title: SmI2-induced cyclizations and their applications in natural product synthesis.
abstract: Since the isolation of brevetoxin-B, a red tide toxin, many bioactive marine natural products featuring synthetically challenging trans-fused polycyclic ether ring systems have been reported. We have developed SmI(2)-induced cyclization of beta-alkoxyacrylate with aldehyde, affording 2,6-syn-2,3-trans-tetrahydropyran (THP) or 2,7-syn-2,3-trans-oxepane with complete stereoselection, as a key reaction of efficient iterative and bi-directional strategies for the construction of these polycyclic ethers. This reaction is also applicable to the synthesis of 3-, 5-, and 6-methyl-THPs and 3,5-dimethyl-THP. The synthesis of 2-methyl- and 2,6-dimethyl-THPs was accomplished by means of a unique methyl insertion. Recently, the SmI(2)-induced cyclization was extended to similar reactions using beta-alkoxyvinyl sulfone and sulfoxide. Reaction of (E)- and (Z)-beta-alkoxyvinyl sulfone-aldehyde afforded 2,6-syn-2,3-trans- and 2,6-syn-2,3-cis- THPs, respectively. Reaction of (E)-beta-alkoxyvinyl (R)- and (S)-sulfoxides gave 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-THPs, respectively. Reaction of (Z)-beta-alkoxyvinyl (R)-sulfoxides gave 2,6-syn-2,3-cis-THP and an olefinic product, while that of (Z)-beta-alkoxyvinyl (S)-sulfoxide afforded a mixture of many products. These SmI(2)-induced cyclizations have been applied to the total syntheses of various natural products, including brevetoxin-B, mucocin, pyranicin, and pyragonicin. Synthetic studies on gambierol and maitotoxin are also introduced.
authors.affiliation: Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo162-8601, Japan. nakata@rs.kagu.tus.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakata
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002922:Ciguatoxins / Q000138:chemical synthesis / Q000737:chemistry; D003500:Cyclization; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry; D007454:Iodides / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry; D008387:Marine Toxins / Q000138:chemical synthesis / Q000737:chemistry; D035964:Oxocins / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry; D012493:Samarium / Q000737:chemistry*; D000095702:Polyether Toxins
chemical_list: D001688:Biological Products; D002922:Ciguatoxins; D004987:Ethers; D006576:Heterocyclic Compounds, 4 or More Rings; D007454:Iodides; D007783:Lactones; D008387:Marine Toxins; D035964:Oxocins; D011108:Polymers; D011714:Pyrans; D012493:Samarium; C489035:brevenal (polyether); C435770:gambierol; C413144:mucocin; C409729:hemibrevetoxin B; C043466:brevetoxin B; D000095702:Polyether Toxins; C020394:maitotoxin; C409809:samarium diiodide