• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】10394

【品名】Methylprednisolone

【CA登记号】83-43-2

【 分 子 式 】C22H30O5

【 分 子 量 】374.4772

【元素组成】C 70.56% H 8.07% O 21.36%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(I)

The esterification of 11beta,17alpha,21-trihydroxy-6alpha-methylpregna-1,4-diene-3,20-dione (I) with triethyl orthopropionate (II) by means of pyridinium tosylate in DMF - benzene gives the corresponding cyclic diester (III), which is partially hydrolyzed with acetic acid - sodium acetate in methanol - water, yielding the 17alpha-propionyloxy derivative (IV). Finally, this compound is acetylated with acetic anhydride and pyridine.

1 Annen, K.; Petzoldt, K.; Laurent, H.; Wiechert, R.; Hofmeister, H.; Wendt, H. (Schering AG); New 6alpha-methylprednisolone derivs. their preparation and use. EP 0072547 .
2 Naito, Y.; Sugai, S.; Kanbara, T.; Yoshida, S.; Akaboshi, S.; Ikegami, S.; Kamano, Y.; Okazaki, T:, Kajiwara, Y.; Studies on topical antiinflammatory corticosteroids. I. Syntheses and vasoconstrictive activities of 11beta,17alpha,21-trihydroxy-6alpha-methyl-1,4-pregnadiene-3,20-dione 17-ester and 17,21-diester derivatives. Chem Pharm Bull 1985, 33, 5, 1889.
3 Prous, J.; Castaner, J.; Methylprednisolone Aceponate. Drugs Fut 1993, 18, 2, 130.
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) 10394 Methylprednisolone 83-43-2 C22H30O5 详情 详情
(II) 10395 1,1,1-Triethoxypropane; 1,1-Diethoxypropyl ethyl ether; Triethyl orthopropionate 115-80-0 C9H20O3 详情 详情
(III) 10396 2'-Ethoxy-2'-ethyl-11-beta-hydroxy-6-alpha-methylspiro[gona-1,4-diene-17(R),4'-1,3-dioxane]3,5'-dione C27H38O6 详情 详情
(IV) 10397 (6S,8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11-hydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate C25H34O6 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

Methylprednisolone suleptanate with and without radiolabeling can be prepared by two different ways: 1) The reaction of suberic acid (I) with pivaloyl chloride and triethylamine followed by condensation with N-methyltaurine sodium salt (II) gives 8-oxo-8-[N-(2-sulfoethyl)-N-methylamino]octanoic acid (III), which is treated with triethylamine and HCl, affording the corresponding triethylammonium salt (IV). The condensation of (IV) with methylprednisolone (V) by means of pivaloyl chloride and dimethylaminopyridine (DMAP) in dichloromethane yields the intermediate triethylammonium salt (VI), which is finally treated with sodium hydrogen sulfate in water. 2) The reaction of 21-deoxy-21-iodomethylprednisolone (VII) with suberic acid (I) by means of diisopropylethylamine (DEA) in DMF yields the corresponding 21-hemisuberate (VIII), which is then condensed with N-methyltaurine sodium salt (II) by means of isobutyl chloroformate and triethylamine in THF.

1 Anderson, B.D.; Conradi, R.A.; Knuth, K.E.; Strategies in the design of solution-stable, water-soluble prodrugs I: A physical-organic approach to pro-moiety selection for 21-esters of corticosteroids. J Pharm Sci 1985, 74, 365-74.
2 Graul, A.; Leeson, J.; Castaner, J.; Methylprednisolone Suleptanate. Drugs Fut 1997, 22, 8, 833.
3 Anderson, B.D.; Conradi, R.A. (Pharmacia Corp.); Sulfonate containing ester prodrugs of corticosteroids. JP 1984137500; US 4472392 .
4 Pearlman, B.A. (Pharmacia Corp.); Amine salts of alkane-1,n-dicarboxylic acid mono-(2-sulfato-ethyl)amides. WO 8900558 .
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) 11820 Suberic acid; Cork acid; Octanedioic acid 505-48-6 C8H14O4 详情 详情
(II) 11821 sodium 2-(methylamino)-1-ethanesulfonate 4316-74-9 C3H8NNaO3S 详情 详情
(III) 11822 7-[N-Methyl-N-(2-sulfoethyl)carbamoyl]heptanoic acid disodium salt C11H19NNaO6S 详情 详情
(IV) 11823 N,N-diethyl-1-ethanaminium 2-[(7-carboxyheptanoyl)(methyl)amino]-1-ethanesulfonate C17H36N2O6S 详情 详情
(V) 10394 Methylprednisolone 83-43-2 C22H30O5 详情 详情
(VI) 11825 N,N-diethyl-1-ethanaminium 3-[(8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoyl)(methyl)amino]-1-propanesulfonate C40H66N2O10S 详情 详情
(VII) 11826 (6S,8S,9S,10R,11S,13S,14S,17R)-11,17-Dihydroxy-17-(2-iodoacetyl)-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one C22H29IO4 详情 详情
(VIII) 11827 sodium 8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoate C30H41NaO8 详情 详情

合成路线3

该中间体在本合成路线中的序号:(XVI)

5) The title product [3H]- or [2H]-labeled at C7 of the steroid nucleus is synthesized starting from 21-acetoxy-11beta,17alpha-dihydroxy-6-methylpregna-4,6-diene-3,20-dione (XII), which is hydrogenated with tritium or deuterium over Pd/C in methanol yielding a mixture of the two isomeric dihydro compounds (XIII) and (XIV). The treatment of this mixture with 6N HCl affords compound (XV) labeled at C7, which is dehydrogenated with SeO2 in refluxing tert-butanol and deacetylated with KOH in methanol, yielding methylprednisolone labeled with 3H or 2H at C7 (XVI). Finally, this compound is condensed with 8-oxo-8-[N-(2-sulfoethyl)-N-methylamino]octanoic acid (III) by means of tert-butoxycarbonyl chloride as before.

1 Stolle, W.T.; Runge, T.A.; Hsi, R.S.P.; Synthesis of carbon-14 and tritium labeled methylprednisolone suleptanate. J Label Compd Radiopharm 1990, 28, 255-80.
2 Graul, A.; Leeson, J.; Castaner, J.; Methylprednisolone Suleptanate. Drugs Fut 1997, 22, 8, 833.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(III) 11822 7-[N-Methyl-N-(2-sulfoethyl)carbamoyl]heptanoic acid disodium salt C11H19NNaO6S 详情 详情
(XII) 11831 2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H32O6 详情 详情
(XIII) 11832 2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XIII) 45093 2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XIII) 45094 2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XIV) 11833 2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XIV) 45095 2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XIV) 45096 2-[(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XV) 11834 2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XV) 45099 2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XV) 45100 2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate C24H34O6 详情 详情
(XVI) 10394 Methylprednisolone 83-43-2 C22H30O5 详情 详情
(XVI) 45097 (6S,8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11,17-dihydroxy-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one C22H30O5 详情 详情
(XVI) 45098 (6S,8S,9S,10R,11S,13S,14S,17R)-17-glycoloyl-11,17-dihydroxy-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one C22H30O5 详情 详情
Extended Information