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.
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.
Zou
Yefen
Y
Department of Chemistry MS 015, Brandeis University, Waltham, Massachusetts 02454-9110.
Lobera
Mercedes
M
Snider
Barry B
BB
D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry*; D001572:Benzofurans / Q000138:chemical synthesis*; D004852:Epoxy Compounds / Q000737:chemistry; D005363:Ficusin / Q000138:chemical synthesis*; D011564:Furocoumarins / Q000138:chemical synthesis*; D008968:Molecular Conformation; D018716:Molecular Mimicry
D000447:Aldehydes; D001572:Benzofurans; D004852:Epoxy Compounds; D011564:Furocoumarins; C499754:avicenol A; C499752:brosimacutin G; C499751:vaginidiol; C499753:smyrindiol; C011659:angelicin; D005363:Ficusin