39240-15-8Relevant articles and documents
Asymmetric total synthesis of mycoleptodiscin A
Zhou, Shupeng,Chen, Hao,Luo, Yijie,Zhang, Wenhao,Li, Ang
, p. 6878 - 6882 (2015)
The first total synthesis of mycoleptodiscin A, a structurally unusual indolosesquiterpenoid possessing an ortho-benzoquinone motif, has been accomplished. A sulfone alkylation coupled two readily available fragments to give an aryl triene intermediate. The tetracyclic core of the molecule was assembled through a highly enantioselective iridium-catalyzed polyene cyclization. The benzylic homologation was achieved by a cationic cyanation. The indole motif was constructed via a copper-mediated intramolecular C-N bond formation at a late stage.
Hydrazide-Catalyzed Polyene Cyclization: Asymmetric Organocatalytic Synthesis of cis-Decalins
Plamondon, Samuel J.,Warnica, Josephine M.,Kaldre, Dainis,Gleason, James L.
supporting information, p. 253 - 258 (2019/11/28)
Polyene cyclizations offer rapid entry into terpenoid ring systems. Although enantioselective cyclizations of (E)-polyenes to form trans-decalin ring systems are well precedented, highly enantioselective cyclizations of (Z)-polyenes to form the correspond
Discovery of structurally simplified analogs of colchicine as an immunosuppressant
Chang, Dong-Jo,Kim, Wan-Joo
, p. 3121 - 3125 (2014/06/24)
We have discovered a new class of colchicine-derived therapeutic agents for immune diseases including rejection of organ-transplantation and autoimmune disease. Compound 2, which had been developed to overcome poor pharmacokinetic properties of compound 1, a first-generation colchicine analog, turned out to show toxicity such as intestinal toxicity and loss of weight during in vivo tests. The deletion of 7-carboxamide group and middle ring-truncation in colchicine allowed us to have structurally simplified analogs with strong immunosuppressive activity. Herein, we report non-alkaloid tricyclic compound 7 and 12 as immunosuppressants which exhibited a strong immunosuppressive in vivo efficacy on the T-dependent antibody response, the Zymosan A-induced arthritis model and the Carrageenan-induced edema model. Compound 7 and 12 revealed less toxicity than the previous lead compound 2, and their minimum lethal doses (MLD) were proved to exceed 100 mg/kg.
Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer
Sun, Bin,Hoshino, Juma,Jermihov, Katie,Marler, Laura,Pezzuto, John M.,Mesecar, Andrew D.,Cushman, Mark
experimental part, p. 5352 - 5366 (2010/09/05)
A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC50 0.59 μM) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC50 70 nM) and 84 (IC50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC 50 1.7 μM and 0.27 μM, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.
