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【结 构 式】 
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【分子编号】47788 【品名】(9R,10R)-9,10-dihydroxy-5-methoxy-4,8,8-trimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one 【CA登记号】 |
【 分 子 式 】C16H18O6 【 分 子 量 】306.31532 【元素组成】C 62.74% H 5.92% O 31.34% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The peptide resin (XV) was then coupled with tert-butyl hydrogensuccinate (XVI) yielding resin (XVII). Further Dess-Martin oxidation of the alpha-hydroxyamide function of (XVII) gave rise to keto amide (XVIII). Finally, simultaneous cleavage from the resin and deprotection of the tert-butyl ester groups of (XVIII) by treatment with trifluoroacetic acid provided the title peptide amide.
| 【1】 Jones, P.S.; Kay, P.B.; Wilson, F.X.; Raynham, T.M.; Hurst, D.N. (Hoffmann-La Roche, Inc.); alpha-Ketoamide derivs.. US 6187905 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 47886 | tert-butyl (3S,6S,9S,12S,15S,18S)-3-amino-18-[(1S)-2-amino-1-hydroxy-2-oxoethyl]-6-[3-(tert-butoxy)-3-oxopropyl]-12-(tert-butyl)-15-isobutyl-9-(2-methylbenzyl)-4,7,10,13,16-pentaoxo-5,8,11,14,17-pentaazadocosan-1-oate | C46H77N7O11 | 详情 | 详情 | |
| (XVI) | 22262 | 4-(tert-butoxy)-4-oxobutyric acid | C8H14O4 | 详情 | 详情 | |
| (XVII) | 47887 | tert-butyl (6S,9S,12S,15S,18S,21S)-21-[(1S)-2-amino-1-hydroxy-2-oxoethyl]-6-[2-(tert-butoxy)-2-oxoethyl]-9-[3-(tert-butoxy)-3-oxopropyl]-15-(tert-butyl)-18-isobutyl-12-(2-methylbenzyl)-4,7,10,13,16,19-hexaoxo-5,8,11,14,17,20-hexaazapentacosan-1-oate | C54H89N7O14 | 详情 | 详情 | |
| (XVIII) | 47788 | (9R,10R)-9,10-dihydroxy-5-methoxy-4,8,8-trimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one | C16H18O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Friedel Crafts' condensation of phloroglucinol (I) with 3,3-dimethylacrylic acid (II) in the presence of boron trifluoride etherate gave the dihydroxy chromanone (III). Selective alkylation of the 7-hydroxyl group of (III) with iodomethane in the presence of K2CO3 furnished the methyl ether (IV). The carbonyl group of (IV) was subsequently reduced with NaBH4 in refluxing THF under basic conditions to produce chroman (V). The lactone ring of (VII) was then formed by a Pechmann reaction of (V) using ethyl acetoacetate (VI) and boron trifluoride to afford the tricyclic compound (VII). Dehydrogenation of (VII) employing DDQ in refluxing dioxan gave (VIII). The target 3'R,4'R-dihydroxylated derivative (IX) was obtained by Sharpless asymmetric dihydroxylation of (VIII) with hydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQ)2-PYR) as the chiral catalyst. Diol (IX) was finally esterified with (-)-S-camphanoyl chloride (X) to afford the title diester.
| 【1】 Takeuchi, Y.; McPhail, A.T.; Cosentino, L.M.; Lee, K.-H.; Xie, L.; Anti-AIDS agents.42. Synthesis and anti-HIV activity of disubstituted (3'R, 4'R)-3',4'-Di-O-(S)-camphanoyl-(+)-cis-khellactone analogues. J Med Chem 2001, 44, 5, 664. |
| 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) | 11799 | 1,3,5-Benzenetriol; Fluoroglucinol | 108-73-6 | C6H6O3 | 详情 | 详情 |
| (II) | 34677 | 3-methyl-2-butenoic acid | 541-47-9 | C5H8O2 | 详情 | 详情 |
| (III) | 22422 | 5,7-dihydroxy-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one | C11H12O4 | 详情 | 详情 | |
| (IV) | 47784 | 5-hydroxy-7-methoxy-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one | C12H14O4 | 详情 | 详情 | |
| (V) | 47785 | 7-methoxy-2,2-dimethyl-5-chromanol | C12H16O3 | 详情 | 详情 | |
| (VI) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
| (VII) | 47786 | 5-methoxy-4,8,8-trimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one | C16H18O4 | 详情 | 详情 | |
| (VIII) | 47787 | 5-methoxy-4,8,8-trimethyl-2H,8H-pyrano[2,3-f]chromen-2-one | C16H16O4 | 详情 | 详情 | |
| (IX) | 47788 | (9R,10R)-9,10-dihydroxy-5-methoxy-4,8,8-trimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one | C16H18O6 | 详情 | 详情 | |
| (X) | 16583 | (1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride; (-)-Camphanic chloride | 39637-74-6 | C10H13ClO3 | 详情 | 详情 |