Zou Yefen, Lobera Mercedes, Snider Barry B
Department of Chemistry MS 015, Brandeis University, Waltham, Massachusetts 02454-9110.
J Org Chem. 2005 Mar 4;70(5):1761-70. doi: 10.1021/jo047974k.
We have developed two practical one-step syntheses of 2,3-dihydro-3-hydroxy-2-hydroxyalkylbenzofurans from readily available optically pure alpha,beta-epoxy aldehydes. Electron-deficient resorcinols react with epoxy aldehydes using either Cs2CO3 in DMF or KOH/CaCl2 in MeOH to give adducts 13, 16, 18, 20, 21, and brosimacutin G (6t). Grignard reagents prepared by low-temperature halogen-metal exchange of acetoxy iodocoumarins 35d and 40 and acetoxy bromonaphthalene 41 add to epoxy aldehyde (S)-26 to complete the first syntheses of vaginidiol (7c), vaginol (7t), smyrindiol (8c), xanthoarnol (8t), and avicenol A (9t). Acid-catalyzed fragmentation of vaginidiol or vaginol provides angelicin, while that of smyrindiol or xanthoarnol affords psoralen. In both cases, the trans isomers fragment only twice as fast as the cis isomers, possibly through the intermediacy of a common benzylic cation. This may have implications for the biosynthesis of angelicin and psoralen.
我们已经从容易获得的光学纯α,β-环氧醛开发出两种实用的一步合成2,3-二氢-3-羟基-2-羟烷基苯并呋喃的方法。缺电子间苯二酚与环氧醛反应，使用碳酸铯在N,N-二甲基甲酰胺中或氢氧化钾/氯化钙在甲醇中反应，得到加合物13、16、18、20、21和溴西马库汀G（6t）。通过乙酰氧基碘香豆素35d和40以及乙酰氧基溴萘41的低温卤素-金属交换制备的格氏试剂加成到环氧醛（S）-26上，完成了阴道二醇（7c）、阴道醇（7t）、叙利亚二醇（8c）、黄檀醇（8t）和白骨壤醇A（9t）的首次合成。阴道二醇或阴道醇的酸催化裂解生成当归素，而叙利亚二醇或黄檀醇的酸催化裂解生成补骨脂素。在这两种情况下，反式异构体的裂解速度仅为顺式异构体的两倍，可能是通过一个共同的苄基阳离子中间体。这可能对当归素和补骨脂素的生物合成有影响。
