【结 构 式】 |
【分子编号】57276 【品名】(4aR,6S,8aS)-7-methylene-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-6-yl methyl ether; (4aR,6S,8aS)-6-methoxy-7-methylene-2-phenylhexahydropyrano[3,2-d][1,3]dioxine 【CA登记号】 |
【 分 子 式 】C15H18O4 【 分 子 量 】262.30552 【元素组成】C 68.69% H 6.92% O 24.4% |
合成路线1
该中间体在本合成路线中的序号:(I)Synthesis of the intermediate chiral tetrahydropyran-carboxylic acid methyl ester (VII): The selective reduction of the exocyclic double bond of the glycoside (I) with H2 over Pd/C in ethanol gives a mixture of the equatorial epimer (II) along with some axial compound that is eliminated by crystallization. The cleavage of the benzylidene protecting group of (II) with H2, over Pd/C in EtOH, followed by selective monoesterification of the primary OH group with PPh3, DIAD and benzoic acid yields the benzoate ester (III). The protection of (III) with Tbdms-Cl and imidazole affords the silyl ether (IV), which is debenzoylated by means of DIBAL in dichloromethane to afford the hydroxymethyl compound (V). The oxidation of (V) by means of RuCl3 and NaIO4 pin acetonitrile/CCl4 provides the chiral carboxylic acid (VI), which is finally esterified with CH3-I and K2CO3 in DMF to furnish the desired tetrahydropyran-carboxylic acid methyl ester (VII).
【1】 Smith, A.B. III; Hale, K.J.; An enantioselective synthesis of the C(10) to C(23) backbone of the potent immunosuppressant FK506. Tetrahedron Lett 1989, 30, 9, 1037. |
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) | 57276 | (4aR,6S,8aS)-7-methylene-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-6-yl methyl ether; (4aR,6S,8aS)-6-methoxy-7-methylene-2-phenylhexahydropyrano[3,2-d][1,3]dioxine | C15H18O4 | 详情 | 详情 | |
(II) | 57277 | (4aR,6S,7R,8aS)-6-methoxy-7-methyl-2-phenylhexahydropyrano[3,2-d][1,3]dioxine; (4aR,6S,7R,8aS)-7-methyl-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-6-yl methyl ether | C15H20O4 | 详情 | 详情 | |
(III) | 57278 | [(2R,3S,5R,6S)-3-hydroxy-6-methoxy-5-methyltetrahydro-2H-pyran-2-yl]methyl benzoate | C15H20O5 | 详情 | 详情 | |
(IV) | 57279 | ((2R,3S,5R,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-5-methyltetrahydro-2H-pyran-2-yl)methyl benzoate | C21H34O5Si | 详情 | 详情 | |
(V) | 57280 | ((2R,3S,5R,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-5-methyltetrahydro-2H-pyran-2-yl)methanol | C14H30O4Si | 详情 | 详情 | |
(VI) | 57281 | (2S,3S,5R,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylic acid | C14H28O5Si | 详情 | 详情 | |
(VII) | 57282 | methyl (2S,3S,5R,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylate | C15H30O5Si | 详情 | 详情 |