(3R,4S,5R)-5-[(benzyloxy)methyl]-4-hydroxy-3-methyl-5-vinyl-2-pyrrolidinone -Drug Synthesis Database

【结构式】

【分子编号】43635

【品名】(3R,4S,5R)-5-[(benzyloxy)methyl]-4-hydroxy-3-methyl-5-vinyl-2-pyrrolidinone

【CA登记号】

【分子式】C₁₅H₁₉NO₃

【分子量】261.3208

【元素组成】C 68.94% H 7.33% N 5.36% O 18.37%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(L)

Treatment of allofuranose derivative (XXXIX) with Bu2SnO in toluene followed by treatment with benzyl bromide and CsF provides (XL), which is then oxidized with Jones reagent to afford ketone (XLI). Wittig reaction of (XLI) with (ethoxycarbonymethylene)triphenylphosphorane (XLII) in toluene yields olefin (XLIII), which is then reduced by means of DIBAL to give (XLIV). Alcohol (XLIV) is then converted into trichloroacetimidate (XLV) by treatment with NaH and trichloroacetonitrile (CCl3CN) in Et2O. Rearrangement of (XLV) by heating with toluene affords derivative (XLVI), which is hydrolyzed by means of TFA/H2O to yield a mixture of diols that are chromatographically separated, providing (XLVII). Oxidation of (XLVII) in MeOH by means of NaIO4 provides hemiaminal derivative (XLVIII), which is further oxidized with Jones reagent to afford lactam (IL). Removal of protecting (N-trichloroacetyl and O-formyl) groups by treatment of (IL) with NaBH4 in MeOH gives partially deprotected derivative (L).

参考文献中间体

合成目标

【1】 Chida, N.; et al.; Stereoselective total synthesis of (+)-lactacystin from D-glucose. Tetrahedron 1997, 53, 48, 16287.
【2】 Corey, E.J.; Li, W.-D.Z.; Total synthesis and biological activity of lactacystin, omuralide and analogs. Chem Pharm Bull 1999, 47, 1, 1.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XLIIIa)	43623	ethyl (E)-3-[(3aR,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-4-(benzyloxy)-2-butenoate		C₂₁H₂₈O₆	详情	详情
(XLIIIb)	43624	ethyl (Z)-3-[(3aR,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-4-(benzyloxy)-2-butenoate		C₂₁H₂₈O₆	详情	详情
(XLIVa)	43625	(Z)-3-[(3aR,5S,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-4-(benzyloxy)-2-buten-1-ol		C₁₉H₂₆O₅	详情	详情
(XLIVb)	43626	(E)-3-[(3aR,5S,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-4-(benzyloxy)-2-buten-1-ol		C₁₉H₂₆O₅	详情	详情
(XLVa)	43627	(Z)-3-[(3aR,5S,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-4-(benzyloxy)-2-butenyl 2,2,2-trichloroethanimidoate		C₂₁H₂₆Cl₃NO₅	详情	详情
(XLVb)	43628	(E)-3-[(3aR,5S,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-4-(benzyloxy)-2-butenyl 2,2,2-trichloroethanimidoate		C₂₁H₂₆Cl₃NO₅	详情	详情
(XLVIa)	43629	N-[(1R)-1-[(3aR,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-1-[(benzyloxy)methyl]-2-propenyl]-2,2,2-trichloroacetamide		C₂₁H₂₆Cl₃NO₅	详情	详情
(XLVIb)	43630	N-[(1S)-1-[(3aR,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-1-[(benzyloxy)methyl]-2-propenyl]-2,2,2-trichloroacetamide		C₂₁H₂₆Cl₃NO₅	详情	详情
(XLVIIIa)	43632	(2R,3S,4R,5R)-2-[(benzyloxy)methyl]-5-hydroxy-4-methyl-1-(2,2,2-trichloroacetyl)-2-vinylpyrrolidinyl formate		C₁₈H₂₀Cl₃NO₅	详情	详情
(XLVIIIb)	43633	(2R,3S,4R,5S)-2-[(benzyloxy)methyl]-5-hydroxy-4-methyl-1-(2,2,2-trichloroacetyl)-2-vinylpyrrolidinyl formate		C₁₈H₂₀Cl₃NO₅	详情	详情
(IL)	43634	(2R,3S,4R)-2-[(benzyloxy)methyl]-4-methyl-5-oxo-1-(2,2,2-trichloroacetyl)-2-vinylpyrrolidinyl formate		C₁₈H₁₈Cl₃NO₅	详情	详情
(XXXIX)	43620	(1R)-1-[(3aR,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-1,2-ethanediol		C₁₀H₁₈O₅	详情	详情
(XL)	43621	(1R)-1-[(3aR,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-(benzyloxy)-1-ethanol		C₁₇H₂₄O₅	详情	详情
(XLI)	43622	1-[(3aR,6R,6aR)-2,2,6-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-(benzyloxy)-1-ethanone		C₁₇H₂₂O₅	详情	详情
(XLII)	14182	ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane	1099-45-2	C₂₂H₂₁O₂P	详情	详情
(XLVII)	43631	N-[(1R)-1-[(benzyloxy)methyl]-1-[(3S,4R,5S)-4,5-dihydroxy-3-methyltetrahydro-2-furanyl]-2-propenyl]-2,2,2-trichloroacetamide		C₁₈H₂₂Cl₃NO₅	详情	详情
(L)	43635	(3R,4S,5R)-5-[(benzyloxy)methyl]-4-hydroxy-3-methyl-5-vinyl-2-pyrrolidinone		C₁₅H₁₉NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(L)

Silylation of (L) by treatment with TBSOTf and 2,6-lutidine in CH2Cl2 furnishes (LI), whose benzyl group is removed by means of Na/NH3 in THF to yield (LII). Moffat oxidation of (LII) gives aldehyde (LIII), which is treated with isopropylmagnesium bromide (LIV) in THF to afford a mixture of adducts from which (LV) is chromatographically separated. Treatment of (LV) with TFA/H2O provides (LVI), which is then treated with O3 (DMS workup) and finally oxidized with HOSO2NH2, NaH2PO4 and NaClO2 to yield carboxylic acid (X).

参考文献中间体

合成目标

【1】 Chida, N.; et al.; Stereoselective total synthesis of (+)-lactacystin from D-glucose. Tetrahedron 1997, 53, 48, 16287.
【2】 Corey, E.J.; Li, W.-D.Z.; Total synthesis and biological activity of lactacystin, omuralide and analogs. Chem Pharm Bull 1999, 47, 1, 1.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	43590	(2R,3S,4R)-3-hydroxy-2-[(1S)-1-hydroxy-2-methylpropyl]-4-methyl-5-oxo-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₅	详情	详情
(L)	43635	(3R,4S,5R)-5-[(benzyloxy)methyl]-4-hydroxy-3-methyl-5-vinyl-2-pyrrolidinone		C₁₅H₁₉NO₃	详情	详情
(LI)	43636	(3R,4S,5R)-5-[(benzyloxy)methyl]-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-5-vinyl-2-pyrrolidinone		C₂₁H₃₃NO₃Si	详情	详情
(LII)	43637	(3R,4S,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-5-(hydroxymethyl)-3-methyl-5-vinyl-2-pyrrolidinone		C₁₄H₂₇NO₃Si	详情	详情
(LIII)	43638	(2S,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-oxo-2-vinyl-2-pyrrolidinecarbaldehyde		C₁₄H₂₅NO₃Si	详情	详情
(LIV)	33398	bromo(isopropyl)magnesium	920-39-8	C₃H₇BrMg	详情	详情
(LV)	43639	(3R,4S,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-5-[(1S)-1-hydroxy-2-methylpropyl]-3-methyl-5-vinyl-2-pyrrolidinone		C₁₇H₃₃NO₃Si	详情	详情
(LVI)	43640	(3R,4S,5R)-4-hydroxy-5-[(1S)-1-hydroxy-2-methylpropyl]-3-methyl-5-vinyl-2-pyrrolidinone		C₁₁H₁₉NO₃	详情	详情

Extended Information