66761-54-4Relevant academic research and scientific papers
Synthesis and Biological Activity of Octaketides from the Cytosporone Family
von Delius, Max,Le, Christine M.,Ellinger, Bernhard,Kuzikov, Maria,Gul, Sheraz,Dong, Vy M.
, p. 975 - 981 (2017)
Cytosporone B and its simple analogues (e. g., amoitone B) were recently identified as unique agonists for nuclear orphan receptor Nur77. In this study, we have developed an aldehyde C-H activation method for preparing natural and designer analogues from the cytosporone family. In addition, a comprehensive investigation of the compounds’ biological activities and pharmacological liabilities has been conducted and new structure activity relationships (SAR) were derived from the data. Most notably, we found that increased cytotoxicity can be obtained by virtue of fluorine substitution on the hydrophobic acyl chain.
Rhodium-phosphoramidite catalyzed alkene hydroacylation: Mechanism and octaketide natural product synthesis
Von Delius, Max,Le, Christine M.,Dong, Vy M.
supporting information, p. 15022 - 15032 (2012/11/06)
We describe a method that allows salicylaldehyde derivatives to be coupled with a wide range of unactivated alkenes at catalyst loadings as low as 2 mol %. A chiral phosphoramidite ligand and the precise stoichiometry of heterogeneous base are key for high catalytic activity and linear regioselectivity. This protocol was applied in the atom- and step-economical synthesis of eight biologically active octaketide natural products, including anticancer drug candidate cytosporone B. Mechanistic studies provide insight on parameters affecting decarbonylation, a side reaction that limits the turnover number for catalytic hydroacylation. Deuterium labeling studies show that branched hydride insertion is fully reversible, whereas linear hydride insertion is largely irreversible and turnover-limiting. We propose that ligand (R a,R,R)-SIPHOS-PE effectively suppresses decarbonylation, and helps favor a turnover-limiting insertion, by lowering the barrier for reductive elimination in the linear-selective pathway. Together, these factors enable high reactivity and regioselectivity.
Synthesis of chlorohomophthalic acids, key intermediates in the synthesis of chlorinated isocoumarins
Joseph, Augustine R.,Kumbhar, Virendra B.,Ranade, Anup A.,Paradkar, Madhusudan V.
, p. 91 - 93 (2008/02/04)
Efficient synthesis of chlorohomophthalic acids (6) and (7), key intermediates in the synthesis of chlorinated isocoumarins (3) and (4) is described.
Conformationally restricted congeners of dopamine derived from octahydrobenzo[g]quinoline and octahydrobenzo[f]quinoline
Cannon,Hamer,Ilhan,Bhatnagar,Long
, p. 190 - 195 (2007/10/02)
Series of N-alkylated derivatives of trans-octahydrobenzo[g]quinoline and of cis- and trans-octahydrobenzo[f]quinoline were prepared for pharmacological testing as congeners of 2-amino-5,7-dihydroxytetralin, which elicits dopaminergic effects in a variety
