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Theme Issue Honoring Professor Dr. Gordon W. Gribble on His Retirement

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Organic Chemistry".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 9450

Special Issue Editors


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Guest Editor
School of Sciences, Engineering, Art and Nursing, Eastern Mennonite University, Harrisonburg, VA, USA
Interests: heterocyclic chemistry; indoles and pyridines; water quality monitoring

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Guest Editor
Columbia University Irving Medical Center, New York, NY, USA
Interests: heterocyclic chemistry; medicinal chemistry; natural products; fragrance and flavor chemistry
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Special Issue Information

Dear Colleagues,

Gordon W. Gribble obtained his Ph.D. in Organic Chemistry at the University of Oregon in 1967. He was a National Institutes of Health Predoctoral Fellow in 1965–1967 and a National Cancer Institute Postdoctoral Fellow in 1967–1968 at The University of California, Los Angeles. In 1968, he joined the faculty of Dartmouth College, earned the title of Full Professor of Chemistry in 1980, and served as Chair from 1988 to 1991. He established his research group, which over the years has included as many as 46 graduate students, 33 postdoctoral researchers, and 152 undergraduates. Professor Gribble has been a Visiting Professor at numerous universities: the California Institute of Technology, the University of Waterloo, the General Electric Company, the University of Hawaii, the University of California at Santa Cruz, and Gettysburg College in Pennsylvania. 

Among his many accolades are a National Institutes of Health Research Career Development Award, 1971–1976, a National Science Foundation Science Faculty Professional Development Award, 1977–1978, Dartmouth Senior Faculty Fellowships in 1984, 1991, and 1999, the American Cyanamid Academic Award in 1988, and the Arts and Sciences Graduate Faculty Mentoring Award in 2006. In 2005, Professor Gribble was honored by being selected to hold the inaugural endowed “The Dartmouth Professor of Chemistry” Chair.

He is an active member of the American Chemical Society and the International Society of Heterocyclic Chemistry. Professor Gribble has an extensive publication and presentation record on topics that span both organic and environmental chemistry. His approximately 400 papers and review articles focus on the areas of chemical toxicology, naturally occurring organohalogens, the synthesis of biologically active natural products, new synthetic methodology, heterocyclic organic chemistry, novel DNA bis-Intercalators, and synthetic triterpenoids. One of these synthetic triterpenoids, “CDDO” (bardoxolone methyl), demonstrated significant anti-inflammatory activity and has been studied in Phase 3 clinical trials for the treatment of chronic kidney disease in diabetes patients. Professor Gribble has published four books, has co-edited the annual series “Progress in Heterocyclic Chemistry” since 1995 and has co-authored two editions of “Palladium in Heterocyclic Chemistry”, with Jack Li. 

This Special Issue of Molecules, in honor of Gordon W. Gribble, welcomes both manuscripts describing original work as well as review articles. The guest editors specifically invite submissions that focus on indole chemistry, including new methodologies toward the synthesis of indoles, synthetic approaches to novel indole-containing natural products, and studies on the reactivity and applications of novel indoles. Articles that are related to Professor Gribble’s other research interests may be considered as well.

Prof. Dr. Tara Kishbaugh
Dr. Alison Rinderspacher
Guest Editors

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Keywords

indole chemistry;

areas of chemical toxicology;

naturally occurring organohalogens;

the synthesis of biologically active natural products;

new synthetic methodology, heterocyclic organic chemistry;

novel DNA bis-Intercalators;

synthetic triterpenoids

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Published Papers (3 papers)

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Research

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11 pages, 2884 KiB  
Article
Stereoelectronic Features of a Complex Ketene Dimerization Reaction
by Robert D. Barrows, Mark J. Dresel, Thomas J. Emge, Paul R. Rablen and Spencer Knapp
Molecules 2022, 27(1), 66; https://doi.org/10.3390/molecules27010066 - 23 Dec 2021
Viewed by 3469
Abstract
The amidation reaction of a tetrahydroisoquinolin-1-one-4-carboxylic acid is a key step in the multi-kilogram-scale preparation of the antimalarial drug SJ733, now in phase 2 clinical trials. In the course of investigating THIQ carboxamidations, we found that propanephosphonic acid anhydride (T3P) is an effective [...] Read more.
The amidation reaction of a tetrahydroisoquinolin-1-one-4-carboxylic acid is a key step in the multi-kilogram-scale preparation of the antimalarial drug SJ733, now in phase 2 clinical trials. In the course of investigating THIQ carboxamidations, we found that propanephosphonic acid anhydride (T3P) is an effective reagent, although the yield and byproducts vary with the nature and quantity of the base. As a control, the T3P reaction of a 3-(2-thienyl) THIQ was performed in the absence of the amine, and the products were characterized: among them are three dimeric allenes and two dimeric lactones. A nucleophile-promoted ketene dimerization process subject to subtle steric and stereoelectronic effects accounts for their formation. Two novel monomeric products, a decarboxylated isoquinolone and a purple, fused aryl ketone, were also isolated, and mechanisms for their formation from the ketene intermediate are proposed. Full article
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13 pages, 2765 KiB  
Article
Natural Product Rottlerin Derivatives Targeting Quorum Sensing
by Dittu Suresh, Shekh Sabir, Tsz Tin Yu, Daniel Wenholz, Theerthankar Das, David StC. Black and Naresh Kumar
Molecules 2021, 26(12), 3745; https://doi.org/10.3390/molecules26123745 - 19 Jun 2021
Cited by 4 | Viewed by 2595
Abstract
Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were [...] Read more.
Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, 8b and 8d, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin. Full article
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Review

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10 pages, 3983 KiB  
Review
Improving the Cellular Selectivity of a Membrane-Disrupting Antimicrobial Agent by Monomer Control and by Taming
by Steven L. Regen
Molecules 2021, 26(2), 374; https://doi.org/10.3390/molecules26020374 - 13 Jan 2021
Cited by 2 | Viewed by 2013
Abstract
Antimicrobial resistance represents a significant world-wide health threat that is looming. To meet this challenge, new classes of antimicrobial agents and the redesign of existing ones will be required. This review summarizes some of the studies that have been carried out in my [...] Read more.
Antimicrobial resistance represents a significant world-wide health threat that is looming. To meet this challenge, new classes of antimicrobial agents and the redesign of existing ones will be required. This review summarizes some of the studies that have been carried out in my own laboratories involving membrane-disrupting agents. A major discovery that we made, using a Triton X-100 as a prototypical membrane-disrupting molecule and cholesterol-rich liposomes as model systems, was that membrane disruption can occur by two distinct processes, depending on the state of aggregation of the attacking agent. Specifically, we found that monomers induced leakage, while attack by aggregates resulted in a catastrophic rupture of the membrane. This discovery led us to design of a series of derivatives of the clinically important antifungal agent, Amphotericin B, where we demonstrated the feasibility of separating antifungal from hemolytic activity by decreasing the molecule’s tendency to aggregate, i.e., by controlling its monomer concentration. Using an entirely different approach (i.e., a “taming” strategy), we found that by covalently attaching one or more facial amphiphiles (“floats”) to Amphotericin B, its aggregate forms were much less active in lysing red blood cells while maintaining high antifungal activity. The possibility of applying such “monomer control” and “taming” strategies to other membrane-disrupting antimicrobial agents is briefly discussed. Full article
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