R.; Lober, S.; Hubner, H.; Gmeiner, P., Click chemistry on solid phase: parallel synthesis of -benzyltriazole carboxamides as super-potent G-protein coupled receptor ligands.
Organic chemistry: “Amino acid and polypeptide synthesis”. Amino acid synthesis--Gabriel synthesis; synthesis. degradation. Polypeptide synthesis-- () and () amino-protecting groups; protection of the terminus via ester formation; DCC () -activating reagent. An example of calculating and charge at a specific pH for a long polypeptide
Organic chemistry: “Alcohols, oxidation, and reduction”. Oxidation of alcohols (PCC). Reduction of and with to form alcohols. Synthesis with . Reduction of with NaBH4 or LiAlH4 to form alcohols.
Organic chemistry: “”. How to make and alkyl (). Reactions of and alkyl (with solvents, and , and ). Synthesis problems—using radical , E2, SN2, oxidation (PCC), and for synthesis. The “” technique for solving synthesis problems.
Organic chemistry: “Introduction to Grignard reagents”. Reaction of Grignard reagents as bases with solvents. Reaction of as with and . Introduction to synthesis with .
Organic chemistry: “ aromatic substitution”. aromatic substitution of benzene. Substitution through intermediates. Summary of methods for synthesis of phenols. oxidation to carboxylic acids; synthesis problems involving oxidation. Radical
Organic chemistry: “ of alkenes”. addition reactions. Addition of OsO4 (osmium ) to achieve . Using to achieve anti . A synthesis problem. The synthetic toolbox. When does hindrance block one face of a planar intermediate?
Organic chemistry: “Ethers”. Ethers. Williamson ether synthesis (preparation of ethers via SN2); . Digression on how to remember the -Lowry and Lewis definitions of acids and bases. Cleavage of ethers with (HX). Effect of positive formal charges on reactivity. Effect of acid or base on reactivity.
Organic chemistry: “ synthesis and reactions”. of carbons; acidity of alkynes; use of anions as for SN2 reactions and for attack on (). synthesis from by double elimination; synthesis from alkenes by -double . reactions. Hydrogenation of alkynes; hydrogenation of with catalyst to form alkenes; sequential one-electron reduction of alkynes with sodium metal to form trans alkenes. addition of HX to alkynes; addition of X2 to alkynes (). ; ; mercuric ion-catalyzed hydration of alkynes to form
Organic chemistry: “”. of alcohols (PBr3, SOCl2). (, alkyl , ). Using the technique to solve synthesis problems involving (Gilman reagents).
With its origins from a casual hallway conversation between Profs. Roger Acey and Kensaku Nakayama some years ago, these two began a collaboration focused on examining the development of inhibitors that targeted butyrylcholinesterase (BChE) at a time when researchers were largely focused on inhibiting acetylcholinesterase (AChE) to treat cognitive loss among patients suffering from Alzheimer's disease (AD). Profs. Acey & Nakayama soon realized that simple structural modifications to organophosphorus inhibitors could greatly enhance the selectivity of BChE inhibition over that of AChE. These early observations encouraged their collaboration to search for more effective organophosphorus inhibitors, leading to their initial collaborative publication in 2007.
Soon thereafter, Prof. Eric Sorin was enlisted to complement the synthetic and biochemical methods being employed with computer-based modeling and, more recently, this collaboration expanded to include Prof. Jason Schwans. The Nakayama, Schwans, and Sorin labs recently published their first collaborative article, , in (2017, , 3171-3181), illustrating the sensitivity of inhibitor activity to chemical modification and providing a structural basis for the striking changes in inhibitor potency. The article was co-authored by five CNSM undergraduate and graduate students.
These observations serve as the basis for additional families of derivatives now under investigation, as well as motivating much more time-consuming and computationally intensive studies to better understand the dynamic nature of the BChE-inhibitor complex. In addition, Professor Kevin Sinchak is contributing his expertise via animal studies to evaluate the potential of previous and future compounds of investigation to treat AD-related cognitive loss. This multi-pronged approach represents a fruitful integration of subfields within our Department aimed at the singular goal of identifying new compounds for potential use in mitigating neurodegenerative diseases.
Organic chemistry: “Carboxylic acids and acid derivatives”. Acidity of carboxylic acids; ranking compounds in order of acidity. How to synthesize carboxylic acids: oxidation; carbonation; hydrolysis. The types of carboxylic acid derivative. The general pattern for attack on carboxylic acids and acid derivatives (addition-elimination). . Ranking carboxylic acids derivatives in order of reactivity
All members of our lab will collaborate with other members of the Pharmacology, Drug Metabolism, and Clinical Pharmacology departments to pursue small molecule hits from high throughput screens, perform lead optimization studies to develop structure-activity-relationships (SAR) and ultimately deliver small molecules with acceptable properties to validate novel targets/mechanisms in vivo animal models of target diseases. The molecular targets of interest are kinases, GPCRs, ion channels, nuclear hormone receptors and protein-protein interactions, with an emphasis on allosteric modulation as opposed to classical agonism/antagonism. Therapeutic areas of interest span cancer, neuroscience (schizophrenia, anxiety, pain, sleep, Parkinson's disease) and endocrinology (diabetes, obesity). Students will be exposed to every phase of classical drug discovery. As Director of Medicinal Chemistry in the Vanderbilt Program in Drug Discovery and Director of the Vanderbillt Specialized Chemistry Center (MLPCN), training in my laboratory will be broad and involve organic synthesis, medicinal chemistry, pharmacology and drug metabolism. For many programs in the neuroscience area, students will have the opportunity to also develop radioligands for binding assay development and PET tracers for imaging studies.