2173-69-5Relevant articles and documents
Dienolates of Cycloalkenones and α,β-Unsaturated Esters Form Diels–Alder Adducts by a Michael/Michael-Tandem Reaction Rather Than in One Step
Loesche, Ann-Christine,Brückner, Reinhard
, p. 562 - 573 (2019)
α,β-Unsaturated esters and lithium 1,3-dien-2-olates are known to furnish bicyclic lithium enolates by anionic Diels–Alder reactions. However, in principle, the respective products might form not only in a single step but also in two consecutive – or “tandem” – Michael additions, the first of which occurs intermolecularly, the second intramolecularly. Three cyclic lithium dienolates and four esters with a stereogenic Cα=Cβ bond reacted to give Diels–Alder adducts (10 times) or failed to react (2 times). Seven of the reactive combinations furnished adducts wherein the configuration of the former ester moiety had in part inverted. This precludes concerted pathways as their origins. This was a surprise since donors at C-2 of the 1,3-diene accelerate normal electron-demand Diels–Alder reactions in the order alkyl ⊕O? being a far better donor still, it is not obvious why the mechanism is non-concerted rather than concerted (and still more asynchronous).
Discovery of Salidroside-Derivated Glycoside Analogues as Novel Angiogenesis Agents to Treat Diabetic Hind Limb Ischemia
Liu, Caiping,Han, Jingxuan,Marcelina, Olivia,Nugrahaningrum, Dyah Ari,Huang, Song,Zou, Meijuan,Wang, Guixue,Miyagishi, Makoto,He, Yun,Wu, Shourong,Kasim, Vivi
, p. 135 - 162 (2022/01/14)
Therapeutic angiogenesis is a potential therapeutic strategy for hind limb ischemia (HLI); however, currently, there are no small-molecule drugs capable of inducing it at the clinical level. Activating the hypoxia-inducible factor-1 (HIF-1) pathway in skeletal muscle induces the secretion of angiogenic factors and thus is an attractive therapeutic angiogenesis strategy. Using salidroside, a natural glycosidic compound as a lead, we performed a structure-activity relationship (SAR) study for developing a more effective and druggable angiogenesis agent. We found a novel glycoside scaffold compound (C-30) with better efficacy than salidroside in enhancing the accumulation of the HIF-1α protein and stimulating the paracrine functions of skeletal muscle cells. This in turn significantly increased the angiogenic potential of vascular endothelial and smooth muscle cells and, subsequently, induced the formation of mature, functional blood vessels in diabetic and nondiabetic HLI mice. Together, this study offers a novel, promising small-molecule-based therapeutic strategy for treating HLI.
Structure-Guided Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease
Rathnayake, Athri D.,Kim, Yunjeong,Dampalla, Chamandi S.,Nguyen, Harry Nhat,Jesri, Abdul-Rahman M.,Kashipathy, Maithri M.,Lushington, Gerald H.,Battaile, Kevin P.,Lovell, Scott,Chang, Kyeong-Ok,Groutas, William C.
, p. 11945 - 11963 (2020/11/26)
Acute gastroenteritis caused by noroviruses has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The disease impacts most severely immunocompromised patients, the elderly, and children. The current lack of approved vaccines and small-molecule therapeutics for the treatment and prophylaxis of norovirus infections underscores the need for the development of norovirus-specific drugs. The studies described herein entail the use of the gem-dimethyl moiety as a means of improving the pharmacological activity and physicochemical properties of a dipeptidyl series of transition state inhibitors of norovirus 3CL protease, an enzyme essential for viral replication. Several compounds were found to be potent inhibitors of the enzyme in biochemical and cell-based assays. The pharmacological activity and cellular permeability of the inhibitors were found to be sensitive to the location of the gem-dimethyl group.
Aerobic C-C and C-O bond formation reactions mediated by high-valent nickel species
Gómez, Laura,Mirica, Liviu M.,Planas, Oriol,Rath, Nigam P.,Ribas, Xavi,Smith, Sofia M.
, p. 10366 - 10372 (2019/11/20)
Nickel complexes have been widely employed as catalysts in C-C and C-heteroatom bond formation reactions. While Ni(0), Ni(i), and Ni(ii) intermediates are most relevant in these transformations, recently Ni(iii) and Ni(iv) species have also been proposed to play a role in catalysis. Reported herein is the synthesis, detailed characterization, and reactivity of a series of Ni(ii) and Ni(iii) metallacycle complexes stabilized by tetradentate pyridinophane ligands with various N-substituents. Interestingly, while the oxidation of the Ni(ii) complexes with various other oxidants led to exclusive C-C bond formation in very good yields, the use of O2 or H2O2 as oxidants led to formation of appreciable amounts of C-O bond formation products, especially for the Ni(ii) complex supported by an asymmetric pyridinophane ligand containing one tosyl N-substituent. Moreover, cryo-ESI-MS studies support the formation of several high-valent Ni species as key intermediates in this uncommon Ni-mediated oxygenase-type chemistry.
