4-Methyldicamphanoylkhellactone, PA-344, 4-Methyl-DCK, -Drug Synthesis Database

【结构式】

【药物名称】4-Methyldicamphanoylkhellactone, PA-344, 4-Methyl-DCK

【化学名称】Bis[(1S,1'S,4R,4'R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylic acid] (9R,10R)-4,8,8-trimethyl-2-oxo-9,10-dihydro-2H,8H-benzo[1,2-b:3,4-b']dipyran-9,10-diyl ester
　　　　　　(9R,10R)-4,8,8-Trimethyl-9,10-bis[4(R),7,7-trimethyl-3-oxo-2-oxabicyclo[2,2,1]heptan-1(S)-ylcarbonyloxy]-9,10-dihydro-2H,8H-benzo[1,2-b:3,4-b']dipyran-2-one
　　　　　　3',4'-Di-O-[(-)-(S)-camphanoyl]-4-methyl-(3'R,4'R)-cis-khellactone

【CA登记号】214330-43-5

【分子式】C₃₅H₄₀O₁₁

【分子量】636.70245

【开发单位】Biotech Research Laboratories (Originator), University of North Carolina (Originator), Panacos (Licensee)

【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY

合成路线1

4-Methyl-7-hydroxycoumarin (I) was alkylated with 3-chloro-3-methyl-1-butyne (II) in the presence of K2CO3 and KI to afford the corresponding aryl propargyl ether (III). Claisen rearrangement of (III) in refluxing diethylaniline furnished the tricyclic system (IV). The target 3'R,4'R-dihydroxylated derivative (V) was obtained by Sharpless asymmetric dihydroxylation of (IV) with hydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQ)2-PYR) as the chiral catalyst. Diol (V) was finally esterified with (-)-S-camphanoyl chloride (VI) to afford the title diester.

参考文献中间体

【1】 Xie, L.; Takeuchi, Y.; Cosentino, L.M.; Lee, K.-H.; Anti-AIDS agent 33. Synthesis and anti-HIV activity of mono-methyl substituted 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogues. Bioorg Med Chem Lett 1998, 8, 16, 2151.
【2】 Takeuchi, Y.; Xie, L.; Lee, K.-H.; Cosentino, L.M.; Anti-AIDS agents. 37.(1) synthesis and structure-activity relationships of (3'R,4'R)-(+)-cis-khellactone derivatives as novel potent anti-HIV agents. J Med Chem 1999, 42, 14, 2662.

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)	47997	7-hydroxy-4-methyl-2H-chromen-2-one	90-33-5	C₁₀H₈O₃	详情	详情
(II)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(III)	47998	7-[(1,1-dimethyl-2-propynyl)oxy]-4-methyl-2H-chromen-2-one		C₁₅H₁₄O₃	详情	详情
(IV)	47999	4,8,8-trimethyl-2H,8H-pyrano[2,3-f]chromen-2-one		C₁₅H₁₄O₃	详情	详情
(V)	48000	(9R,10R)-9,10-dihydroxy-4,8,8-trimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one		C₁₅H₁₆O₅	详情	详情
(VI)	41620	(1R,4S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride		C₁₀H₁₃ClO₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)