (XIV) with TBDMS-Cl, DBU and AgNO3 in hot DMSO affords the tricyclic thiophenedione (XV).
| 【1】 Waizumi, N.; et al.; Total synthesis of (-)-CP-263,114 (phomoidride B). J Am Chem Soc 2000, 122, 32, 7825. |
| 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) | 40302 | methyl 4-(propylsulfanyl)-2-butynoate | C8H12O2S | 详情 | 详情 | |
| (II) | 40303 | methyl 4-(propylsulfanyl)-2,3-butadienoate | C8H12O2S | 详情 | 详情 | |
| (III) | 40304 | (1E,8E)-1,8-decadienylcopper | C10H17Cu | 详情 | 详情 | |
| (IV) | 40305 | methyl (4E,11E)-3-[(E)-(propylsulfanyl)methylidene]-4,11-tridecadienoate | C18H30O2S | 详情 | 详情 | |
| (V) | 40306 | dimethyl 2-[(2E,9E)-1-[(Z)-(propylsulfanyl)methylidene]-2,9-undecadienyl]malonate | C20H32O4S | 详情 | 详情 | |
| (VI) | 40307 | (4S)-3-acryloyl-4-benzyl-1,3-oxazolidin-2-one | C13H13NO3 | 详情 | 详情 | |
| (VII) | 40308 | dimethyl 2-[3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxopropyl]-2-[(2E,9E)-1-[(E)-(propylsulfanyl)methylidene]-2,9-undecadienyl]malonate | C33H45NO7S | 详情 | 详情 | |
| (VIII) | 40309 | (E)-4-[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2-butenal | C13H22O3 | 详情 | 详情 | |
| (IX) | 40310 | dimethyl 2-[(2S,4E)-2-[[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-6-[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]-3-oxo-4-hexenyl]-2-[(2E,9E)-1-[(E)-(propylsulfanyl)methylidene]-2,9-undecadienyl]malonate | C46H65NO10S | 详情 | 详情 | |
| (X) | 40311 | dimethyl (4S,6R,7R,8R,10R)-4-[[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-7-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-8-[(E)-6-octenyl]-5-oxo-10-(propylsulfanyl)bicyclo[4.3.1]dec-1(9)-ene-2,2-dicarboxylate | C46H65NO10S | 详情 | 详情 | |
| (XI) | 40312 | allyl 2-sulfanylacetate | C5H8O2S | 详情 | 详情 | |
| (XII) | 40313 | dimethyl (4S,6R,7R,8R,10R)-4-([[2-(allyloxy)-2-oxoethyl]sulfanyl]carbonyl)-7-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-8-[(E)-6-octenyl]-5-oxo-10-(propylsulfanyl)bicyclo[4.3.1]dec-1(9)-ene-2,2-dicarboxylate | C41H62O10S2 | 详情 | 详情 | |
| (XIII) | 40314 | 3-allyl 8,8-dimethyl (1R,2R,3S,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-2-hydroxy-11-[(E)-6-octenyl]-5-oxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]tridec-9-ene-3,8,8-tricarboxylate | C41H62O10S2 | 详情 | 详情 | |
| (XIV) | 40315 | dimethyl (1R,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-5-oxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8,8-dicarboxylate | C37H56O7S2 | 详情 | 详情 | |
| (XV) | 40316 | dimethyl (1R,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-3,5-dioxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8,8-dicarboxylate | C37H54O8S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XV)The successive treatment of (XV) with LiOH and Ba(OH)2 caused selective hydrolyses of the thiomaleic group and the less hindered methyl ester, yielding finally monocarboxylic acid (XVI). The conventional Arndt-Eister (oxalyl chloride, diazomethane and silver benzoate/tert-butanol) was used to convert acid (XVI) into the homologated ester (XVII). Careful oxidation of the sulfanyl group of (XVII) with MCPBA followed by a treatment with trifluoroacetic anhydride yields the ketone (XVIII), which is hydrolyzed and cyclized by means of 80% AcOH affording the cyclic acetal (XIX). Finally, this compound is oxidized with Jones reagent and the tert-butyl ester is deprotected with formic acid to provide the target compound.
| 【1】 Waizumi, N.; et al.; Total synthesis of (-)-CP-263,114 (phomoidride B). J Am Chem Soc 2000, 122, 32, 7825. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 40316 | dimethyl (1R,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-3,5-dioxo-13-(propylsulfanyl)-4-thiatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8,8-dicarboxylate | C37H54O8S2 | 详情 | 详情 | |
| (XVI) | 40317 | (1R,8R,11R,12R,13R)-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-8-(methoxycarbonyl)-11-[(E)-6-octenyl]-3,5-dioxo-13-(propylsulfanyl)-4-oxatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8-carboxylic acid | C36H52O9S | 详情 | 详情 | |
| (XVII) | 40318 | methyl (1R,8S,11R,12R,13R)-8-[2-(tert-butoxy)-2-oxoethyl]-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-3,5-dioxo-13-(propylsulfanyl)-4-oxatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8-carboxylate | C41H62O9S | 详情 | 详情 | |
| (XVIII) | 40319 | methyl (1R,8S,11R,12R)-8-[2-(tert-butoxy)-2-oxoethyl]-12-[[(4S,5S)-5-butyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-11-[(E)-6-octenyl]-3,5,13-trioxo-4-oxatricyclo[7.3.1.0(2,6)]trideca-2(6),9-diene-8-carboxylate | C38H54O10 | 详情 | 详情 | |
| (XIX) | 40320 | tert-butyl 2-[(2R,12R,13S,14R,15S)-14-butyl-15-(hydroxymethyl)-12-[(E)-6-octenyl]-4,6,18-trioxo-5,16,17-trioxapentacyclo[7.7.2.0(1,10).0(2,13).0(3,7)]octadeca-3(7),10-dien-9-yl]acetate | C34H46O9 | 详情 | 详情 |