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【结 构 式】 
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【分子编号】54598 【品名】tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenyl(methyl)carbamate 【CA登记号】 |
【 分 子 式 】C16H31NO3 【 分 子 量 】285.42708 【元素组成】C 67.33% H 10.95% N 4.91% O 16.82% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of N-Boc-L-isoleucine (I) with O-methylhydroxylamine (II) by means of PyBOP gives the corresponding amide (III), which is condensed with allylmagnesium bromide (IV) to afford the octenone (V). The reduction of (V) with NaBH4 yields the carbinol (VI), which is N- and O-methylated with Me-I and NaH to provide the dimethylated compound (VII). Finally, the terminal double bond of (VII) is oxidated by means of NaIO4 and RuO2 to furnish the desired intermediate, the amino acid (VIII).
| 【1】 Roux, F.; et al.; Synthesis of dolastatin-10 and [R-Doe]-dolastatin-10. Tetrahedron 1994, 50, 18, 5345. |
| 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) | 30009 | (2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentanoic acid | 13139-16-7 | C11H21NO4 | 详情 | 详情 |
| (II) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
| (III) | 38788 | tert-butyl (1S,2S)-1-[[methoxy(methyl)amino]carbonyl]-2-methylbutylcarbamate | 3350-19-4 | C13H26N2O4 | 详情 | 详情 |
| (IV) | 10386 | Allyl(bromo)magnesium | 1730-25-2 | C3H5BrMg | 详情 | 详情 |
| (V) | 54596 | tert-butyl (1S)-1-(sec-butyl)-2-oxo-4-pentenylcarbamate | C14H25NO3 | 详情 | 详情 | |
| (VI) | 54597 | tert-butyl (1S,2R)-1-(sec-butyl)-2-hydroxy-4-pentenylcarbamate | C14H27NO3 | 详情 | 详情 | |
| (VII) | 54598 | tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenyl(methyl)carbamate | C16H31NO3 | 详情 | 详情 | |
| (VIII) | 54599 | (3R,4S)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-methoxy-5-methylheptanoic acid | C15H29NO5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)The reaction of the chiral oxazolidinone (I) with (Boc)2O gives the N-protected oxazolidinone (II), which is irradiated with UV light in acetonitrile in the presence of Bu3Sn-SnBu3 and the allylstannane (III) to yield the chiral 5-allyloxazolidinone (IV). Ring cleavage of (IV) by means of Cs2CO3 in methanol affords the N-protected aminoalcohol (V), which is treated with Ms-Cl and TEA in dichloromethane to provide the mesylate (VI). Epimerization of the O-Ms group of (VI) by means of Cs-OAc and 18-crown-6 in refluxing benzene gives the epimeric acetate (VII), which is hydrolyzed with K2CO3 in methanol to yield the N-protected aminoalcohol (VIII). The O-methylation of (VIII) by means of Me-I and Tl-OEt in THF affords the methyl ether (IX), which is N-methylated by means of Me-I and NaH in THF to provide the N-methyl carbamate (X). Finally, the terminal double bond of (X) is oxidated with RuCl3 and NaIO4 in CCl4/acetonitrile/water to furnish the target intermediate, the carboxylic acid (XI) (see scheme no. 149507a, intermediate (VIII)).
| 【1】 Kano, S.; et al.; Highly diastereoselective synthesis of N-Boc dolaisoleuine, unusual amino acid in dolastatin 10. Heterocycles 1990, 31, 9, 1597. |
| 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) | 54637 | (4S)-4-(sec-butyl)-5-(phenylsulfanyl)-1,3-oxazolidin-2-one | C13H17NO2S | 详情 | 详情 | |
| (II) | 54638 | tert-butyl (4S)-4-(sec-butyl)-2-oxo-5-(phenylsulfanyl)-1,3-oxazolidine-3-carboxylate | C18H25NO4S | 详情 | 详情 | |
| (III) | 40599 | Allyltributyltin; Tributyl-2-propenylstannane | 24850-33-7 | C15H32Sn | 详情 | 详情 |
| (IV) | 54639 | tert-butyl (4S,5S)-5-allyl-4-(sec-butyl)-2-oxo-1,3-oxazolidine-3-carboxylate | C15H25NO4 | 详情 | 详情 | |
| (V) | 54640 | tert-butyl (1S,2S)-1-(sec-butyl)-2-hydroxy-4-pentenylcarbamate | C14H27NO3 | 详情 | 详情 | |
| (VI) | 54641 | (1S)-1-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-methylbutyl}-3-butenyl methanesulfonate | C15H29NO5S | 详情 | 详情 | |
| (VII) | 54642 | (1R)-1-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-methylbutyl}-3-butenyl acetate | C16H29NO4 | 详情 | 详情 | |
| (VIII) | 54597 | tert-butyl (1S,2R)-1-(sec-butyl)-2-hydroxy-4-pentenylcarbamate | C14H27NO3 | 详情 | 详情 | |
| (IX) | 54643 | tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenylcarbamate | C15H29NO3 | 详情 | 详情 | |
| (X) | 54598 | tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenyl(methyl)carbamate | C16H31NO3 | 详情 | 详情 | |
| (XI) | 54599 | (3R,4S)-4-[(tert-butoxycarbonyl)(methyl)amino]-3-methoxy-5-methylheptanoic acid | C15H29NO5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)Tetrahydropyran intermediate (X). The asymmetric addition of Ipc2B-crotyl to 4-(Tbdps-O)-2-butenal (I) gives the chiral secondary alcohol (II), which is protected with benzyl bromide and NaH to yield the benzyl ether (III). The desilylation of (III) by means of TBAF affords the primary alcohol (IV), which is submitted to a Sharpless asymmetric epoxidation to provide the epoxide (V). Ring opening of (V) by means of Ti(iPrO)4 and benzoic acid gives the benzoate ester (VI), which is cyclized by means of Hg(OAc)2 to yield the tetrahydropyran derivative (VII). Hydrolysis of the benzoate group of (VII) by means of MeONa affords the trihydroxy compound (VIII), which is treated with acetone and Ts-OH to provide the acetonide (IX). Finally, oxidation of the hydroxymethyl group of (IX) by means of Swern oxidant yields the target tetrahydropyran-2-carbaldehyde intermediate (X).
| 【1】 Smith, A.B. III; Zhuang, L.; Brook, C.S.; Boldi, A.M.; McBriar, M.D.; Moser, W.H.; Murase, N.; Nakayama, K.; Verhoest, P.R.; Lin, Q.; Spongistatin synthetic studies. 1. Construction of a C(29-48) subtarget. Tetrahedron Lett 1997, 38, 50, 8667. |
| 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) | 60351 | 4-{[(1,1-dimethylethyl)(diphenyl)silyl]oxy}-2-butenal | C20H24O2Si | 详情 | 详情 | |
| (II) | 64595 | (3S,4R,5E)-7-{[tert-butyl(diphenyl)silyl]oxy}-3-methyl-1,5-heptadien-4-ol | C24H32O2Si | 详情 | 详情 | |
| (III) | 64596 | benzyl (1R,2E)-4-{[tert-butyl(diphenyl)silyl]oxy}-1-[(1S)-1-methyl-2-propenyl]-2-butenyl ether; {[(2E,4R,5S)-4-(benzyloxy)-5-methyl-2,6-heptadienyl]oxy}(tert-butyl)diphenylsilane | C31H38O2Si | 详情 | 详情 | |
| (IV) | 64597 | (2E,4R,5S)-4-(benzyloxy)-5-methyl-2,6-heptadien-1-ol | C15H20O2 | 详情 | 详情 | |
| (V) | 54598 | tert-butyl (1S,2R)-1-(sec-butyl)-2-methoxy-4-pentenyl(methyl)carbamate | C16H31NO3 | 详情 | 详情 | |
| (VI) | 64599 | (1R,2R,3S)-2-(benzyloxy)-1-[(1R)-1,2-dihydroxyethyl]-3-methyl-4-pentenyl benzoate | C22H26O5 | 详情 | 详情 | |
| (VII) | 64600 | (2R,3S,4R,5R)-2-[(acetyloxy)methyl]-4-(benzyloxy)-6-(hydroxymethyl)-5-methyltetrahydro-2H-pyran-3-yl benzoate | C24H28O7 | 详情 | 详情 | |
| (VIII) | 64601 | (2R,3S,4R,5R)-4-(benzyloxy)-2,6-bis(hydroxymethyl)-5-methyltetrahydro-2H-pyran-3-ol | C15H22O5 | 详情 | 详情 | |
| (IX) | 64602 | [(4aR,7R,8R,8aS)-8-(benzyloxy)-2,2,7-trimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]methanol | C18H26O5 | 详情 | 详情 | |
| (X) | 64603 | (4aR,7R,8R,8aS)-8-(benzyloxy)-2,2,7-trimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carbaldehyde | C18H24O5 | 详情 | 详情 |