Author: Scott Twiddy
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Author: David James Skinner
Publisher:
ISBN:
Category :
Languages : en
Pages : 248

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Author: David Skinner
Publisher:
ISBN:
Category :
Languages : en
Pages :

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This thesis describes the efforts made towards the total synthesis of RP 66453, a highly strained macrocyclic tetrapeptide. RP 66453 provides an interesting synthetic challenge, not only due to its potential biological activity but also owing to its unusual chemical architecture. The strained bicyclic ring system features a 15-membered macrocycle containing an aryl-aryl bond and a 14-membered meta, para-cyclophane. Herein, several strategies towards the model A-B macrocycle of RP 66453 are presented featuring as a key step, a radical induced transannular ring contraction of a benzyl haloaryl ether and a photochemical transannular cyclisation of cis-stilbene derivatives. Synthetic efforts towards the B-O-C macrocycle are also presented, including copper-mediated and intramolecular SNAr cyclisation strategies. Finally, research into the union of these two fragments is presented followed by a discussion of a proposed end-game strategy.

Author: Lana Nanson
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Paul John Krenitsky
Publisher:
ISBN:
Category : Dopamine
Languages : en
Pages : 266

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Book Description
Neurotensin (NT) is a linear tridecapeptide first isolated from bovine hypothalamus shown to have pharmacological properties similar to dopamine antagonists, and as such, analogs of NT may be useful in the treatment of schizophrenia, psychoses, or depression. In the course of a screening program to identify compounds that displace NT from its receptor, RP 66453 was isolated and partially characterized. The connectivity structure was determined through spectroscopic methods and published in 1998, however the relative and absolute stereochemistry remain unsolved. RP 66453 was found to possess a unique and highly strained bicyclic ring system consisting of a 15-membered (AB) ring containing an endo aryl-aryl bond and a 14-membered (BC) ring containing a diaryl ether. This highly strained bicyclic tetrapeptide has never before been prepared synthetically. The S,S -isomer of a fully functionalized BC ring system of RP 66453, which constitutes an unusual reversed 14-membered cycloisodityrosine, was assembled through use of a key diaryl ether macrocyclization reaction enlisting a phenoxide nucleophilic aromatic substitution reaction of an o -fluoro nitroaromatic. The desired stereochemistry was maintained during the course of this synthesis, so it was expected that the conditions used for the cyclization reaction and removal of the nitro group would be suitable to apply to the synthesis of RP 66453. An appropriately functionalized derivative of the (S,S,S )-diastereomer of the 15-membered AB ring system of RP 66453 has been prepared by an unusually effective Suzuki coupling to form the aryl-aryl bond followed by macrolactamization. An optimal site of macrolactamization was identified, and the conformational and atropisomers issues associated with this unusual ring system were established. Two different routes were developed for the synthesis of the unique and highly strained bicyclic ring system of RP 66453. The first route employed diaryl ether formation for the final ring closure reaction, and the second route accomplished the final ring closure through macrolactamization. While not establishing the stereochemistry of RP 66453, these syntheses confirmed the structure of the carbon skeleton of the natural product and confirmed that the natural product does not possess the P,S,S,S,S -configuration.

Author: Miguel A. Sierra
Publisher: John Wiley & Sons
ISBN: 352765464X
Category : Science
Languages : en
Pages : 297

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Book Description
Success comes in many forms and in synthesis it can be a failure that results in their ultimate successful solutions. This long-awaited sequel to "Dead Ends and Detours" retains the proven concept while featuring over 20 new case studies of failed strategies and their (successful) solutions in natural product total synthesis. Additionally, computational models are used to discuss the problem in much more detail and to provide readers with additional information not found in the primary literature. The topics range from classic synthetic reactions (e.g. Diels Alder reaction), metal-mediated coupling reactions, metathesis, and asymmetric catalysis to the importance of protecting and activating groups. This book will benefit not only graduate students in organic chemistry but also advanced researchers as they gain knowledge derived from the step-by-step analysis of mistakes made in the past and, thus be able to improve their own chemical reaction planning. With its coverage of the most commonly applied reaction types, the book perfectly complements its predecessor, which focuses on general aspects, such as reactivity and selectivity.

Author: John ApSimon
Publisher: John Wiley & Sons
ISBN: 0470129506
Category : Science
Languages : en
Pages : 618

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Book Description
Each volume reviews the total synthesis of a set of compounds looking at syntheses reported historically and at the practice current at the time of publication. From volume 1 focusing on carbohydrates, prostagladins, nucleic acids, antibiotics, naturally occurring oxygen ring compounds and pyrrole pigments, the series continues with coverage of aromatic steroids, monoterpenes, triterpenes, sesquiterpenes, cannabinoids, natural inophores, insect pheromones and alkaloids. Volumes revisit the total synthesis of key compounds such as carbohydrates, nucleic acids and pyrrole pigments several times during the series building a picture of the historic development of total synthesis techniques for these major groups. Chapters are edited by experts in their field to give a complete overview of the best in the field at the time.

Author: John ApSimon
Publisher: John Wiley & Sons
ISBN: 0470129549
Category : Science
Languages : en
Pages : 562

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Book Description
Each volume reviews the total synthesis of a set of compounds looking at syntheses reported historically and at the practice current at the time of publication. From volume 1 focusing on carbohydrates, prostagladins, nucleic acids, antibiotics, naturally occurring oxygen ring compounds and pyrrole pigments, the series continues with coverage of aromatic steroids, monoterpenes, triterpenes, sesquiterpenes, cannabinoids, natural inophores, insect pheromones and alkaloids. Volumes revisit the total synthesis of key compounds such as carbohydrates, nucleic acids and pyrrole pigments several times during the series building a picture of the historic development of total synthesis techniques for these major groups. Chapters are edited by experts in their field to give a complete overview of the best in the field at the time.

Author: Ioannis D. Kostas
Publisher: MDPI
ISBN: 3038425567
Category : Science
Languages : en
Pages : 273

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Book Description
This book is a printed edition of the Special Issue "Suzuki–Miyaura Cross-Coupling Reaction and Potential Applications" that was published in Catalysts

Author: Eric Marsault
Publisher: John Wiley & Sons
ISBN: 1119092582
Category : Science
Languages : en
Pages : 653

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Book Description
Including case studies of macrocyclic marketed drugs and macrocycles in drug development, this book helps medicinal chemists deal with the synthetic and conceptual challenges of macrocycles in drug discovery efforts. Provides needed background to build a program in macrocycle drug discovery –design criteria, macrocycle profiles, applications, and limitations Features chapters contributed from leading international figures involved in macrocyclic drug discovery efforts Covers design criteria, typical profile of current macrocycles, applications, and limitations