Synthesis of 2,3-dihydro-3-hydroxy-2-hydroxylalkylbenzofurans from epoxy aldehydes. One-step syntheses of brosimacutin G, vaginidiol, vaginol, smyrindiol, xanthoarnol, and avicenol A. Biomimetic syntheses of angelicin and psoralen
Synthesis of 2,3-dihydro-3-hydroxy-2-hydroxylalkylbenzofurans from epoxy aldehydes. One-step syntheses of brosimacutin G, vaginidiol, vaginol, smyrindiol, xanthoarnol, and avicenol A. Biomimetic syntheses of angelicin and psoralen
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DOI：
10.1021/jo047974k
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发表时间：
2005-03-04
影响因子：
3.6
通讯作者：
Snider, BB
中科院分区：
文献类型：
--
作者：
Zou, YF;Lobera, M;Snider, BB
我们已经开发了两种实用的一步合成2,3-二氢-3-羟基-2-羟基烷基苯并呋喃的方法，这些方法是由现成的光学纯α， β -环氧醛合成的。缺电子间苯二酚与环氧醛在DMF中的Cs2CO3或在MeOH中的KOH/CaCl2反应生成加合物13、16、18、20、21和溴化氢G （6t）。将乙酰氧基碘香豆素35d、40和乙酰氧基溴萘41低温卤素-金属交换制备的格氏试剂加入环氧醛(S)-26中，首次合成阴道二醇（7c）、阴道醇（7t）、三甲醚二醇（8c）、黄酮醇（8t）和阿维烯醇A （9t）。酸催化的阴道二醇或阴道醇裂解提供当归素，而三香英二醇或黄原醇的裂解提供补骨脂素。在这两种情况下，反式异构体的分裂速度仅为顺式异构体的两倍，可能是通过共同的苯基阳离子的中间作用。这可能对angelicin和补骨脂素的生物合成有影响。
[GRAPHICS]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.