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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 2 条

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
Extended Information