Strategies for the Synthesis of Scaffolds Found in Natural Products PDF Download
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Author: Renato A. Bauer
Publisher:
ISBN:
Category :
Languages : en
Pages : 658
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Book Description
A major challenge to finding compounds that modulate protein function is the identification of chemical matter for screening. Although Nature provides excellent options for screening in the form of natural products, sufficient quantities can be difficult to obtain and characterize. Thus, chemical synthesis plays a lead role in providing molecules for screening, and chemists must ultimately decide what to synthesize based on the predicted value of the end products. We developed new synthetic strategies to access compounds for screening. In each case, natural products serve as an inspiration for the developed chemistry. First, a strategy was developed that provides access to scaffolds based on bioactive alkaloids and terpenoids. A key feature of this strategy is the use of transition metals to mediate the synthesis of multiple scaffolds from simple enynes and diynes. A t -butylsulfinamide group serves as a convenient tether to facilitate this chemistry. Principal component analysis (PCA) is used to analyze the relationship of our synthetic scaffolds to naturally occurring alkaloids and terpenoids. Then, a chemical reaction was studied that provides access to benzannulated medium rings inspired by natural products. In the developed reaction, three reagent classes (TsOH, Cu[BF 4 ] 2 , and Tf 2 0) were shown to polarize the carbonyl of a polycyclic cyclohexadienone and subsequently cause a cationic fragmentation reaction that generates an aromatic ring annulated to a medium ring. This process efficiently produces 7- to 11- membered rings while tolerating a variety of common functional groups. Work is presented on efforts to apply this reaction to the synthesis of two natural products, heliannuol A and puerol A.
Author: Renato A. Bauer
Publisher:
ISBN:
Category :
Languages : en
Pages : 658
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Book Description
A major challenge to finding compounds that modulate protein function is the identification of chemical matter for screening. Although Nature provides excellent options for screening in the form of natural products, sufficient quantities can be difficult to obtain and characterize. Thus, chemical synthesis plays a lead role in providing molecules for screening, and chemists must ultimately decide what to synthesize based on the predicted value of the end products. We developed new synthetic strategies to access compounds for screening. In each case, natural products serve as an inspiration for the developed chemistry. First, a strategy was developed that provides access to scaffolds based on bioactive alkaloids and terpenoids. A key feature of this strategy is the use of transition metals to mediate the synthesis of multiple scaffolds from simple enynes and diynes. A t -butylsulfinamide group serves as a convenient tether to facilitate this chemistry. Principal component analysis (PCA) is used to analyze the relationship of our synthetic scaffolds to naturally occurring alkaloids and terpenoids. Then, a chemical reaction was studied that provides access to benzannulated medium rings inspired by natural products. In the developed reaction, three reagent classes (TsOH, Cu[BF 4 ] 2 , and Tf 2 0) were shown to polarize the carbonyl of a polycyclic cyclohexadienone and subsequently cause a cationic fragmentation reaction that generates an aromatic ring annulated to a medium ring. This process efficiently produces 7- to 11- membered rings while tolerating a variety of common functional groups. Work is presented on efforts to apply this reaction to the synthesis of two natural products, heliannuol A and puerol A.
Author: Mohit Kumar
Publisher: Springer
ISBN: 9789819731107
Category : Science
Languages : en
Pages : 0
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Book Description
The book explains the use of natural products as scaffolds in tissue engineering. It presents an introduction to the concept of natural product-based scaffolds and explores various fabrication strategies for their synthesis. The book highlights the wide range of applications of these scaffolds in tissue engineering, including their use in tissue regeneration, wound healing, plastic surgery, and breast reconstruction. Specific natural products, such as gums (xanthan, gellan, arabic, guar, ghatti gum), chitosan, collagen are discussed in separate chapters. In addition, various application of natural product loaded PCL and PLA scaffolds have also been discussed. Each chapter focuses on the application of these natural product based scaffolds and explores their potential in tissue engineering. It also covers specific applications of these scaffolds in tissue regeneration, including angiogenesis, bone, skin, and nerve tissue regeneration. The book addresses important considerations regarding the toxicity and regulatory aspects of natural product-based scaffolds and explores the challenges associated with their implementation and emphasizes the need for safety and compliance in their use. Overall, the book provides a comprehensive overview of the field. It serves as a valuable resource for researchers, scientists, and professionals in the field of tissue engineering.
Author: Stefan Bräse
Publisher: Royal Society of Chemistry
ISBN: 1782620303
Category : Medical
Languages : en
Pages : 486
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Book Description
This book addresses the various classes of privileged scaffolds and covers the history of their discovery and use.
Author: Mohit Kumar
Publisher: Springer Nature
ISBN: 9819731119
Category :
Languages : en
Pages : 308
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Book Description
Author: Stefan Bräse
Publisher: Royal Society of Chemistry
ISBN: 1782622241
Category : Medical
Languages : en
Pages : 487
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Book Description
One strategy to expedite the discovery of new drugs, a process that is somewhat slow and serendipitous, is the identification and use of privileged scaffolds. This book covers the history of the discovery and use of privileged scaffolds and addresses the various classes of these important molecular fragments. The first of the benzodiazepines, a class of drugs that is powerful for treating anxiety, may not have been discovered had it not been for a chance experiment on the contents of a discarded flask found during a lab clean-up. Some years later, scientists discovered that benzodiazepine derivatives were also effective in treating other diseases. This class of molecules was the first to be described as privileged in the sense that it is especially effective at altering the course of disease. Other privileged molecular structures have since been discovered, and since these compounds are so effective at interacting with numerous classes of proteins, they may be an effective starting point to look for new drugs against the supposedly “undruggable” proteins. Following introductory chapters presenting an overview, a historical perspective and the theoretical background and findings, main chapters describe the structure of privileged structures in turn and discuss major drug classes associated with them and their syntheses. This book provides comprehensive coverage of the subject through chapters contributed by expert authors from both academia and industry and will be an excellent reference source for medicinal chemists of a range of disciplines and experiences.
Author: Sinan Gai
Publisher:
ISBN:
Category :
Languages : en
Pages : 496
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Book Description
The first chapter of this thesis provides an introduction to natural products and describes how they are a valuable source of bioactive compounds, which feature heavily in clinically used drugs. The recently reported bioactive natural product maoecrystal V was introduced followed by the chemistry of cyclopropanes, which were intended to be used in the synthesis of maoecrystal V.Synthetic strategies towards the synthesis of maoecrystal V were investigated in chapter 2. A retrosynthetic analysis of maoecrystal V was proposed, which featured a cyclopropane ring expansion. Using a model system, the key step, an intermolecular Diels-Alder cycloaddition was used to construct the [2.2.2]-bicyclooctane scaffold of maoecrystal V. Concurrently to this work, Baran and co-workers completed the synthesis of maoecrystal V and found that it possessed little to no bioactivity against a wide range of cancer cell lines.An introduction to spiroketals and the less common benzannulated spiroketals followed by the methodology to construct them are described in chapter 3. Based on some preliminary results from another study, attention was turned to utilising donor-acceptor cyclopropanes in the synthesis of benzannulated n,5-spiroketals (n = 6 or 5), which are found in numerous bioactive natural products.
Author: Jie Jack Li
Publisher: Springer Science & Business Media
ISBN: 3642340652
Category : Science
Languages : en
Pages : 292
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Book Description
'Total Synthesis of Natural Products' is written and edited by some of today's leaders in organic chemistry. Eleven chapters cover a range of natural products, from steroids to alkaloids. Each chapter contains an introduction to the natural product in question, descriptions of its biological and pharmacological properties and outlines of total synthesis procedures already carried out. Particular emphasis is placed on novel methodologies developed by the respective authors and their research groups. This text is ideal for graduate and advanced undergraduate students, as well as organic chemists in academia and industry.
Author: Angelos Dimitrios Peroulias
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
This note is part of Quality testing.
Author: Robert Bergstrand Susick
Publisher:
ISBN:
Category :
Languages : en
Pages : 333
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Book Description
This dissertation encompasses several studies pertaining to natural product total synthesis, reaction methodology development, and organic materials. Given that natural product structures inspire the development of new agrochemicals and pharmaceuticals, their syntheses remain a worthwhile pursuit in organic chemistry. Furthermore, the successful completion of a total synthesis endeavor can confirm proposed molecular structures and biological activities, in addition to serving as a testing ground for new synthetic methods. Similarly, organic materials impact many areas of humanity, including technology, health, and energy conversion. Therefore, developing new reaction methodologies is crucial for expanding the architectures, and thereby properties, of organic materials. Specifically, photocatalysts and organic light-emitting diodes (OLEDs) often rely on photophysical properties imparted by N-containing polycyclic aromatic hydrocarbon (PAH) ligands. As such, new methods that provide access to unique N-containing heterocyclic scaffolds are highly desirable. Chapter one offers a current perspective on the field of natural product total synthesis. Although historically viewed as a highly competitive field, several recent syntheses demonstrate a growing spirit of collaboration in total synthesis. By forming alliances with chemists in other fields, industries, or laboratories, total synthesis chemists have made many breakthroughs that would arguably not have been possible if working independently. Chapter two describes our laboratory's total syntheses of several bioactive akuammiline alkaloids, including strictamine, 2(S)-cathafoline, akuammiline, -akuammigine, and 10-demethoxyvincorine. Our strategic approach to the natural products focused on the use of a modern variant of a classic reaction, the Fischer indolization, to install several rings and the common quaternary center found in each target. This strategy allowed for the first total syntheses of akuammilines bearing a methanoquinolizidine core, as well as those that bear vicinal quaternary centers. In addition, rearrangements of the methanoquinolizidine core were developed that allowed us to access pyrrolidinoindoline-containing akuammilines. Chapter three describes synthetic studies of the reactive intermediates 2,3-pyridyne and 4,5-pyrimidyne. Heterocycles bearing one or more nitrogen atom are privileged motifs in natural products and pharmaceuticals. Therefore, methodologies that decorate such heterocycles are of great interest to the synthetic and biological communities. Arynes are highly reactive, transient species that can efficiently build multiple bonds in a single transformation, and our lab is particularly interested in accessing new, heterocyclic arynes to study their reactivity. This study demonstrates the synthetic utility of 2,3-pyridyne and the undesired reactivity of a 4,5-pyrimidyne precursor. Chapter four describes synthetic studies toward the development of new methods to manipulate polypyridyl organometallic scaffolds. Ruthenium- and iridium-based polypyridyl organometallic complexes have been known for nearly a century and have broadly impacted the scientific community, including the areas of catalysis, bioimaging, and energy conversion. Despite decades of study, methods to synthesize polypyridyl ligands are limited to relatively few transformations, particularly when extending -conjugation. We detail the use of arynes to extend the conjugation of polypyridyl ligands "on-the-complex," thereby overcoming traditional limitations in ligand synthesis. We also disclose the first generation and trapping of a ligand-bound aryne on an organometallic complex. Chapter five describes the synthesis of a novel -extended carbazole ligand for the study of structure-property relationships in two-coordinate metal complexes. Recently, linear two-coordinate metal complexes of the general structure donor-metal-acceptor have been identified as promising dopants for OLEDs. Both the donor and acceptor ligand play a crucial role in tuning the photophysical properties of these complexes. However, donor ligands with extended -conjugation have not been studied in this context. Our approach leverages heterocyclic arynes to synthesize -extended donor ligands in a modular fashion, which can also apply to other PAHs. Subsequent photophysical studies of -extended two-coordinate metal complexes identify a new dopant that displays up to 80% photoluminescence efficiency.
Author: Paul Barry Finn
Publisher:
ISBN:
Category :
Languages : en
Pages : 353
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Book Description
Screening small molecule libraries is a powerful method for identifying biologically active substances. Current compound libraries are typically comprised of a large number of structurally similar compounds designed around bioactive core structures of known molecules. While the number of tested compounds are increasing, there has been a decline in drug-discovery success due to only a small region of chemical space being represented in these compound libraries. In addition, newly discovered biological targets tend not to be modulated by currently known natural products and molecular scaffolds. Diversity-oriented synthesis (DOS) aims to construct structurally novel and diverse products in a highly efficient manner to generate small-molecule libraries with a high degree of structural diversity and function. There is a need for new organic methodologies to access these atypical molecular scaffolds. The work presented here utilizes photochemical and titanium-mediated methodologies to access novel molecular scaffolds in two distinct directions: 1) by utilizing [2+2] photocycloaddition of pyridone-enynes to access functionalized cyclobutanoids capable of further modification and 2) by developing a novel Bredt's rule-arrest Kulinkovich-de Meijere reaction to produce alkaloid building blocks with useful functionality. 2-Pyridones are known to undergo photo-initiated [2+2] and [4+4] cycloadditions with themselves and other conjugated -systems. These transformations provide rapid access to highly functionalized cyclobutanoid and cyclooctanoid derivatives capable of further manipulation to access both known and novel chemical space. Utilizing [2+2] photocycloaddition of pyridones conjugated with enyne partners we prepared polycyclic cyclobutanoids with excellent regio- and stereoselectivity. Further, these products were functionalized to give complex tetracyclic molecular scaffolds. The described approach to the 5-8-5 framework of the fusicoccane family features a key intramolecular [4+4] photocycloaddition of tethered pyridones. Intelligent design of the tether and proper choice of solvent affords rapid assembly of the polycyclic framework and sets the relative stereochemistry of five stereogenic centers. The strategy for construction of cyclooctanoid natural products is part of a long standing program to utilize the powerful photochemical properties of 2 pyridone. A novel approach for rapid access to a structurally diverse array of amino-ketone scaffolds employing a Kulinkovich-de Meijere reaction of inexpensive lactam-olefin building blocks has been developed. The formation of cyclopropylamines from alkenes and amides, the Kulinkovich-de Meijere reaction, involves two carbon-carbon bond-forming steps. Strategic use of a tricyclic intermediate can arrest the process if the second step requires formation of a bridgehead double bond. This intramolecular transformation results in formation of carbocyclic amino ketone building blocks. Further manipulation provides access to novel three-dimensional chemical space from these building blocks to produce a spectrum of fused bicyclic scaffolds in a divergent yet predictable manner. These products allow access to complex molecular space that can serve as a platform for medicinal and biochemical investigations.
