【结 构 式】 |
【分子编号】52913 【品名】(4S,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde 【CA登记号】 |
【 分 子 式 】C13H26O4Si 【 分 子 量 】274.43254 【元素组成】C 56.9% H 9.55% O 23.32% Si 10.23% |
合成路线1
该中间体在本合成路线中的序号:(V)The reaction of D-tartaric acid (I) with refluxing acetone and sulfuric acid gives the isopropylidene ketal (II), which is reduced with LiAlH4 to yield 2,3-O-isopropylidene-D-threitol (III). The monosilylation of (III) with Tbdms-Cl and NaH affords the monosilyl ether (IV), which is submitted to a Swern oxidation to provide the aldehyde (V). The reaction of (V) with CBr4, PPh3 and BuLi in dichloromethane gives the acetylene (VI), which is desilylated with TBAF in THF to yield the carbinol (VII). The carbinol (VII) is treated with CBr4 and PPh3 in dichloromethane to afford the bromide (VIII), which is condensed with N-benzyl-N-(trimethylsilyl)amine (IX) by means of K2CO3 in refluxing acetonitrile, providing the tertiary amine (X). The cyclization of (X) by means of ultraviolet light in isopropanol/dichloromethane gives the methylenepiperidine (XI), which is submitted to hydroboration with 9-BBN and NaOH in THF to yield the carbinol (XII) as a single diastereomer. The cleavage of the ketal group of (XII) by treatment with HCl in methanol affords the chiral 1-benzyl-5-(hydroxymethyl)piperidine-3,4-diol (XIII), which is finally debenzylated by means of H2 over Pd(OH)2 in ethanol to furnish the target isofagomine.
【1】 Feit, P.W.; 1,4-Bismethanesulfonates of the stereoisomeric butanetetraols and related compounds. J Med Chem 1964, 7, 14. |
【2】 Iida, H.; et al.; Total synthesis of (+)-nojirimycin and (+)-1-deoxynojirimycin. J Org Chem 1987, 52, 15, 3337. |
【3】 Pandey, G.; Kapur, M.; A general strategy towards the synthesis of 1-N-iminosugar type glycosidase inhibitors: Demonstration by the synthesis of D- as well as L-glucose type iminosugars (isofagomines). Tetrahedron Lett 2000, 41, 45, 8821. |
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) | 16696 | Diethyl L-(+)-Tartrate; diethyl (2S,3S)-2,3-dihydroxybutanedioate | 87-91-2 | C8H14O6 | 详情 | 详情 |
(II) | 52910 | diethyl (4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate | C11H18O6 | 详情 | 详情 | |
(III) | 52911 | [(4R,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol | C7H14O4 | 详情 | 详情 | |
(IV) | 52912 | [(4R,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol | C13H28O4Si | 详情 | 详情 | |
(V) | 52913 | (4S,5R)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde | C13H26O4Si | 详情 | 详情 | |
(VI) | 52914 | tert-butyl{[(4R,5R)-5-ethynyl-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}dimethylsilane; tert-butyl(dimethyl)silyl [(4R,5R)-5-ethynyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ether | C14H26O3Si | 详情 | 详情 | |
(VII) | 52915 | [(4R,5R)-5-ethynyl-2,2-dimethyl-1,3-dioxolan-4-yl]methanol | C8H12O3 | 详情 | 详情 | |
(VIII) | 52916 | (4S,5R)-4-(bromomethyl)-5-ethynyl-2,2-dimethyl-1,3-dioxolane | C8H11BrO2 | 详情 | 详情 | |
(IX) | 52917 | N-benzyl-N-[(trimethylsilyl)methyl]amine; phenyl-N-[(trimethylsilyl)methyl]methanamine | C11H19NSi | 详情 | 详情 | |
(X) | 52918 | N-benzyl-N-{[(4R,5R)-5-ethynyl-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-N-[(trimethylsilyl)methyl]amine; N-benzyl[(4R,5R)-5-ethynyl-2,2-dimethyl-1,3-dioxolan-4-yl]-N-[(trimethylsilyl)methyl]methanamine | C19H29NO2Si | 详情 | 详情 | |
(XI) | 52919 | (3aR,7aR)-5-benzyl-2,2-dimethyl-7-methylenehexahydro[1,3]dioxolo[4,5-c]pyridine | C16H21NO2 | 详情 | 详情 | |
(XII) | 52920 | [(3aR,7R,7aR)-5-benzyl-2,2-dimethylhexahydro[1,3]dioxolo[4,5-c]pyridin-7-yl]methanol | C16H23NO3 | 详情 | 详情 | |
(XIII) | 52921 | (3R,4R,5R)-1-benzyl-5-(hydroxymethyl)-3,4-piperidinediol | C13H19NO3 | 详情 | 详情 |