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【结 构 式】

【分子编号】10226

【品名】(1R,2S,5R)-2-(2-Hydroxy-1-methylethyl)-5-methylcyclohexanol

【CA登记号】

【 分 子 式 】C10H20O2

【 分 子 量 】172.2676

【元素组成】C 69.72% H 11.7% O 18.58%

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:(XIX)

3) The cyclization of (R)-(+)-citronellal (XVIII) with ZnBr2 followed by reaction with diborane and H2O2 gives the diol (XI), which is selectively benzylated with benzyl chloride and NaH to the monobenzyl ether (XX). The oxidation of (XX) with the Jones reagent yields the cyclohexanone (XXI), which is condensed with 3-(trimethylsilyl)-3-buten-2-one (XXII) by means of lithium diisopropylamide to the dione (XXIII). The cyclization of (XXIII) by means of Ba(OH)2 and oxalic acid affords the benzylated octahydronaphthalenone (XXIV), which by reduction with NaBH4 followed by reoxidation with the Jones reagent gives the decalinone (XXV). The Grignard methylation of (XXV) with methylmagnesium iodide yields the tertiary alcohol (XXVI), which is dehydrated with p-toluenesulfonic acid to the octahydronaphthalene (XXVII). The debenzylation of (XXVII) with sodamide, followed by oxidation with the Jones reagent and methylation with diazomethane affords the ester (XXVIII), which is ozonolyzed with O3 to the formyl ketone (XXIX). Selective protection of the ketone group with propane-1,3-dithiol (XXX) and p-toluenesulfonic acid gives the substituted 1,3-dithiane (XXXI), which is treated with methyl orthoformate and p-toluenesulfonic acid to yield the methoxymethylene derivative (XXXII). The elimination of the dithiane group with HgCl2 in aqueous acetonitrile affords the ketoester (XXXIII), which is submitted to a photochemical oxidation using rose bengal as catalyst in methanol, giving the peroxide (XXXIV). Finally, this compound is cyclized by means of HClO4 and OsO4. 4) The benzylated octahydronaphthalenone (XXIV) can also be obtained by benzylation of the ketone (VIII) with benzyl bromide by means of NaH in DMF.

1 Deshpande, V.H.; Bhonsle, J.B.; Pandey, B.; Ravindranathan, T.; New synthetic strategies towards (+)-artemisinin. Tetrahedron Lett 1994, 35, 30, 5489.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VII) 10215 (3aS,6R,6aS,10aR)-3,6-Dimethyloctahydro-2H-naphtho[8a,1-b]furan-9(10H)-one C14H22O2 详情 详情
(XVIII) 10225 (3R)-3,7-Dimethyl-6-octenal; L-Citronellal 5949-05-3 C10H18O 详情 详情
(XIX) 10226 (1R,2S,5R)-2-(2-Hydroxy-1-methylethyl)-5-methylcyclohexanol C10H20O2 详情 详情
(XX) 10227 (1R,2S,5R)-2-[2-(Benzyloxy)-1-methylethyl]-5-methylcyclohexanol C17H26O2 详情 详情
(XXI) 10228 (2S,5R)-2-[2-(Benzyloxy)-1-methylethyl]-5-methylcyclohexanone C17H24O2 详情 详情
(XXII) 10229 3-(Trimethylsilyl)-3-buten-2-one C7H14OSi 详情 详情
(XXIII) 10230 (2S,3R,6S)-6-[2-(Benzyloxy)-1-methylethyl]-3-methyl-2-(3-oxobutyl)cyclohexanone C21H30O3 详情 详情
(XXIV) 10231 (4aS,5R,8S)-8-[2-(Benzyloxy)-1-methylethyl]-5-methyl-4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone C21H28O2 详情 详情
(XXV) 10232 (4aS,5R,8R,8aS)-8-[2-(Benzyloxy)-1-methylethyl]-5-methyloctahydro-2(1H)-naphthalenone C21H30O2 详情 详情
(XXVI) 10233 (4aS,5R,8R,8aS)-8-[2-(Benzyloxy)-1-methylethyl]-2,5-dimethyldecahydro-2-naphthalenol C22H34O2 详情 详情
(XXVII) 10234 2-[(1R,4R,4aS,8aS)-4,7-Dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propyl benzyl ether; (1R,4R,4aS,8aS)-1-[2-(Benzyloxy)-1-methylethyl]-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene C22H32O 详情 详情
(XXVIII) 10235 methyl 2-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propanoate C16H26O2 详情 详情
(XXIX) 10236 methyl 2-[(1R,2S,3S,4R)-2-formyl-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate C16H26O4 详情 详情
(XXX) 29729 1,3-propanedithiol; 3-sulfanylpropylhydrosulfide 109-80-8 C3H8S2 详情 详情
(XXXI) 10237 methyl 2-[(1R,2S,3S,4R)-2-formyl-4-methyl-3-[2-(2-methyl-1,3-dithian-2-yl)ethyl]cyclohexyl]propanoate C19H32O3S2 详情 详情
(XXXII) 10238 methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-[2-(2-methyl-1,3-dithian-2-yl)ethyl]cyclohexyl]propanoate C20H34O3S2 详情 详情
(XXXIII) 10239 methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate C17H28O4 详情 详情
(XXXIV) 10240 methyl 2-[(3R,5aS,6R,9S,9aR)-9a-(dimethoxymethyl)-3-methoxy-3,6-dimethyloctahydro-3H-1,2-benzodioxepin-9-yl]propanoate C19H34O7 详情 详情

合成路线2

该中间体在本合成路线中的序号:(II)

 

1 Deshpande VH, Bhonsle JB, Pandey B, et al. 1994. New synthesis strategies towards(+) -artemisinin. Tetrahedron Lett, 35(30):5489~5492.
2 Liu HJ, Yeh WL, Chew SY. 1993. Atotal synthesis of antimalarial natural product (+) -quinghaosu. Tetrahedron Lett, 34(28): 4435~4438
3 Xu XX, Zhu J, Huang DZ, et al. 1986. Total synthesis of arteannuin and deoxyarteannuin. Tetrahedron, 42(3): 819~828.
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) 10225 (3R)-3,7-Dimethyl-6-octenal; L-Citronellal 5949-05-3 C10H18O 详情 详情
(II) 10226 (1R,2S,5R)-2-(2-Hydroxy-1-methylethyl)-5-methylcyclohexanol C10H20O2 详情 详情
(III) 10227 (1R,2S,5R)-2-[2-(Benzyloxy)-1-methylethyl]-5-methylcyclohexanol C17H26O2 详情 详情
(IV) 10228 (2S,5R)-2-[2-(Benzyloxy)-1-methylethyl]-5-methylcyclohexanone C17H24O2 详情 详情
(V) 10230 (2S,3R,6S)-6-[2-(Benzyloxy)-1-methylethyl]-3-methyl-2-(3-oxobutyl)cyclohexanone C21H30O3 详情 详情
(VI) 10231 (4aS,5R,8S)-8-[2-(Benzyloxy)-1-methylethyl]-5-methyl-4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone C21H28O2 详情 详情
(VII) 10232 (4aS,5R,8R,8aS)-8-[2-(Benzyloxy)-1-methylethyl]-5-methyloctahydro-2(1H)-naphthalenone C21H30O2 详情 详情
(VIII) 10233 (4aS,5R,8R,8aS)-8-[2-(Benzyloxy)-1-methylethyl]-2,5-dimethyldecahydro-2-naphthalenol C22H34O2 详情 详情
(IX) 10234 2-[(1R,4R,4aS,8aS)-4,7-Dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propyl benzyl ether; (1R,4R,4aS,8aS)-1-[2-(Benzyloxy)-1-methylethyl]-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalene C22H32O 详情 详情
(X) 10235 methyl 2-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydro-1-naphthalenyl]propanoate C16H26O2 详情 详情
(XI) 10236 methyl 2-[(1R,2S,3S,4R)-2-formyl-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate C16H26O4 详情 详情
(XII) 10237 methyl 2-[(1R,2S,3S,4R)-2-formyl-4-methyl-3-[2-(2-methyl-1,3-dithian-2-yl)ethyl]cyclohexyl]propanoate C19H32O3S2 详情 详情
(XIII) 10238 methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-[2-(2-methyl-1,3-dithian-2-yl)ethyl]cyclohexyl]propanoate C20H34O3S2 详情 详情
(XIV) 10239 methyl 2-[(1S,3S,4R)-2-[(Z)-methoxymethylidene]-4-methyl-3-(3-oxobutyl)cyclohexyl]propanoate C17H28O4 详情 详情
(XV) 10240 methyl 2-[(3R,5aS,6R,9S,9aR)-9a-(dimethoxymethyl)-3-methoxy-3,6-dimethyloctahydro-3H-1,2-benzodioxepin-9-yl]propanoate C19H34O7 详情 详情
Extended Information