1396756-70-9Relevant academic research and scientific papers
Total Synthesis and Cytotoxic Activity of 5′-Hydroxyzearalenone and 5′β-Hydroxyzearalenone
Thiraporn, Aticha,Rukachaisirikul, Vatcharin,Iawsipo, Panata,Somwang, Tatiyar,Tadpetch, Kwanruthai
, p. 7133 - 7147 (2017)
An efficient and convergent synthesis of 5′-hydroxyzearalenone and 5′β-hydroxyzearalenone, 14-membered β-resorcylic acid lactone (RAL) natural products, has been achieved in a longest linear sequence of 19 steps, and a total of 29 steps, starting from commercially available 5-hexen-1-ol and methyl 2-(3,5-dimethoxyphenyl)acetate. The key features of our synthesis include a Jacobsen hydrolytic kinetic resolution, a Mitsunobu esterification and (an E)-selective ring-closing metathesis (RCM). Our synthesis also highlights the utility of the acetal protecting group for the resorcylate moiety, and its compatibility with RCM reactions for the synthesis of 14-membered RALs. The cytotoxic activity of both synthetic compounds was evaluated against seven human cancer cell lines. 5′-Hydroxyzearalenone shows more potent cytotoxic activity against most of the cancer cell lines tested than its epimer, 5′β-hydroxyzearalenone. Both compounds show significant cytotoxic activity against the C33A cervical cancer cell line, with IC50 values of 21.33 ± 6.43 μm and 16.00 ± 12.17 μm, respectively.
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.
