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【结 构 式】 
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【分子编号】18044 【品名】3-Oxopregna-4,9(11)-diene-21,17-carbolactone 【CA登记号】 |
【 分 子 式 】C22H28O3 【 分 子 量 】340.46252 【元素组成】C 77.61% H 8.29% O 14.1% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)Starting from enol ether (XIV), its reaction with the sulfonium ylide from trimethylsulfonium methylsulfate and KOH in DMSO-THF at 80 C afforded epoxide (XV). This was converted to the lactone (XVI) by treatment with diethyl malonate and sodium ethoxide in refluxing ethanol, and then decarboxylated to (XVII) on heating with NaCl in moist DMF. Hydrolysis of enol ether with AcOH in boiling ethanol-water provided dienone (XVIII), which was oxidized to trienone (XIX) by means of a sequence consisting of halogenation with N-bromosuccinimide and then dehydrohalogenation with DABCO and LiBr in DMF. Using the analogous reactions as in Scheme 1, (XIX) was converted to enamine (XX), then hydrolyzed to diketone (XXI), treated with NaOMe to give dienone (XXII), and finally converted to the target epoxide.
| 【1】 Ng, J.S.; Wang, P.T.; Baez, J.A.; Liu, C.; Anderson, D.K.; Lawson, J.P.; Erb, D.; Wieczorek, J.; Mucciariello, G.; Vanzanella, F.; Kunda, S.A.; Letendre, L.J.; Pozzo, M.J.; Sing, Y.-L.L. (Pharmacia Corp.); Process for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olifinic double bonds. WO 9721720 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 18040 | (8S,10R,13S,14S)-3-methoxy-10,13-dimethyl-1,2,7,8,10,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C20H26O2 | 详情 | 详情 | |
| (XV) | 18041 | 3-Methoxyspiro[androsta-3,5,9(11)-triene-17(S),2'-oxirane] | C21H28O2 | 详情 | 详情 | |
| (XVI) | 18042 | 21-(Ethoxycarbonyl)-3-methoxypregan-3,5,9(11)-triene-21,17-carbolactone | C26H34O5 | 详情 | 详情 | |
| (XVII) | 18043 | 3-Methoxypregna-3,5,9(11)-triene-21,17-carbolactone | C23H30O3 | 详情 | 详情 | |
| (XVIII) | 18044 | 3-Oxopregna-4,9(11)-diene-21,17-carbolactone | C22H28O3 | 详情 | 详情 | |
| (XIX) | 18045 | 3-Oxopregan-4,6,9(11)-triene-21,17-carbolactone | C22H26O3 | 详情 | 详情 | |
| (XX) | 18046 | 4'-Amino-5-beta-cyano-7-alpha,4-metheno-3-oxo-17-alpha-pregn-9(11)-ene-21,17-carbolactone | C24H28N2O3 | 详情 | 详情 | |
| (XXI) | 18047 | 5-beta-Cyano-4,7-alpha-methano-3,4'-dioxo-17-alpha-pregn-9(11)-ene-21,17-carbolactone | C24H27NO4 | 详情 | 详情 | |
| (XXII) | 18034 | 7-Alpha-(methoxycarbonyl)-3-oxopregna-4,9(11)-diene-21,17-carbolactone | C24H30O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVIII)Alternatively, lactone (XVIII) obtained from enol ether (XIV) as in the Scheme 3, was epoxidized to give (XXIII), which was dehydrogenated using either DDQ or chloranil to afford dienone (XXIV). Conversion to enamine (XXV), then hydrolysis to diketone (XXVI), and ring opening with NaOMe furnished eplerenone.
| 【1】 Ng, J.S.; Wang, P.T.; Baez, J.A.; Liu, C.; Anderson, D.K.; Lawson, J.P.; Erb, D.; Wieczorek, J.; Mucciariello, G.; Vanzanella, F.; Kunda, S.A.; Letendre, L.J.; Pozzo, M.J.; Sing, Y.-L.L. (Pharmacia Corp.); Process for preparation of 7 alpha-carboxyl 9,11-epoxy steroids and intermediates useful therein and a general process for the epoxidation of olifinic double bonds. WO 9721720 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 18040 | (8S,10R,13S,14S)-3-methoxy-10,13-dimethyl-1,2,7,8,10,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C20H26O2 | 详情 | 详情 | |
| (XV) | 18041 | 3-Methoxyspiro[androsta-3,5,9(11)-triene-17(S),2'-oxirane] | C21H28O2 | 详情 | 详情 | |
| (XVI) | 18042 | 21-(Ethoxycarbonyl)-3-methoxypregan-3,5,9(11)-triene-21,17-carbolactone | C26H34O5 | 详情 | 详情 | |
| (XVII) | 18043 | 3-Methoxypregna-3,5,9(11)-triene-21,17-carbolactone | C23H30O3 | 详情 | 详情 | |
| (XVIII) | 18044 | 3-Oxopregna-4,9(11)-diene-21,17-carbolactone | C22H28O3 | 详情 | 详情 | |
| (XXIII) | 18048 | 9-alpha,11-alpha-Epoxy-3-oxopregn-4-ene-21,17-carbolactone | C22H28O4 | 详情 | 详情 | |
| (XXIV) | 18049 | 9-alpha,11-alpha-Epoxy-3-oxopregna-4,6-diene-21,17-carbolactone | C22H26O4 | 详情 | 详情 | |
| (XXV) | 18050 | 4'-Amino-5-beta-cyano-9-alpha,11-alpha-epoxy-7-alpha,4-metheno-3-oxo-17-alpha-pregnane-21,17-carbolactone | C24H28N2O4 | 详情 | 详情 | |
| (XXVI) | 18051 | 5-beta-Cyano-9-alpha,11-alpha-epoxy-4,7-alpha-methano-3,4'-dioxo-17-alpha-pregnane-21,17-carbolactone | C24H27NO5 | 详情 | 详情 |