The Asymmetric Organocatalytic Aza-Michael Addition: Efforts towards the Total Synthesis of Yuremamine and Development of New Domino Reactions PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download The Asymmetric Organocatalytic Aza-Michael Addition: Efforts towards the Total Synthesis of Yuremamine and Development of New Domino Reactions PDF full book. Access full book title The Asymmetric Organocatalytic Aza-Michael Addition: Efforts towards the Total Synthesis of Yuremamine and Development of New Domino Reactions by Céline Joie. Download full books in PDF and EPUB format.
Author: Céline Joie
Publisher:
ISBN: 9783843916844
Category :
Languages : de
Pages : 155
Get Book Here
Book Description
Author: Céline Joie
Publisher:
ISBN: 9783843916844
Category :
Languages : de
Pages : 155
Get Book Here
Book Description
Author: Haoran Xue
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Norzoanthamine is a complex heptacyclic marine alkaloid isolated from colonial zoanthids. It potently inhibits loss of bone weight and strength in a postmenopausal osteoporosis mouse model, but its mode-of-action remains unknown. The scarcity of this natural product from its natural source and the need to access analogs for structure-activity relationship (SAR) study make it necessary to chemically synthesize this compound. However, the complex molecular skeleton, especially the highly functionalized and stereochemically complex ABC core structure of the natural product poses a significant challenge. As part of our efforts to develop a practical synthetic route to norzoanthamine, we systematically explored a transannular Michael reaction cascade in the context of the synthesis of angular 6-6-6 tricyclic ring system, a mimic of the ABC core structure of norzoanthamine. Using 1,7-bis-enones in the form of 14-membered macrocyclic lactone as model substrates, we demonstrated that both E,Z- and E,E-macrocycles underwent facile transannular reactions to give cis-syn-cis and trans-anti-trans ring systems, respectively. However, Z,E- and Z,Z- macrocycles did not cyclize under similar reactions. The similarities and differences between transannular Diels-Alder reactions and this transannular cyclization process were also disclosed. Building upon these preliminary studies, we developed a 12-linear step synthesis of the ABC carbocyclic core of norzoanthamine. It features an organocatalytic asymmetric intramolecular aldolization to set the stereochemistry of the entire molecule, a fragment coupling based on selective alkylation of a bis-enolate, and a transannular Michael reaction cascade for rapid and stereoselective synthesis of the polycyclic core. Subsequent Claisen rearrangement enabled installation of a handle for introduction of the bottom piece to complete the total synthesis. Other efforts toward the total synthesis have also been discussed. The electronic version of this dissertation is accessible from http://hdl.handle.net/1969.1/149334
Author: Michael F. Greaney
Publisher: Elsevier Inc. Chapters
ISBN: 012805607X
Category : Science
Languages : en
Pages : 58
Get Book Here
Book Description
This chapter describes the synthesis of two related sesquiterpenes, anislactone A and merrilactone A. We initially accessed a tetracyclic oxetane in the merrilactone series using a Paternò–Büchi reaction but found the compound to be too underfunctionalized to advance further. We then developed an approach based on reductive epoxide ring opening, whereby a fully elaborated C-ring epoxy-cyclopentane, containing five stereocenters, could undergo reductive epoxide cleavage when treated with Ti(III). The resulting tertiary radical then participates in a 5-exo-dig cyclization onto a pendant alkyne to afford the complete carbon skeleton of both natural products. From this point, orthogonal functionalization routes enabled the synthesis of both anislactone A and merrilactone A. A second-generation merrilactone A synthesis is then described, growing out of discoveries made over the course of the first route in the area of cyclopentannulation. An iodo-aldol method was used to develop an approach to the anislactone skeleton and succeeded in producing the BC bicycle with good stereocontrol and functional group tolerance. Further functionalization, however, did not prove possible due to excessive steric hindrance around the incorporated iodo group preventing any productive transformation. This problem was solved by switching the nucleophile in the tandem-aldol process to cyanide. The resulting domino cyanide-addition aldol cyclization was then successfully employed in the formal synthesis of merrilactone A, using a late-stage [2+2] photocycloaddition to access the D-ring.
Author: Di Qiu
Publisher: World Scientific
ISBN: 1786348918
Category : Science
Languages : en
Pages : 533
Get Book Here
Book Description
Diazo compounds are versatile substances with diverse transformations in organic synthesis and other fields. Studies of diazo compounds have been ongoing for a very long time but still attract significant attention within the organic chemistry community, with new papers related to diazo compounds appearing at a daily pace. Over the past twenty years, there have been over fifty reviews and accounts related to the reactions of diazo compounds, but most of them cover limited aspects of diazo compounds. In addition to organic synthesis, diazo compounds have found applications in interdisciplinary fields such as material sciences, chemical biology and also polymerization.In this comprehensive book, the authors cover the most recent advances in the fields related to diazo compounds, including the application of donor-acceptor carbenes, carbene-based cross-coupling reactions and polymerizations, as well as the breakthrough in catalytic asymmetric carbene O-H, S-H, and N-H bond insertions. They also cover the application of flow chemistry in diazo reactions. The authors aim to provide a contemporary and comprehensive review for investigators engaged in or with interest in diazo compounds to boost further developments in this fascinating field.
![Synthetic Studies Toward the Total Synthesis (±)-ajmaline and the Development Of, Investigation Into, and Application of a Phosphine-catalyzed [4+1] Annulation PDF](https://books.google.com/books/content/images/frontcover/ULSjAQAACAAJ?fife=w80-h100)
Author: Brian Richard Blank
Publisher:
ISBN:
Category :
Languages : en
Pages : 325
Get Book Here
Book Description
Several synthetic routes toward the synthesis of the indole alkaloid (±)-ajmaline have been explored. The retrosynthetic plan was devised around two key transformations, one being a tandem aza-Michael-Michael reaction, and the other a phosphine-catalyzed [4+2] annulation. While these approaches have not allowed for the completion of ajmaline, they have provided a great deal of insight into the chemistry of many intermediates. For example, it was discovered that following installation of the D-ring, functionalization of the tricyclic scaffold to deliver a precursor for the aza-Michael-Michael sequence was a futile undertaking. As such, the necessary functionality had to be installed prior to the [4+2] annulation. For this purpose, ethyl 3-allyl-1H-indole-2-carboxylate was prepared by way of a stepwise Japp-Klingemann reaction, and a subsequent Fischer indolization. Successful conversion of this compound into the N-sulfonyl imine required the employment of 2,6-lutidine to impede isomerization of the allyl moiety. This imine was converted into the tetrahydropyridine through a phosphine-catalyzed [4+2] annulation with ethyl 2-methyl-2,3-butadienoate. Cross-metathesis with methyl acrylate provided the first precursor to the desired aza-Michael-Michael reaction sequence. Unfortunately, only mono-Michael addition was observed when this substrate was employed in the reaction, providing a tetracyclic structure instead of the desired pentacyclic scaffold. As a result, we are currently pursuing tricyclic derivatives that feature either alternative Michael donors or an increased strength of the second Michael acceptor. A phosphine-catalyzed [4+1] annulative rearrangement has been developed to prepare 3-pyrrolines from allenylic carbamates through phosphonium diene intermediates. This methodology was employed to synthesize an array of 1,3-disubstituted- and 1,2,3-trisubstituted-3-pyrrolines, including the often difficult to prepare 2-alkyl variants. A mechanistic investigation employing allenylic acetates and mononucleophiles unexpectedly unveiled that a phosphine-catalyzed [4+1] reaction previously reported by Tong might not occur through a phosphonium diene as was proposed, but rather involves multiple mechanisms working in concert to construct cyclopentene products. Consequentially, our phosphine-catalyzed rearrangement is most likely the first reaction that unequivocally forms a phosphonium diene intermediate along the reaction pathway. Concise formal syntheses of pyrrolizidine alkaloids (±)-trachelanthamidine and (±)-supinidine were completed, demonstrating the synthetic utility of this newly developed reaction.
Author: David J Procter
Publisher: Royal Society of Chemistry
ISBN: 184973075X
Category : Science
Languages : en
Pages : 221
Get Book Here
Book Description
Samarium diiodide is one of the most important reducing agents available to synthetic organic chemists. The lanthanide(II) reagent acts by single-electron transfer to organic substrates leading to the formation of both radical and/or anionic intermediates. The power of the reagent arises from its versatility - samarium diiodide can be used in processes ranging from functional group conversions to elaborate carbon-carbon bond-forming cyclization sequences that result in a dramatic increase in molecular complexity. In addition, reactions involving samarium diiodide often show high stereoselectivity as samarium ions can coordinate to Lewis basic sites on substrates and can direct the stereochemical course of reactions. The ability to fine-tune the reactivity of the reagent by the use of additives and co-solvents is an additional, attractive feature. Although samarium diiodide is used extensively by organic chemists, there is still a widely held view that the reagent can be difficult to prepare and use. In addition, samarium diiodide can mediate such a wide variety of organic chemistry that potential new users are often overawed by the extensive primary literature on the reagent. The objective of this book is to provide a concise, practical guide to the reagent. Rather than being a comprehensive review of the chemistry of samarium diiodide, this user-friendly book adopts an "an all you need to know" approach to the topic. The international authors are well-known for their work with the reagent and their expertise covers current developments in new reactivity and selectivity, applications in target synthesis, co-solvent and additive effects, coordination chemistry and mechanism. The book includes the best methods for preparing and handling the reagent, how solvents, co-solvents and additives alter reactivity, the basic mechanisms of reactions, common transformations using the reagent, and emerging areas in samarium diiodide chemistry. The authors have distilled the extensive primary literature to allow the reader to quickly grasp an understanding of the reagent and its utility. The illustrative practical procedures help the reader to prepare and use the reagent in the laboratory while references from the recent literature allow readers to pursue their interest in the popular reagent. The book also contains many illustrations and chemical schemes.
Author: Maksim Osipov
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
This dissertation deals with the development of metal-catalyzed asymmetric allylic alklyations, and their use for the synthesis of alkaloids and other nitrogen-containing biologically active compounds. The synthesis of the drug ( -- )-ranirestat is disclosed, which relies on a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) as a key step. The development and application of pyrroles and indoles as nucleophiles in the Pd-AAA is described. A Pd-catalyzed decarboxylative asymmetric alkylation approach to constructing vicinal all-carbon quaternary stereocenters is disclosed, and this methodology is used to complete the formal synthesis of several cyclotryptamine alkaloids. Finally, a catalytic asymmetric total synthesis of the alkaloid ( -- )-perophoramidine and efforts towards the alkaloid communesin B are described. Both syntheses employ a molybdenum-catalyzed asymmetric allylic alkylation as a key asymmetric step. ( -- )-Ranirestat is a potent aldose reductase inhibitor currently in phase III clinical testing for its ability to treat diabetic neuropathy. We have developed a concise, catalytic asymmetric total synthesis of ( -- )-ranirestat, which was completed in 8 steps and 14% overall yield starting from inexpensive, commercially available 2-(trichloroacetyl)pyrrole. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of an imidomalonate and an allylic carbonate serve as a key transformation to construct the tetrasubstituted stereocenter in the target with high yield and enantioselectivity. Protiodesilylation followed by oxidative cleavage of the allyl moiety and cyclization are used to access ( -- )-ranirestat. Nitrogen heterocycles are found in a variety of natural products and other biologically active compounds. We have demonstrated that pyrroles and indoles bearing electron-withdrawing groups are competent nucleophiles in the Pd-AAA with vinyl aziridines. The resulting alkylated products were obtained with high levels of regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this asymmetric process was demonstrated through the elaboration of pyrrole products into bromopyrrole alkaloids longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin. Likewise, the synthetic utility of the indole products was demonstrated by elaboration into several patented piperazinones and piperazine medicinal chemistry lead compounds. 1H-Pyrroles have also shown to serve as nucleophiles with meso electrophiles in the Pd-AAA. The products from this transformation were obtained as a single regio- and diastereomer in high yield and % ee. To demonstrate synthetic utility, a pyrrole-substituted nucleoside analogue was synthesized employing this methodology as the asymmetric step. Quaternary all-carbon stereocenters are present in many natural products and biologically active compounds. The presence of this structural element greatly complicates the asymmetric assembly of molecules due to steric congestion. The asymmetric assembly is complicated further when a second vicinal, quaternary center is present in a molecular target. We have discovered that a two-fold Pd-DAAA of an oxindole-derived dienol carbonate can be used to construct two vicinal all carbon quaternary stereocenters in a diastereo- and enantioselective fashion. To demonstrate the synthetic utility of this process, the product of this transformation was used to complete the formal syntheses of the cyclotryptamine alkaloids ( -- )-chimonanthine, (+)-calycanthine ( -- )-folicanthine, and ditryptophenaline. Mechanistic investigations have suggested that the two-fold Pd-catalyzed transformation proceeds through an unusual matched and mismatched allylation to deliver the desired product. Perophoramidine was isolated from the ascidian organism Perophora namei and displays cytotoxicity toward the HCT116 colon carcinoma cell line with an IC50 of 60 æM. The complex polycyclic cage-like core of this alkaloid makes it a challenging and interesting target for total synthesis. A catalytic asymmetric total synthesis of ( -- )-perophoramidine was developed employing a molybdenum-catalyzed asymmetric allylic alkylation between an allylic phosphate and an alkyl oxindole as an asymmetric step. This key transformation provides a chiral oxindole product in high yield and with high levels of regio-, diastereo-, and enantioselectivity. The chiral oxindole product, which contains the key quaternary stereocenter present in perophoramidine, was further elaborated to a pentacyclic imino ether using a reductive cyclization, oxidative cleavage and lactamization as key transformations. The imino ether was alkylated with allyl iodide to construct the second vicinal quaternary stereocenter providing an allyl imino ether as a single regio- and diastereomer. The allyl imino ether was converted to an aldehyde via ozonolysis, which was subjected to a reductive amination and cyclization sequence to complete ( -- )-perophoramidine.
Author: Y. Villacampa
Publisher: WIT Press
ISBN: 1784663093
Category : Mathematics
Languages : en
Pages : 243
Get Book Here
Book Description
Comprising specially selected papers on the subject of Computational Methods and Experimental Measurements, this book includes research from scientists, researchers and specialists who perform experiments, develop computer codes and carry out measurements on prototypes. Improvements relating to computational methods have generated an ever-increasing expansion of computational simulations that permeate all fields of science and technology. Validating the results of these improvements can be achieved by carrying out committed and accurate experiments, which have undertaken continuous development. Current experimental techniques have become more complex and sophisticated so that they require the intensive use of computers, both for running experiments as well as acquiring and processing the resulting data. This title explores new experimental and computational methods and covers various topics such as: Computer-aided Models; Image Analysis Applications; Noise Filtration of Shockwave Propagation; Finite Element Simulations.
Author: Paul T. Anastas
Publisher: Oxford University Press, USA
ISBN:
Category : Business & Economics
Languages : en
Pages : 392
Get Book Here
Book Description
The history of environmental protection has dealt with hazardous substances by cleaning them up or treating them after the substances have formed. Green Chemistry, however, designs products and processes so that no hazardous materials are used or made in the first place. With applications fromplastic to paints, from automobiles to pharmaceuticals, Green Chemistry is revolutionising science and industry and its impact on the environment.
Author: Henry Feuer
Publisher: John Wiley & Sons
ISBN: 9780470191545
Category : Science
Languages : en
Pages : 768
Get Book Here
Book Description
A comprehensive systematization of current novel data in nitrile oxide chemistry, this book authoritatively covers systematic strategies currently used in the preparation and utilization of nitrile oxides, nitrones, and nitronates in organic synthesis. It covers factors governing their stability and includes in-depth information on stable and unstable nitrile oxides. With contributions from leading experts, this is a definitive reference for practicing professionals in organic or medicinal chemistry and an excellent text for students studying organic synthesis.
