1.Asymmetric Total Synthesis of Sarpagine-Related Indole Alkaloids Hydroxygardnerine, Hydroxygardnutine, Gardnerine, (E)-16-epi-Normacusine B, and Koumine.
Kitajima M1, Watanabe K1, Maeda H1, Kogure N1, Takayama H1. Org Lett. 2016 Apr 15;18(8):1912-5. doi: 10.1021/acs.orglett.6b00661. Epub 2016 Apr 1.
Sarpagine-related indole alkaloids (-)-hydroxygardnerine, (+)-hydroxygardnutine, (-)-gardnerine, (+)-(E)-16-epi-normacusine B, and (-)-koumine were divergently synthesized via a common intermediate possessing a piperidine ring with an exocyclic (E)-ethylidene side chain, which was constructed by a gold(I)-catalyzed 6-exo-dig cyclization strategy.
2.New enolate-carbodiimide rearrangement in the concise synthesis of 6-amino-2,3-dihydro-4-pyridinones from homoallylamines.
Kuznetsov NY1, Tikhov RM1, Godovikov IA1, Khrustalev VN2, Bubnov YN3. Org Biomol Chem. 2016 Apr 15. [Epub ahead of print]
Three-step synthesis of 6-amino-2,3-dihydro-4-pyridinones from homoallylamines involving NBS-mediated cyclization of N-(3-butenyl)ureas to 6-(bromomethyl)-2-iminourethanes, dehydrohalogenation and a novel rearrangement as a key step has been developed. The scope and limitations of the method, as well as the mechanism of the rearrangement, supported by kinetic studies and the isolation of N-(1-adamantyl)carbodiimide, are discussed. The final products, imino-analogues of well known piperidine-2,4-diones, are promising building blocks in the synthesis of bio-/pharmacological compounds.
3.Asymmetric Formal Aza-Diels-Alder Reaction of Trifluoromethyl Hemiaminals with Enones Catalyzed by Primary Amines.
Zhang S1, Cha L1, Li L1, Hu Y1, Li Y1, Zha Z1, Wang Z1. J Org Chem. 2016 Apr 15;81(8):3177-87. doi: 10.1021/acs.joc.6b00087. Epub 2016 Apr 7.
A primary amine-catalyzed asymmetric formal aza-Diels-Alder reaction of trifluoromethyl hemiaminals with enones was developed via a chiral gem-diamine intermediate. This novel protocol allowed facile access to structurally diverse trifluoromethyl-substituted piperidine scaffolds with high stereoselectivity. The utility of this method was further demonstrated through a concise approach to biologically active 4-hydroxypiperidine. More importantly, a stepwise mechanism involving an asymmetric induction process was proposed to rationalize the positive correlation between the chirality of the gem-diamine intermediate and the formal aza-Diels-Alder product.
4.Protective Effect of Tempol on Buthionine Sulfoximine-Induced Mitochondrial Impairment in Hippocampal Derived HT22 Cells.
Salvi A1, Patki G1, Khan E1, Asghar M1, Salim S1. Oxid Med Cell Longev. 2016;2016:5059043. doi: 10.1155/2016/5059043. Epub 2016 Mar 16.
Using a simulated oxidative stress model of hippocampus-derived immortalized cell line (HT22), we report that prooxidant buthionine sulfoximine (BSO, 1 mM, 14 h), without adversely affecting cell viability or morphology, induced oxidative stress by inhibiting glutathione synthesis. BSO treatment also significantly reduced superoxide dismutase (SOD) activity (p < 0.05) and significantly lowered total antioxidant capacity (p < 0.001) in HT22 cells when compared to vehicle treated control cells. Antioxidant tempol, a piperidine nitroxide considered a SOD mimetic, reversed BSO-induced decline in SOD activity (p < 0.01) and also increased BSO-induced decline in total antioxidant capacity (p < 0.05). Interestingly, BSO treatment significantly reduced mitochondrial oxygen consumption (p < 0.05), decreased mitochondrial membrane potential (p < 0.05), and lowered ATP production (p < 0.05) when compared to vehicle treated control cells, collectively indicative of mitochondrial impairment.