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【结 构 式】

【分子编号】55472

【品名】(6R)-6-{(E)-2-[(4R,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolan-4-yl]ethenyl}-5,6-dihydro-2H-pyran-2-one

【CA登记号】

【 分 子 式 】C33H41BrO5Si

【 分 子 量 】625.67504

【元素组成】C 63.35% H 6.6% Br 12.77% O 12.79% Si 4.49%

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:(XXIII)

The enantioselective condensation of 3-(trimethylsilyl)propynal (V) with allylmagnesium bromide (VI) by means of (+)-Ipc2B-OMe as chiral catalyst gives hex-5-en-1-yn-3(R)-ol (VII), which is silylated with Tbdps-Cl and imidazole to yield the silyl ether (VIII). The oxidation of the terminal double bond of (VII) by means of OsO4 and NaIO4 affords the aldehyde (IX), which is submitted to a Wittig condensation with the phosphorane (X) in benzene to provide the unsaturated ester (XI). The enantioselective dihydroxylation of the double bond of (XI) with AD-mix-beta in tert-butanol/water gives the dihydroxyester (XII), which is protected with 2-methoxypropene (XIII) and PPTS to yield the isopropylidene ketal (XIV). The bromination of the triple bond of (XIV), followed by selective hydrogenation, affords the cis-bromovinyl compound (XV), whose ester group is reduced with LiAlH4 in THF to provide the primary alcohol (XVI). The oxidation of (XVI) with (COCl)2 and TEA in DMSO gives the carbaldehyde (XVII), which is submitted to a Wittig condensation with the phosphorane (XVIII) in hot dichloromethane to yield the diunsaturated aldehyde (XIX). The enantioselective condensation of aldehyde (XIX) with allylmagnesium bromide catalyzed by (+)Ipc2-B-OMe affords the chiral alcohol (XX), which is esterified with acryloyl chloride (XXI) and DIEA in dichloromethane to provide the ester (XXII). Compound (XXII) is submitted to a ring-closing metathesis catalyzed by a Rh catalyst (Grubbs's catalyst), yielding the dihydropyran derivative (XXIII), which is submitted to cleavage of the acetonide group by means of Montmorillonite K 10 to afford the diol (XXIV). The condensation of the bromovinyl group of (XXIV) with the intermediate boronic ester (IV) by means of Pd(PPh3)4 and Ag2O gives compound (XXV) with the complete backbone of the target fostriecin. The selective monosilylation of (XXV) with Tbdps-OTf gives the intermediate (XXVI).

1 Falck, J.R.; Reddy, Y.K.; Asymmetric total synthesis of (+)-fostriecin. Org Lett 2002, 4, 6, 969.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IV) 55458 tert-butyl(diphenyl){[(2E,4Z)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4-pentadienyl]oxy}silane; tert-butyl(diphenyl)silyl (2E,4Z)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,4-pentadienyl ether C27H37BO3Si 详情 详情
(V) 20043 3-(trimethylsilyl)-2-propynal C6H10OSi 详情 详情
(VI) 10386 Allyl(bromo)magnesium 1730-25-2 C3H5BrMg 详情 详情
(VII) 55459 (3R)-5-hexen-1-yn-3-ol C6H8O 详情 详情
(VIII) 55460 tert-butyl(diphenyl)silyl (1R)-1-ethynyl-3-butenyl ether; tert-butyl{[(1R)-1-ethynyl-3-butenyl]oxy}diphenylsilane C22H26OSi 详情 详情
(IX) 55461 (3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-4-pentynal C21H24O2Si 详情 详情
(X) 37071 ethyl 2-(triphenylphosphoranylidene)propanoate 5717-37-3 C23H23O2P 详情 详情
(XI) 55462 ethyl (E,5R)-5-{[tert-butyl(diphenyl)silyl]oxy}-2-methyl-2-hepten-6-ynoate C26H32O3Si 详情 详情
(XII) 55463 ethyl (2S,3R,5R)-5-{[tert-butyl(diphenyl)silyl]oxy}-2,3-dihydroxy-2-methyl-6-heptynoate C26H34O5Si 详情 详情
(XIII) 17354 isopropenyl methyl ether; 2-methoxy-1-propene 116-11-0 C4H8O 详情 详情
(XIV) 55464 ethyl (4S,5R)-5-((2R)-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butynyl)-2,2,4-trimethyl-1,3-dioxolane-4-carboxylate C29H38O5Si 详情 详情
(XV) 55465 ethyl (4S,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolane-4-carboxylate C29H39BrO5Si 详情 详情
(XVI) 55466 [(4R,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolan-4-yl]methanol C27H37BrO4Si 详情 详情
(XVII) 55467 (4S,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolane-4-carbaldehyde C27H35BrO4Si 详情 详情
(XVIII) 55468 2-(triphenylphosphoranylidene)acetaldehyde C20H17OP 详情 详情
(XIX) 55469 (E)-3-[(4R,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-propenal C29H37BrO4Si 详情 详情
(XX) 55470 (1E,3R)-1-[(4R,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolan-4-yl]-1,5-hexadien-3-ol C32H43BrO4Si 详情 详情
(XXI) 11577 Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride 814-68-6 C3H3ClO 详情 详情
(XXII) 55471 (1R)-1-{(E)-2-[(4R,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolan-4-yl]ethenyl}-3-butenyl acrylate C35H45BrO5Si 详情 详情
(XXIII) 55472 (6R)-6-{(E)-2-[(4R,5R)-5-((2R,3Z)-4-bromo-2-{[tert-butyl(diphenyl)silyl]oxy}-3-butenyl)-2,2,4-trimethyl-1,3-dioxolan-4-yl]ethenyl}-5,6-dihydro-2H-pyran-2-one C33H41BrO5Si 详情 详情
(XXIV) 55473 (6R)-6-((1E,3R,4R,6R,7Z)-8-bromo-6-{[tert-butyl(diphenyl)silyl]oxy}-3,4-dihydroxy-3-methyl-1,7-octadienyl)-5,6-dihydro-2H-pyran-2-one C30H37BrO5Si 详情 详情
(XXV) 55474 (6R)-6-((1E,3R,4R,6R,7Z,9Z,11E)-6,13-bis{[tert-butyl(diphenyl)silyl]oxy}-3,4-dihydroxy-3-methyl-1,7,9,11-tridecatetraenyl)-5,6-dihydro-2H-pyran-2-one C51H62O6Si2 详情 详情
(XXVI) 55475 (6R)-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6,13-tris{[tert-butyl(diphenyl)silyl]oxy}-4-hydroxy-3-methyl-1,7,9,11-tridecatetraenyl)-5,6-dihydro-2H-pyran-2-one C67H80O6Si3 详情 详情
Extended Information