64395-07-9Relevant articles and documents
Synthesis, anti-GABA activity and preferred conformation of bicuculline and norbicuculline enantiomers
Kardos,Blandl,Luyen,Doernyei,Gacs-Baitz,Simonyi,Cash,Blasko,Szantay
, p. 761 - 765 (2007/10/03)
Synthesis of erythro-(±)-[1SR,9RS]-norbicuculline and threo-(±)-[1SR,9SR]-noradlumidine from piperonal was performed using Bischler-Napieralski cyclization as a key step. Resolution gave rise to (+)-[1S,9R]-norbicuculline ([1S,9R] norBIC) and (-)-[1R,9S]-norbicuculline ([1R,9S] norBIC) in >99.5% enantiomeric purity. Bicuculline enantiomers were readily obtained by methylation of the latter products. [1S,9R]BIC was about 70 times more potent than [1R,9S]BIC as an inhibitor of GABA(A) receptor binding and was about 100 and 900 times more potent than [1S,9R] norBIC at pH 7.1 and 5.0 respectively. Similarly, [1S,9R] norBIC was much less potent than [1S,9R]BIC as an inhibitor of GABA-specific 36Cl- ion flux. The observed increase of about two orders of magnitude in the in vitro biological activity caused by N2-CH3 substitution in [1S,9R] norBIC was attributed to different conformations for erythro- and nor-erythro-bicucullines indicated by 1H nuclear Overhauser enhancements of [1S,9R]BIC and [1S,9R] norBIC.
Total Synthesis of (+/-)-Chelidonine
Cushman, Mark,Choong, Tung-Chung,Valko, Joseph T.,Koleck, Mary P.
, p. 5067 - 5073 (2007/10/02)
Condensation of the Schiff base 8 with 3,4-(methylenedioxy)homophthalic anhydride (13) was exploited as the key step in a total synthesis of the benzophenanthridine alkaloid (+/-)-chelidonine (1).A variety of reaction conditions were investigated in order to maximize the production of the desired thermodynamically less stable cis diastereomer.A method was devised for the conversion of 24 to its acid chloride without production of the indenoisoquinoline 30.The migration of an aromatic ring was observed on treatment of the diazo ketone 26 with acid.This reaction is reminiscent of the Hayashi rearrangement.
