Ronald C.D. Breslow (1931-2017): A career in review.

Reviewed herein are key research accomplishments of Professor Ronald Charles D. Breslow (1931-2017) throughout his more than 60 year research career. These accomplishments span a wide range of topics, most notably physical organic chemistry, medicinal chemistry, and bioorganic chemistry. These topics are reviewed, as are topics of molecular electronics and origin of chirality, which combine to make up the bulk of this review. Also reviewed briefly are Breslow's contributions to the broader chemistry profession, including his work for the American Chemical Society and his work promoting gender equity. Throughout the article, efforts are made to put Breslow's accomplishments in the context of other work being done at the time, as well as to include subsequent iterations and elaborations of the research.

Structural principles of insulin formulation and analog design: A century of innovation.

BACKGROUND: The discovery of insulin in 1921 and its near-immediate clinical use initiated a century of innovation. Advances extended across a broad front, from the stabilization of animal insulin formulations to the frontiers of synthetic peptide chemistry, and in turn, from the advent of recombinant DNA manufacturing to structure-based protein analog design. In each case, a creative interplay was observed between pharmaceutical applications and then-emerging principles of protein science; indeed, translational objectives contributed to a growing molecular understanding of protein structure, aggregation and misfolding. SCOPE OF REVIEW: Pioneering crystallographic analyses-beginning with Hodgkin's solving of the 2-Zn insulin hexamer-elucidated general features of protein self-assembly, including zinc coordination and the allosteric transmission of conformational change. Crystallization of insulin was exploited both as a step in manufacturing and as a means of obtaining protracted action. Forty years ago, the confluence of recombinant human insulin with techniques for site-directed mutagenesis initiated the present era of insulin analogs. Variant or modified insulins were developed that exhibit improved prandial or basal pharmacokinetic (PK) properties. Encouraged by clinical trials demonstrating the long-term importance of glycemic control, regimens based on such analogs sought to resemble daily patterns of endogenous ß-cell secretion more closely, ideally with reduced risk of hypoglycemia. MAJOR CONCLUSIONS: Next-generation insulin analog design seeks to explore new frontiers, including glucose-responsive insulins, organ-selective analogs and biased agonists tailored to address yet-unmet clinical needs. In the coming decade, we envision ever more powerful scientific synergies at the interface of structural biology, molecular physiology and therapeutics.

Biosynthesis, total synthesis, and biological profiles of Ergot alkaloids.

While the use of ergot alkaloids in folk medicine has been practiced for millennia, systematic investigations on their therapeutic potential began about 100 years ago. Subsequently, Albert Hofmann's discovery of lysergic acid diethylamide (LSD) and its intense psychedelic properties garnered worldwide attention and prompted further studies of this compound class. As a result, several natural ergot alkaloids were discovered and unnatural analogs were synthesized, and some were used to treat an array of maladies, including Alzheimer's and Parkinson's disease. While LSD was never commercially approved, recent clinical studies have found it can be an innovative and effective treatment option for several psychiatric disorders. Ongoing biosynthetic and total synthetic investigations aim to understand the natural origins of ergot alkaloids, help develop facile means to produce these natural products and enable their continued use as medicinal chemistry lead structures. This review recounts major developments over the past 20 years in biosynthetic, total synthetic, and pharmaceutical studies. Many ergot alkaloid biosynthetic pathways have been elucidated, with some of them subsequently applied toward "green" syntheses. New chemical methodologies have fostered a fast and efficient access to the ergoline scaffold, prompting some groups to investigate biological properties of natural product-like ergot alkaloids. Limited pharmaceutical applications have yet to completely bypass the undesirable side effects of ergotism, suggesting further studies of this drug class are likely needed and will potentially harness major therapeutic significance.

50 Years European Federation for Medicinal Chemistry (EFMC) - The Ascent of Medicinal Chemistry in Europe.

A historical overview of key events that led, 50 years ago, to the foundation of the European Federation for Medicinal Chemistry (EFMC), and the impact this had on promoting and structuring medicinal chemistry as a discipline in Europe. EFMC, together with the growing number of newly established national medicinal chemistry societies or divisions, created the framework for networking and knowledge exchange. This includes organizing conferences, in particular its biennial 'International Symposium on Medicinal Chemistry (EFMC-ISMC)'. Several interesting trends can be identified from EFMC meetings, EFMC governing bodies, or the federation's recognition of scientific excellence, that highlight changes in the medicinal chemistry community over the last decades, related to affiliation, gender, young scientists, communication tools, and embracing scientific advances.

Memoirs of the First 50 Years of the European Federation for Medicinal Chemistry (EFMC).

These memoirs span the first fifty years of the European Federation for Medicinal Chemistry (EFMC). They are the personal observations and remembrance of Prof. Henk Timmerman, who witnessed how the EFMC developed since its inception in December 1969, and are published at the occasion of the 50th anniversary of the EFMC. They include, with permission from the EFMC, material that was previously published in EFMC newsletters. These texts are for the first time united and completed, to tell the history of an organization that has accompanied and shaped the development of medicinal chemistry in Europe. They also highlight, through facts and anecdotes, the role of the men and women who are the scientific leaders and drivers of this extended scientific community.

The founding and activities of the Pharmacy Division of the Vilnius Medical Society.

The Pharmacy Division of the Vilnius Medical Society was founded in 1819. It was the first and only pharmacy organization in Lithuania until the beginning of the 20th century. At the time of its founding, there were only three other pharmacy organizations in the Russian Empire: the Riga Chemical-Pharmaceutical Society (1803), the Mitau (now Jelgava) Pharmacy Society (1808) and the St. Petersburg Pharmacy Society (1818). The Division did much to improve the practice of pharmacy, enhance pharmaceutical knowledge and education, support and encourage pharmaceutical research, as well as provide a forum for discussion of all matters of interest and concern to the pharmacy profession. Through its publications, rich library and study collections, pharmacists in Vilnius and the Vilnius governorate stayed abreast of all the major developments and discoveries in the medical and pharmaceutical sciences. After the closing of Vilnius University in 1832 and of the Vilnius Medical-Surgical Academy in 1842, the Vilnius Medical Society, and hence its Pharmacy Division, lost its academic base. Pharmaceutical chemistry suffered especially. Pharmacists turned their attention to their practices and business interests. Their interest in the Society waned and their membership dwindled. In the beginning of the 20th century, especially after Lithuania regained its independence in 1918, other organizational opportunities opened up to them.

[Pharmaceutical chemist Tang Tenghan].

Tang Tenghan (1900-1988), who was a famous pharmaceutical chemist in China, was born in Java, Indonesia. He received his PhD from Institute of Pharmacy, Department of Philosophy in Berlin University. After returning to China, Tang Tenghan was employed by Shandong University, National Pei Yang University, West China Union University and Tongji University, etc. He engaged in education and scientific research in Pharmacy, Chemistry and Chemical Engineering. He was one of early scholars using pharmacognosy, chemistry and pharmacology on Chinese materia medica. At the same time, he held the concurrent position in pharmaceutical factory and took charge the production of drugs. After the founding of the People's Republic of China, he organized and led the anti-chemical agent research in Academy of Military Medical Sciences. In addition, Tang Tenghan contributed to the preparation of pharmacopoeia, the compilation of textbooks and the cultivation of talents. This paper made a detailed investigation of Tang Tenghan's lifework, analyzed the contribution and significance of his work in the history of Chemistry and Pharmacy, reflected the spirit of a generation of scientists.

Last Decade of Unconventional Methodologies for the Synthesis of Substituted Benzofurans.

This review describes the progress of the last decade on the synthesis of substituted benzofurans, which are useful scaffolds for the synthesis of numerous natural products and pharmaceuticals. In particular, new intramolecular and intermolecular C-C and/or C-O bond-forming processes, with transition-metal catalysis or metal-free are summarized. (1) Introduction. (2) Ring generation via intramolecular cyclization. (2.1) C7a-O bond formation: (route a). (2.2) O-C2 bond formation: (route b). (2.3) C2-C3 bond formation: (route c). (2.4) C3-C3a bond formation: (route d). (3) Ring generation via intermolecular cyclization. (3.1) C7a-O and C3-C3a bond formation (route a + d). (3.2) O-C2 and C2-C3 bond formation: (route b + c). (3.3) O-C2 and C3-C3a bond formation: (route b + d). (4) Benzannulation. (5) Conclusion.

Quo Vadis qNMR?

The quantification of a drug, its impurities, and e.g. components of a mixture has become routine in NMR laboratories and many applications have been described in the literature. However, besides simply using 1D 1H or 13C NMR, a number of more advanced methods has been developed and used in the past. Here, we want to describe the applicability of nuclei beyond the classical ones 1H and 13C. Mixtures can be characterized much better by applying various chemometric methods and separating the signals of mixture components can be achieved by DOSY experiments. All these methods contribute to the platform of qNMR methods and extend the possibilities of NMR for quantification and quality evaluation of drugs, excipients, polymers, and plant extracts. However, for quantification purposes, validation is always an issue and it is necessary to think about taking NMR related measures which might be different from the ones considered for chromatographic methods.

What is hidden in the biodiversity? The role of natural products and medicinal chemistry in the drug discovery process.

This manuscript describes the role of natural products in the process of drug discovery. In fact, several different natural compounds have been used as inspiration to develop new drugs. Some relevant examples are presented in chronological order.