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【结 构 式】

【分子编号】28047

【品名】(1R,4aS,10aR)-8-hydroxy-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydro-1-phenanthrenecarboxylic acid

【CA登记号】

【 分 子 式 】C20H28O3

【 分 子 量 】316.44052

【元素组成】C 75.91% H 8.92% O 15.17%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(I)

Total syntheses of both racemic triptolide and the levo-stereoisomer have been reported. L-dehydroabietic acid is used as the starting material. The phenol derivative of this acid (I) is converted to the trifluoroacetate (II). The latter is transformed into the isocyanate (III) by means of Curtius degradation by treating with thionyl chloride and sodium azide successively, followed by heating in toluene. The tertiary amine (IV) is formed on treatment of the isocyanate with lithium aluminum hydride in in refluxing tetrahydrofuran, and then with formic acid - formaldehyde The amine is oxidized with m-chloro perhenzoic acid, and the corresponding N-oxide is formed. Cope elimination of the N-oxide gives the olefin compound (V). Treatment of the latter with osmium tetroxide and sodium periodate affords the ketone (VI). The enolate of the compound (VI), on being generated by lithium diisopropylamide is transformed into the beta-hydroxy compound (VII) with formaldehyde. After the alcohol function has been blocked, the product is treated successively with benzyloxymethyllithium and hydrochloric acid in tetrahydrofuran and the triol monobenzyl ether (VIII) is formed. The primary alcoholic group is oxidized to the aldehyde by chromic anhydride in pyridine, and the phenol is acetylated with acetic anhydride in pyridine, and compound (IX) is afforded. Dehydration of this compound gives the unsaturated aldehyde (X). On oxidation of the aldehyde to the carboxylic acid, and then hydrogenolysis of the benzyloxy group, lactonization (XI) occurs spontaneously. A carbonyl group (XII) is introduced by oxidation with chromic anhydride in acetic acid. The acetyl group of compound (XII) is removed by saponification and the carbonyl function is reduced with sodium borohydride, and the diol (XIII) results. Treatment of the diol with sodium periodate gives the epoxy dienone (XIV). The latter is transformed into the bisoxide (XV) on treatment with hydrogen peroxide. L-Triptonide (XVI) is afforded on further oxidation with 3,5-dinitroperbenzoic acid. Reduction of triptonide with sodium borohydride gives 1-triptolide.

1 Chi, Y.S.; Kim, H.P.; Kang, S.S.; Chang, H.W.; Son, K.H.; Jong, H.G.; Koxue Tongbao 1977, 22, 10, 458-460.
2 Liedtke, L.A.; Jernigan, D.; Strausbaugh, L.J.; J Am Chem Soc 1981, 2, 2, 121-131.
3 Younes, B.; Lee, Y.-P.; Bajracharya, H.; Luchi, M.; Horvat, R.; J Am Chem Soc 1980, 102, 3, 1200-1201.
4 Pagnano, P.J.; Gibson, J.K.; Cailey, C.F.; Buchanan, L.V.; J Am Chem Soc 1980, 102, 16, 5424-5425.
5 Ruyun, J.; Triptolide. Drugs Fut 1985, 10, 7, 575.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 28062 3,5-dinitrobenzenecarboperoxoic acid C7H4N2O7 详情 详情
(I) 28047 (1R,4aS,10aR)-8-hydroxy-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydro-1-phenanthrenecarboxylic acid C20H28O3 详情 详情
(II) 28048 (1R,4aS,10aR)-7-isopropyl-1,4a-dimethyl-8-[(2,2,2-trifluoroacetyl)oxy]-1,2,3,4,4a,9,10,10a-octahydro-1-phenanthrenecarboxylic acid C22H27F3O4 详情 详情
(III) 28049 (4bS,8R,8aR)-8-isocyanato-2-isopropyl-4b,8-dimethyl-4b,5,6,7,8,8a,9,10-octahydro-1-phenanthrenyl 2,2,2-trifluoroacetate C22H26F3NO3 详情 详情
(IV) 28050 (4bS,8R,8aR)-8-(dimethylamino)-2-isopropyl-4b,8-dimethyl-4b,5,6,7,8,8a,9,10-octahydro-1-phenanthrenol C21H33NO 详情 详情
(V) 28051 (4bS,8aS)-2-isopropyl-4b-methyl-8-methylene-4b,5,6,7,8,8a,9,10-octahydro-1-phenanthrenol C19H26O 详情 详情
(VI) 28052 (4aS,10aR)-8-hydroxy-7-isopropyl-4a-methyl-3,4,4a,9,10,10a-hexahydro-1(2H)-phenanthrenone C18H24O2 详情 详情
(VII) 28053 (1R,2S,4aS,10aR)-1,2-bis(hydroxymethyl)-7-isopropyl-4a-methyl-1,2,3,4,4a,9,10,10a-octahydro-1,8-phenanthrenediol C20H30O4 详情 详情
(VIII) 28054 (1R,2S,4aS,10aR)-1-[(benzyloxy)methyl]-2-(hydroxymethyl)-7-isopropyl-4a-methyl-1,2,3,4,4a,9,10,10a-octahydro-1,8-phenanthrenediol C27H36O4 详情 详情
(IX) 28055 (4bS,7S,8R,8aR)-8-[(benzyloxy)methyl]-8-hydroxy-7-(hydroxymethyl)-2-isopropyl-4b-methyl-4b,5,6,7,8,8a,9,10-octahydro-1-phenanthrenyl acetate C29H38O5 详情 详情
(X) 28056 (4bS,8aR)-8-[(benzyloxy)methyl]-7-(hydroxymethyl)-2-isopropyl-4b-methyl-4b,5,6,8a,9,10-hexahydro-1-phenanthrenyl acetate C29H36O4 详情 详情
(XI) 28057 (3bR,9bS)-7-isopropyl-9b-methyl-1-oxo-1,3,3b,4,5,9b,10,11-octahydrophenanthro[1,2-c]furan-6-yl acetate C22H26O4 详情 详情
(XII) 28058 (3bR,9bS)-7-isopropyl-9b-methyl-1,5-dioxo-1,3,3b,4,5,9b,10,11-octahydrophenanthro[1,2-c]furan-6-yl acetate C22H24O5 详情 详情
(XIII) 28059 (3bR,5S,9bS)-5,6-dihydroxy-7-isopropyl-9b-methyl-3b,4,5,9b,10,11-hexahydrophenanthro[1,2-c]furan-1(3H)-one C20H24O4 详情 详情
(XIV) 28060 (5aS,9aR,10aS,11aR)-8-isopropyl-5a-methyl-4,5,5a,10a,11,11a-hexahydro-1H-oxireno[2',3':8a,9]phenanthro[1,2-c]furan-3,9-dione C20H22O4 详情 详情
(XV) 28061 (1aS,2aR,3aS,4aR,9aS,10aS)-1a-isopropyl-9a-methyl-1a,4,4a,5,8,9,9a,10a-octahydro-2H-dioxireno[2',3':6,7:2',3':8a,9]phenanthro[1,2-c]furan-2,7(3aH)-dione C20H22O5 详情 详情
(XVI) 28063 (3bS,4aR,5aR,6aS,7aS,7bR,8aR,8bS)-6a-isopropyl-8b-methyl-3b,4,4a,7a,7b,8b,9,10-octahydrotrioxireno[2',3':6,7:2',3':8a,9:2',3':4b,5]phenanthro[1,2-c]furan-1,6(3H,6aH)-dione C20H22O6 详情 详情
Extended Information