title: Highly efficient and concise synthesis of both antipodes of SB204900, clausenamide, neoclausenamide, homoclausenamide and zeta-clausenamide. Implication of biosynthetic pathways of Clausena alkaloids.
abstract: The synthesis of both antipodes of N-methyl-N-[(Z)-styryl]-3-phenyloxirane-2-carboxamide (SB204900), clausenamide, neoclausenamide, homoclausenamide and zeta-clausenamide have been accomplished using (2S,3R)- and (2R,3S)-3-phenyloxirane-2-carboxamides as the starting materials, and SB204900 was found to be a common precursor to other N-heterocyclic clausena alkaloids. Mediated by Brønsted acids under different conditions, for example, SB204900 underwent efficient and diverse alkene-epoxide cyclization, enamide-epoxide cyclization and arene-epoxide cyclization reactions to produce the five-membered N-heterocyclic neoclausenamide, its 6-epimer, the six-membered N-heterocyclic homoclausenamide and the eight-membered N-heterocyclic zeta-clausenamide, respectively, in good to excellent yields. Regiospecific oxidation of neoclausenamide and its 6-epimer afforded neoclausenamidone. Enolization of neoclausenamidone in the presence of LiOH and the subsequent protonation under kinetic conditions at -78 degrees C led to the epimerization of neoclausenamidone into clausenamidone. Reduction of clausenamidone using NaBH(4) furnished clausenamide in high yield.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Luo
authors.initials: L
authors.lastname: Yang
authors.forename: De-Xian
authors.initials: DX
authors.lastname: Wang
authors.forename: Qi-Yu
authors.initials: QY
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Zhi-Tang
authors.initials: ZT
authors.lastname: Huang
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis / Q000138:chemical synthesis*; D032701:Biomimetics; D054700:Clausena / Q000378:metabolism*; D005027:Ethylene Oxide / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis* / Q000378:metabolism; D017705:Lignans / Q000096:biosynthesis / Q000138:chemical synthesis*; D011728:Pyridones / Q000138:chemical synthesis* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D007769:Lactams; D007783:Lactones; D017705:Lignans; D011728:Pyridones; C543053:homoclausenamide; C053048:clausenamide; C112852:SB 204990; D005027:Ethylene Oxide