1198596-71-2Relevant academic research and scientific papers
Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity
Gadhiya, Satishkumar,Madapa, Sudharshan,Kurtzman, Thomas,Alberts, Ian L.,Ramsey, Steven,Pillarsetty, Nagavara-Kishore,Kalidindi, Teja,Harding, Wayne W.
, p. 2060 - 2071 (2016/04/20)
Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (±)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (±)-stepholidine, were synthesized and evaluated for affinity at dopamine and σ receptors in order to evaluate effects on D3 and σ2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and σ2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for σ2 receptors as well as σ2 versus σ1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and σ receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds.
A divergent route to 9,10-oxygenated tetrahydroprotoberberine and 8-oxoprotoberberine alkaloids: Synthesis of (±)-isocorypalmine and oxypalmatine
Gadhiya, Satish,Ponnala, Shashikanth,Harding, Wayne W.
, p. 1227 - 1231 (2015/03/05)
A new route, which is germane to the synthesis of 9,10-oxygenated tetrahydroprotoberberines and 8-oxoprotoberberines is described. The route features the use of a diester (14) generated from reaction of dimethylmalonate with an aryl halide in the presence of n-butyllithium. The amide 17 prepared in subsequent steps is a versatile precursor for the synthesis of tetrahydroprotoberberine and 8-oxoprotoberberine scaffolds using standard high-yielding reactions. In this manner, (±)-isocorypalmine and oxypalmatine have been synthesized in 23% and 22% yields, respectively.
Synthesis of the carbon skeleton of the griseorhodins
Atkinson, Darcy J.,Furkert, Daniel P.,Brimble, Margaret A.
, p. 91 - 101 (2015/02/02)
A synthetic strategy to access the carbon skeleton of the griseorhodin family of natural products has been developed. The key step involved the acid-mediated spirocyclisation of a highly functionalised dihydroxyketone. The delicate electronic balance betw
An efficient formal synthesis of the human telomerase inhibitor (±)-γ-rubromycin
Rathwell, Dominea C. K.,Yang, Sung-Hyun,Tsang, Kit Y.,Brimble, Margaret A.
scheme or table, p. 7996 - 8000 (2010/01/16)
Balancing act: The correct balance of electronic factors in the naphthazarin and isocoumarin fragments facilitates the acid-mediated spiroketalization step to afford the key densely functionalized spiroketal (see picture; EOM=ethoxymethyl) in the formal s
