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【结 构 式】

【分子编号】58123

【品名】ethyl (E,4R,5S)-4,5-bis{[tert-butyl(dimethyl)silyl]oxy}-6-oxo-2-hexenoate

【CA登记号】

【 分 子 式 】C20H40O5Si2

【 分 子 量 】416.7056

【元素组成】C 57.65% H 9.68% O 19.2% Si 13.48%

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:(IX)

The monoprotection of acetonide dol (I) by means of Pmb-Cl and KOH in refluxing benzene gives the alcohol (II), which is submitted to a Swern oxidation, yielding the aldehyde (III). The Horner Wadswort Emmons condensation of (III) with phosphonate (IV) by means of NaH in THF affords the unsaturated ester (V), which is deprotected by means of HCl in hot ethanol to provide the diol (VI), which is reprotected by means of Tbdms-OTf and TEA in dichloromethane to gives the bis silyl ether (VII).The selective deprotection of (VII) by means of DDQ in aqueous acetonitrile yields the primary alcohol (VIII), which is submitted to a Swern oxidation to afford the corresponding aldehyde (IX). The cyclization of (IX) by means of PhCH2-S-Li in THF provides the chiral cyclopentanol (X), which is desilylated by means of HF in aqueous acetonitrile to give the trihydroxy compound (XI). The vicinal cis diols of (XI) are selectively protected with acetone and Ts-OH to yield the acetonide (XII), which is desulfurized by oxidation with NaIO4 and heating at 180 C in decalin to afford the cyclopentenol (XIII). The oxidation of (XIII) by means of PDC in dichloromethane provides the cyclopentenone (XIV), which is reduced at the ester and ketone groups by means of DIBAL in toluene to give the diol (XV). The selective silylation of the primary OH group of (XV) by means of Tbdms-Cl, TEA and DMAP in dichloromethane yields the primary silyl ether (XVI), which is condensed with adenine (XVII) by means of DIAD and PPH3 in THF to afford the protected adduct (XVIII). Finally this compound is deprotected by means of HCl in methanol to provide the target Neplanocin A.

1 Ono, M.; et al.; Total synthesis of (-)-neplanocin A by using lithium thiolate-initiated Michael-aldol tandem cyclization reaction. J Org Chem 2001, 66, 24, 8199.
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) 52911 [(4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol C7H14O4 详情 详情
(II) 58117 ((4R,5R)-5-{[(4-methoxybenzyl)oxy]methyl}-2,2-dimethyl-1,3-dioxolan-4-yl)methanol C15H22O5 详情 详情
(III) 58118 (4S,5R)-5-{[(4-methoxybenzyl)oxy]methyl}-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde C15H20O5 详情 详情
(IV) 10019 Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate 867-13-0 C8H17O5P 详情 详情
(V) 58119 ethyl (E)-3-((4R,5R)-5-{[(4-methoxybenzyl)oxy]methyl}-2,2-dimethyl-1,3-dioxolan-4-yl)-2-propenoate C19H26O6 详情 详情
(VI) 58120 ethyl (E,4R,5R)-4,5-dihydroxy-6-[(4-methoxybenzyl)oxy]-2-hexenoate C16H22O6 详情 详情
(VII) 58121 ethyl (E,4R,5R)-4,5-bis{[tert-butyl(dimethyl)silyl]oxy}-6-[(4-methoxybenzyl)oxy]-2-hexenoate C28H50O6Si2 详情 详情
(VIII) 58122 ethyl (E,4R,5R)-4,5-bis{[tert-butyl(dimethyl)silyl]oxy}-6-hydroxy-2-hexenoate C20H42O5Si2 详情 详情
(IX) 58123 ethyl (E,4R,5S)-4,5-bis{[tert-butyl(dimethyl)silyl]oxy}-6-oxo-2-hexenoate C20H40O5Si2 详情 详情
(X) 58124 ethyl (1S,2R,3S,4R,5R)-2-(benzylsulfanyl)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxycyclopentanecarboxylate C27H48O5SSi2 详情 详情
(XI) 58125 ethyl (1S,2R,3S,4R,5R)-2-(benzylsulfanyl)-3,4,5-trihydroxycyclopentanecarboxylate C15H20O5S 详情 详情
(XII) 58126 ethyl (3aR,4S,5R,6S,6aS)-5-(benzylsulfanyl)-6-hydroxy-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxylate C18H24O5S 详情 详情
(XIII) 58127 ethyl (3aR,6R,6aS)-6-hydroxy-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxylate C11H16O5 详情 详情
(XIV) 58128 ethyl (3aR,6aR)-2,2-dimethyl-6-oxo-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole-4-carboxylate C11H14O5 详情 详情
(XV) 58129 (3aS,4S,6aR)-6-(hydroxymethyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol C9H14O4 详情 详情
(XVI) 58130 (3aS,4S,6aR)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol C15H28O4Si 详情 详情
(XVII) 10343 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine 73-24-5 C5H5N5 详情 详情
(XVIII) 58131 9-[(3aS,4R,6aR)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9H-purin-6-ylamine; 9-[(3aS,4R,6aR)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9H-purin-6-amine C20H31N5O3Si 详情 详情
Extended Information