布格呋喃体内代谢产物的合成

基金项目: 国家“重大新药创制”科技重大专项资助项目(No.2010ZX09401405-001)

Synthesis of a new metabolite of buagarofuran(AF-5)

摘要: 布格呋喃(AF-5)是已报道的一类具有抗焦虑活性的精神治疗药物之一，其结构由一个沉香呋喃环骨架和一个正丁基侧链组成。临床药代研究发现其新的代谢产物，推测其结构可能为烷烃链端基的羰酸化产物。为了确证其结构，以中间体(4aR，7R，8aR)-8a-羟基-7-(2-羟丙基-2-基)-4a-甲基八氢萘-2(1氢)-酮为原料，经6步反应，成功合成了目标化合物，总收率16.7%。化合物的结构均经NMR和MS确证。
- 布格呋喃 /
- AF-5 /
- 代谢产物 /
- 合成 /
- 结构鉴定
Abstract: It has been reported that buagarofuran(AF-5)as an anxiolytic drug. It possesses a structural feature including α-agarofuran and the n-butyl side chain. Recently, there is a new metabolite found in clinical study, which is hypothesized that the n-butyl side chain has been oxidized to carboxylic acid. In order to confirm its structure, the target compound was prepared from(4aR, 7R, 8aR)-8a-hydroxy-7-(2-hydroxypropan-2-yl)-4a-methyloctahydronaphthalen-2(1H)-one in a six-step reaction with an overall yield of 16. 7%. The structure is confirmed by NMR and MS.
- buagarofuran /
- AF-5 /
- metabolite /
- synthesis /
- structural identification

[1]	Guo JY.Agarofuan derivatives,their preparation,pharmaceutical composition containing them and their use as medicine:CN,98122447[P].2002-11-26.
[2]	Guo JY. New agarofuran derivatives, their preparations, pharma- 　　 ceutical compositions containing them and their uses as medicaments:CN,00108339[P].2000-05-12.
[3]	Guo JY.Dehydrobaimuxinol derivatives use as medicaments for treating or preventing regressive diseases of brain:CN,00108338[P].2000-05-12.
[4]	Ji M.Synthesis of metablism product of cloxazolam 7-chloro-5-o-chlorophenyl -1,3-dihydro-1,4-benzodiazepin-2-one[J].J China Pharm Univ(中国药科大学学报),1993,24(3):180-181.
[5]	Li C,Zhang WY,Guo JY,et al.Studies on agarofurans VIII.Synthesis of the metabolites of 4-butyl-α-agarofuran[J].Chin Chem Lett,2002,13(1):19-22.
[6]	Li C,Yin DL,Huang HQ,et al.New stereoselective synthesis of 4-butyl-α-agarofuran[J].Chin Chem Lett,2003,14(9):881-882.
[7]	Chandrasekhar S,Babu GSK,Mohapatra DK.Practical syntheses of(2S)-R207910 and(2R)-R207910[J].Eur J Org Chem,2011,2011(11):2057-2061.
[8]	Berthelette C.Nitric oxide releasing prodrugs of diaryl-2-(5H)-furanones as cyclooxygenase-2 inhibitors:US,176331[P].2004-09-09.