37964-17-3Relevant articles and documents
Asymmetric Synthesis of a Bacteriochlorophyll Model Compound Containing trans-Dialkyl Substituents in Ring D
Nguyen, Khiem Chau,Wang, Pengzhi,Sommer, Roger D.,Lindsey, Jonathan S.
, p. 6605 - 6619 (2020)
Challenges to the de novo synthesis of bacteriochlorophyll a (BChl a), the chief pigment for anoxygenic bacterial photosynthesis, include creating the macrocycle along with the trans-dialkyl substituents in both pyrroline rings (B and D). A known route to a model bacteriochlorophyll with a gem-dimethyl group in each pyrroline ring has been probed for utility in the synthesis of BChl a by preparation of a hybrid macrocycle (BC-1), which contains a trans-dialkyl group in ring D and a gem-dimethyl group in ring B. Stereochemical definition began with the synthesis of (2S,3S)-2-ethyl-3-methylpent-4-ynoic acid, a precursor to the trans-dialkyl-substituted AD dihydrodipyrrin. Knoevenagel condensation of the latter and a gem-dimethyl, β-ketoester-substituted BC dihydrodipyrrin afforded the enone (E, 70%; Z, 3%); subsequent double-ring cyclization of the E-enone (via Nazarov, electrophilic aromatic substitution, and elimination reactions) gave BC-1 (53% yield) along with a trace of chlorin byproduct (1.4% relative to BC-1 upon fluorescence assay). BC-1 exhibited the desired trans-dialkyl stereochemistry in ring D and was obtained as a 7:1 mixture of (expected) epimers owing to the configuration of the 132-carbomethoxy substituent. The strategy wherein trans-dialkyl substituents are installed very early and carried through to completion, as validated herein, potentially opens a synthetic path to native photosynthetic pigments.
Palladium(II) Catalyzed C-H Functionalization Cascades for the Diastereoselective Synthesis of Polyheterocycles
Watt, Michael S.,Booker-Milburn, Kevin I.
supporting information, p. 5716 - 5719 (2016/11/17)
C-H activation offers huge potential in the generation of complex structures from simple starting materials. Herein we report the development of a highly diastereoselective palladium(II) catalyzed C-H functionalization cascade to produce novel, unsaturate
Identification of N-acylhydrazone derivatives as novel lactate dehydrogenase A inhibitors
Rupiani, Sebastiano,Buonfiglio, Rosa,Manerba, Marcella,Di Ianni, Lorenza,Vettraino, Marina,Giacomini, Elisa,Masetti, Matteo,Falchi, Federico,Di Stefano, Giuseppina,Roberti, Marinella,Recanatini, Maurizio
supporting information, p. 63 - 70 (2015/06/30)
Abstract Glycolysis is drastically increased in tumors and it is the main route to energy production with a minor use of oxidative phosphorylation. Among the key enzymes in the glycolytic process, LDH is emerging as one of the most interesting targets for the development of new inhibitors. In this context, in the present work, we carried out a virtual screening procedure followed by chemical modifications of the identified structures according to a "hit-to-lead" process. The effects of the new molecules were preliminary probed against purified human LDH-A. The compounds active at low micromolar level were additionally characterized for their activity on some cellular metabolic processes by using Raji human cell line. Within the series, 1 was considered the best candidate, and a more detailed characterization of its biological properties was performed. In Raji cells exposed to compound 1 we evidenced the occurrence of effects usually observed in cancer cells after LDH-A inhibition: reduced lactate production and NAD/NADH ratio, apoptosis. The flow cytometry analysis of treated cells also showed cell cycle changes compatible with effects exerted at the glycolytic level. Finally, in agreement with the data obtained with other inhibitors or by silencing LDH-A expression, compound 1 was found to increase Raji cells response to some commonly used chemotherapeutic agents. Taken together, all these finding are in support of the LDH-A inhibiting activity of compound 1.
