Phenserine tartrate

合成路线:Hydrolysis of physostigmine (I) with either NaOMe in ethanol or NaOBu in refluxing butanol (better yield) gives eseroline (II),which is condensed with phenyl isocyanate (III) by means of NaOMe in benzene,Na in benzene or Na in ether/benzene.

合成路线:The title carbamate was prepared by condensation of (-)-eseroline (I) with 4-isopropylphenyl isocyanate in Et2O in the presence of a catalytic amount of Na.

参考文献标题:Substd.phenserines as specific inhibitors of acetylcholinesterase
文献作者:Brossi,A.; Brzostowska,M.; Rapoport,S.I.; Greig,N.; He,X.-S.(US Department of Health & Human Services)
参考来源:EP 0606366; JP 1995503703; US 5171750; WO 9306105


合成路线:Condensation of 5-methoxy-1,3-dimethyl-2,3-dihydro-1H-indol-2-one (IV) with 2-chloroacetonitrile (XI) by means of a chiral phase transfer catalyst gives 2-(5-methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-3-y)-acetonitrile,which is separated into enantiomers by chromatography.Reductocyclization of the (S)-enantiomer (XII) by means of Vitride affords (3aS)-N1-noresermethole (XIII),which is submitted to a reductive methylation to provide esermethole (X).O-demethylation of (X) by means of BBr3 or AlCl3 gives eseroline (II),which is finally condensed with phenyl isocyanate.

参考文献标题:Phenserine,a novel anticholinesterase related to physostigmine: Total synthesis and biological properties
文献作者:Greig,N.H.; Pei,X.-F.; Brossi,A.
参考来源:Aust J Chem 1996,49(2),171


合成路线:Hydrolysis of physostigmine (I) with either NaOMe in ethanol or NaOBu in refluxing butanol (better yield) gives eseroline (II),which is condensed with phenyl isocyanate (III) by means of NaOMe in benzene,Na in benzene or Na in ether/benzene.

参考文献标题:Phenserine and ring C hetero-analogs: Drug candidates for the treatment of Alzheimer's disease
文献作者:Greig,N.H.; Pei,X.F.; Soncrant,T.T.; Ingram,D.K.; Brossi,A.
参考来源:Med Res Rev 1995,15(1),3


合成路线:Hydrolysis of physostigmine (I) with either NaOMe in ethanol or NaOBu in refluxing butanol (better yield) gives eseroline (II),which is condensed with phenyl isocyanate (III) by means of NaOMe in benzene,Na in benzene or Na in ether/benzene.

合成路线:The title carbamate was prepared by condensation of (-)-eseroline (I) with 4-isopropylphenyl isocyanate in Et2O in the presence of a catalytic amount of Na.

参考文献标题:Phenylcarbamates of (-)-eseroline,(-)-N1-noreseroline and (-)-physovenol: Selective inhibitors of acetyl and,or butyrylcholinesterase
文献作者:Brzostowska,M.; et al.
参考来源:Med Chem Res 1992,2(4),238


合成路线:Condensation of 5-methoxy-1,3-dimethyl-2,3-dihydro-1H-indol-2-one (IV) with 2-chloro-N,N-dimethylethyl-amine (V) by means of NaNH2 in toluene gives 3-[2-(di-methylamino)ethyl]-5-methoxy-1,3-dimethyl-2,3-dihydro-1H-indol-2-one (VI),which is reduced with Vitride (sodium bis(2-methoxyethoxy)aluminum dihydride) in toluene to yield the secondary alcohol (VII).Optical resolution of (VII) by means of (+)-2,3-di-O-(p-toluoyl)tartaric acid provides the (2S,3S)-diastereomer (VIII),which by reaction with methyl iodide in ethyl ether affords the ammonium salt (IX).Cyclization of compound (IX) by means of methylamine in acetonitrile provides esermethole (X),the methyl ether of eseroline,which is demethylated by means of BBr3 in dichloromethane to give eseroline (II).Finally,eseroline is condensed with phenyl isocyanate (VIII) by means of Na in ethyl ether.

参考文献标题:125.Total synthesis of racemic and optically active compounds related to physostigmine and ring-C heteroanalogues from 3-[2'-(dimethylamino)ethyl]-2,3-dihydro-5-methoxy-1,3-dimethyl-1H-indol-2-ol
文献作者:Brossi,A.; Bi,S.; Greig,N.H.; Pei,X.-F.
参考来源:Helv Chim Acta 1994,77(5),1412


合成路线:Hydrolysis of physostigmine (I) with either NaOMe in ethanol or NaOBu in refluxing butanol (better yield) gives eseroline (II),which is condensed with phenyl isocyanate (III) by means of NaOMe in benzene,Na in benzene or Na in ether/benzene.

参考文献标题:New analogs of physostigmine: Alternative drugs for Alzheimer's disease?
文献作者:Marta,M.; Castellano,C.; Oliverio,A.; Pavone,F.; Pagella,P.G.; Brufani,M.; Pomponi,M.
参考来源:Life Sci 1988,43(23),1921