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【结 构 式】 
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【药物名称】Calebin A 【化学名称】3-(4-Hydroxy-3-methoxyphenyl)-2-propenoic acid 4-(4-hydroxy-3-methoxyphenyl)-2-oxo-3-butenyl ester 【CA登记号】336784-82-8 (E-isomer) 【 分 子 式 】C21H20O7 【 分 子 量 】384.38935 |
【开发单位】University of Illinois at Chicago (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , Cognition Disorders, Treatment of, NEUROLOGIC DRUGS |
合成路线1
Vanillin (I) was protected as the tetrahydropyranyl ether (II) by treatment with dihydropyran in the presence of pyridinium p-toluenesulfonate. Similarly, hydroxyacetone (III) was converted to the corresponding tetrahydropyranyl ether (IV). Aldol condensation between aldehyde (II) and ketone (IV) using LDA in cold THF furnished the hydroxy ketone (V). Removal of the tetrahydropyranyl protecting groups of (V) under acidic conditions caused the dehydration of the beta-hydroxyl group, affording the unsaturated ketone (VI). The phenolic hydroxyl group of (VI) was then protected as the trimethylsilyl ether (VII). After protection of the phenolic hydroxyl group of ferulic acid (VIII) as the silyl ether (IX), coupling between (IX) and (VII) by means of DCC and DMAP provided the silyl-protected ester (X). This was finally desilylated by treatment with HOAc in aqueous THF.
| 【1】 Kim, D.S.H.L. (University of Illinois); Pharmaceutical compsns. useful in the prevention and treatment of beta-amyloid protein-induced disease. WO 0130335 . |
| 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) | 22701 | 4-hydroxy-3-methoxybenzaldehyde | 121-33-5 | C8H8O3 | 详情 | 详情 |
| (II) | 52071 | 3-methoxy-4-(tetrahydro-2H-pyran-2-yloxy)benzaldehyde | C13H16O4 | 详情 | 详情 | |
| (III) | 52072 | 1-hydroxyacetone | 116-09-6 | C3H6O2 | 详情 | 详情 |
| (IV) | 52073 | 1-(tetrahydro-2H-pyran-2-yloxy)acetone | C8H14O3 | 详情 | 详情 | |
| (V) | 52074 | 4-hydroxy-4-[3-methoxy-4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-1-(tetrahydro-2H-pyran-2-yloxy)-2-butanone | C21H30O7 | 详情 | 详情 | |
| (VI) | 52075 | (E)-1-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one | C11H12O4 | 详情 | 详情 | |
| (VII) | 52076 | (E)-1-hydroxy-4-[3-methoxy-4-[(trimethylsilyl)oxy]phenyl]-3-buten-2-one | C14H20O4Si | 详情 | 详情 | |
| (VIII) | 48091 | (E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid | 1135-24-6 | C10H10O4 | 详情 | 详情 |
| (IX) | 52077 | (E)-3-[3-methoxy-4-[(trimethylsilyl)oxy]phenyl]-2-propenoic acid | C13H18O4Si | 详情 | 详情 | |
| (X) | 52078 | (E)-4-[3-methoxy-4-[(trimethylsilyl)oxy]phenyl]-2-oxo-3-butenyl (E)-3-[3-methoxy-4-[(trimethylsilyl)oxy]phenyl]-2-propenoate | C27H36O7Si2 | 详情 | 详情 |
合成路线2
A more direct procedure for the preparation of the title ester has been reported, consisting in coupling unprotected acid (VIII) with keto alcohol (VI) by means of DCC in the presence of DMAP and DMAP-hydrochloride.
| 【1】 Kim, J.Y.; Kim, D.S.H.L.; Total synthesis of calebin-A, preparation of its analogues, and their neuronal cell protectivity against beta-amyloid insult. Bioorg Med Chem Lett 2001, 11, 18, 2541. |