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【结 构 式】 
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【分子编号】11218 【品名】2,2,2-trichloroethyl (1R,3S)-3-[(2R,3R,5S)-1-[(benzyloxy)carbonyl]-5-[(benzyloxy)methyl]-3-[(methoxymethoxy)methyl]pyrrolidinyl]-8-methoxy-1-[(4S,5S)-5-[(methoxymethoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C44H55Cl3N2O12 【 分 子 量 】910.28508 【元素组成】C 58.06% H 6.09% Cl 11.68% N 3.08% O 21.09% |
合成路线1
该中间体在本合成路线中的序号：(X)A new total synthesis of (-)-quinocarcin has been reported: The condensation of 2-bromo-3-methylanisole (I) with 4-O-benzyl-2,3-O-isopropylidene-D-threose (II) by means of butyllithium in ether followed by oxidation with CrO3-pyridine gives the ketone (III), which is debenzylated by hydrogenation over Pd(OH)2 to yield the ketol (IV). The protection of the hydroxy group of (IV) with methoxymethyl chloride affords the fully protected ketone (V), which is condensed with suitable optically active pyrrolidine (VI) by means of lithium diisopropylamide, followed by oxidation with CrO3-H2SO4 to give the diketone (VII). The cyclization of (VII) with ammonia in THF yields the isoquinoline (VIII), which is reduced with sodium cyanoborohydride to the tetrahydro derivative (IX). The protection of the imino group of (IX) with 2,2,2-trichloroethyl chloroformate yields the trichloroethyl ester (X).
| 【1】 Katoh, T.; Minami, J.; Kirihara, M.; Kobayashi, Y.; Arai, K.; Nagata, Y.; Terashima, S.; Total synthesis of (-)-quinocarcin and (-)-10-decarboxyquinocarcin. Tetrahedron Lett 1993, 34, 36, 5747. |
| 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) | 11209 | 2-Bromo-1-methoxy-3-methylbenzene; 2-Bromo-3-methylphenyl methyl ether | C8H9BrO | 详情 | 详情 | |
| (II) | 11210 | (4R,5S)-5-[(Benzyloxy)methyl]-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde | C14H18O4 | 详情 | 详情 | |
| (III) | 11211 | (4R,5S)-5-[(Benzyloxy)methyl]-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde | C22H26O5 | 详情 | 详情 | |
| (IV) | 11212 | [(4R,5S)-5-(Hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl](2-methoxy-6-methylphenyl)methanone | C15H20O5 | 详情 | 详情 | |
| (V) | 11213 | [(4R,5S)-5-[(Methoxymethoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl](2-methoxy-6-methylphenyl)methanone | C17H24O6 | 详情 | 详情 | |
| (VI) | 11214 | benzyl (2R,3R,5S)-5-[(benzyloxy)methyl]-2-formyl-3-[(methoxymethoxy)methyl]tetrahydro-1H-pyrrole-1-carboxylate | C24H29NO6 | 详情 | 详情 | |
| (VII) | 11215 | benzyl (2R,3R,5S)-5-[(benzyloxy)methyl]-2-[2-[3-methoxy-2-([(4R,5S)-5-[(methoxymethoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]carbonyl)phenyl]acetyl]-3-[(methoxymethoxy)methyl]-1-pyrrolidinecarboxylate | C41H51NO12 | 详情 | 详情 | |
| (VIII) | 11216 | benzyl (2R,3R,5S)-5-[(benzyloxy)methyl]-2-(8-methoxy-1-[(4S,5S)-5-[(methoxymethoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-3-isoquinolinyl)-3-[(methoxymethoxy)methyl]-1-pyrrolidinecarboxylate | C41H50N2O10 | 详情 | 详情 | |
| (IX) | 11217 | benzyl (2R,3R,5S)-5-[(benzyloxy)methyl]-2-((1R,3S)-8-methoxy-1-[(4S,5S)-5-[(methoxymethoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2,3,4-tetrahydro-3-isoquinolinyl)-3-[(methoxymethoxy)methyl]-1-pyrrolidinecarboxylate | C41H54N2O10 | 详情 | 详情 | |
| (X) | 11218 | 2,2,2-trichloroethyl (1R,3S)-3-[(2R,3R,5S)-1-[(benzyloxy)carbonyl]-5-[(benzyloxy)methyl]-3-[(methoxymethoxy)methyl]pyrrolidinyl]-8-methoxy-1-[(4S,5S)-5-[(methoxymethoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate | C44H55Cl3N2O12 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)The trichloroethyl ester (X) is treated with concentrated HCl in methanol to eliminate the isopropylidene group, affording the diol (XI). The oxidation of (XI) with sodium periodate, followed by reduction of the resulting aldehyde, gives the primary alcohol (XII). Acetylation of (XII) with acetic anhydride, followed by debenzylation with hydrogen over Pd/C and oxidation with oxalyl chloride, gives the aldehyde (XIII), which is cyclized by treatment with Zn and acetic acid to the tetracyclic alcohol (XIV). The reaction of (XIV) with trimethylsilyl cyanide and ZnCl2 in dichloromethane gives the nitrile (XV), which is treated with trifluoroacetic acid to eliminate the benzyl and the methoxymethyl groups, yielding the primary alcohol (XVI). The methylation of the NH group of (XVI) with formaldehyde and sodium cyanoborohydride in methanol affords the N-methyl derivative (XVII), which is oxidized with CrO3-H2SO4 to the carboxylic acid (XVIII). Elimination of the acetyl group of (XVIII) with NaOH in methanol gives the primary alcohol (XIX), which is finally cyclized by means of AgNO3 in methanol.
| 【1】 Katoh, T.; Minami, J.; Kirihara, M.; Kobayashi, Y.; Arai, K.; Nagata, Y.; Terashima, S.; Total synthesis of (-)-quinocarcin and (-)-10-decarboxyquinocarcin. Tetrahedron Lett 1993, 34, 36, 5747. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 11218 | 2,2,2-trichloroethyl (1R,3S)-3-[(2R,3R,5S)-1-[(benzyloxy)carbonyl]-5-[(benzyloxy)methyl]-3-[(methoxymethoxy)methyl]pyrrolidinyl]-8-methoxy-1-[(4S,5S)-5-[(methoxymethoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-3,4-dihydro-2(1H)-isoquinolinecarboxylate | C44H55Cl3N2O12 | 详情 | 详情 | |
| (XI) | 11219 | 2,2,2-trichloroethyl (1R,3S)-3-[(2R,3R,5S)-1-[(benzyloxy)carbonyl]-5-[(benzyloxy)methyl]-3-[(methoxymethoxy)methyl]pyrrolidinyl]-1-[(1S,2S)-1,2-dihydroxy-3-(methoxymethoxy)propyl]-8-methoxy-3,4-dihydro-2(1H)-isoquinolinecarboxylate | C41H51Cl3N2O12 | 详情 | 详情 | |
| (XII) | 11220 | 2,2,2-trichloroethyl (1R,3S)-3-[(2R,3R,5S)-1-[(benzyloxy)carbonyl]-5-[(benzyloxy)methyl]-3-[(methoxymethoxy)methyl]pyrrolidinyl]-1-(hydroxymethyl)-8-methoxy-3,4-dihydro-2(1H)-isoquinolinecarboxylate | C37H43Cl3N2O9 | 详情 | 详情 | |
| (XIII) | 11221 | 2,2,2-trichloroethyl (1R,3S)-1-[(acetoxy)methyl]-3-[(2R,3R,5S)-1-[(benzyloxy)carbonyl]-5-formyl-3-[(methoxymethoxy)methyl]pyrrolidinyl]-8-methoxy-3,4-dihydro-2(1H)-isoquinolinecarboxylate | C32H37Cl3N2O10 | 详情 | 详情 | |
| (XIV) | 11222 | benzyl (1S,2S,10R,12S,13S,15R)-10-[(acetoxy)methyl]-12-hydroxy-8-methoxy-15-[(methoxymethoxy)methyl]-11,16-diazatetracyclo[11.2.1.0(2,11).0(4,9)]hexadeca-4,6,8-triene-16-carboxylate | C29H36N2O8 | 详情 | 详情 | |
| (XV) | 11223 | benzyl (1S,2S,10R,12R,13S,15R)-10-[(acetoxy)methyl]-12-cyano-8-methoxy-15-[(methoxymethoxy)methyl]-11,16-diazatetracyclo[11.2.1.0(2,11).0(4,9)]hexadeca-4,6,8-triene-16-carboxylate | C30H35N3O7 | 详情 | 详情 | |
| (XVI) | 11224 | [(1S,2S,10R,12R,13S,15R)-12-cyano-15-(hydroxymethyl)-8-methoxy-11,16-diazatetracyclo[11.2.1.0(2,11).0(4,9)]hexadeca-4,6,8-trien-10-yl]methyl acetate | C20H25N3O4 | 详情 | 详情 | |
| (XVII) | 11225 | [(1S,2S,10R,12R,13S,15R)-12-cyano-15-(hydroxymethyl)-8-methoxy-16-methyl-11,16-diazatetracyclo[11.2.1.0(2,11).0(4,9)]hexadeca-4,6,8-trien-10-yl]methyl acetate | C21H27N3O4 | 详情 | 详情 | |
| (XVIII) | 11226 | (1S,2S,10R,12R,13S,15R)-10-[(Acetoxy)methyl]-12-cyano-8-methoxy-16-methyl-11,16-diazatetracyclo[11.2.1.0(2,11).0(4,9)]hexadeca-4,6,8-triene-15-carboxylic acid | C21H25N3O5 | 详情 | 详情 | |
| (XIX) | 11227 | (1S,2S,10R,12R,13S,15R)-12-Cyano-10-(hydroxymethyl)-8-methoxy-16-methyl-11,16-diazatetracyclo[11.2.1.0(2,11).0(4,9)]hexadeca-4,6,8-triene-15-carboxylic acid | C19H23N3O4 | 详情 | 详情 |