Download or read book Part I Total Synthesis of Azaspiracid 3 written by Eriketi Loizidou and published by . This book was released on 2006 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Toward Total Synthesis of Azaspiracid 3 and Azaspiracid 34 written by Antony Akura Okumu and published by . This book was released on 2016 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt: Azaspiracids are a class of marine natural products that accumulate in shellfish. Azaspiracid 1 was first reported in 1995 in the Netherlands after a poisoning incident and this led to its isolation and structure elucidation in 1998. Biological activities of azaspiracids are not fully known and further studies are necessary. They occur in scarce quantities in nature and therefore synthesis in the laboratory would facilitate these studies. There is need to examine their molecular pharmacology and to develop better means of their detection. The C1-C21 (ABCD) and C22-C40 (FGHI) fragments have been synthesized in our lab. The key reactions toward these synthesis were Nozaki-Hiyama-Kishi reaction, the Chelation controlled Mukaiyama aldol reaction, and trioxadispiroketalization under thermodynamic conditions. Earlier work in the group also involved gold-catalyzed trioxadispiroketalization. Syntheses of analogs of azaspiracids are necessary for toxicological studies, and to enable better environmental regulation. The highlight of the synthesis of the ABCD fragment of azaspiracid 34 was a Wittig olefination, selective conjugate reduction that was carried out at different stages of synthesis, and NHK coupling.

Download or read book Total Synthesis of Azaspiracid 3 C20 epi azaspiracid 3 and Structural Definition of the Azaspiracids written by Nathaniel T. Kenton and published by . This book was released on 2018 with total page 179 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the work described here, the previously-accepted structure of azaspiracid-3 was synthesized for the first time and shown to be non-identical to the natural product. A series of experiments, culminating in a total synthesis of the true structure, identified the C20 stereochemistry of the natural product as being epimeric to the expected structure. Because 1H-NMR data for the C19 and C20 methine protons among all known azaspiracids are very similar, a general stereochemical correction at C20 for this family of molecules is necessary. 5.5 mg of purified, natural azaspiracid-3 was produced.

Download or read book Towards the Total Synthesis of Azaspiracid 3 written by Ding Yue and published by . This book was released on 2010 with total page 127 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: A novel tert-butyl lithium mediated ring closure strategy was described in the synthesis of the carbon skeleton of azaspiracid-3. This novel strategy disconnected the compound into two fragments. The synthesis of both fragments was described. Because of reactivity issues, some protecting group must be altered before the coupling could be achieved. After coupling, the key ring closure proceeded as expected. Some purification techniques were needed in order to achieve the total synthesis of azaspiracid-3.

Download or read book Progress Towards the Total Synthesis of Azaspiracids written by Jianyan Xu and published by . This book was released on 2006 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Studies Toward the Total Synthesis of Azaspiracid 1 written by Brian Kenneth Raymer and published by . This book was released on 2004 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Effort Toward the Total Synthesis of Azaspiracid 3 written by Zhigao Zhang and published by . This book was released on 2013 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: A NHK reaction to couple the C1-C21 and C22-C40 domains has also been proposed. The revised C22-C40 domain was achieved with a similar synthetic route.

Download or read book Studies Toward the Total Synthesis of Azaspiracid 1 written by Damien L. Kuiper and published by . This book was released on 2010 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: Azaspiracid has generated an enormous amount of scientific interest in the fourteen years since its initial discovery. The structure contains a 6,5,6 bis-spiroketal, a [3.3.1] bicyclic ketal and a 6,5-spiroaminal linkage as key moieties. With 9 rings, 20 stereocenters and three alkenes, the azaspiracid immediately attracted the interest of the synthetic community. To date, two syntheses have been reported by the Nicolaou and Evans laboratories. An initial route to the C13-C19 aldehyde was plagued by a problematic 1,2 silyl migration. An improved route to the C13-C19 aldehyde was developed based on a modified protecting group strategy utilizing a PMP ketal. The improvements in the synthesis led to facile production of 250 mg of the key transoidal ABC ring bisspiroketal. This second generation route dramatically improved the efficiency of our synthesis, with the overall yield for the C13-C19 aldehyde increasing from 2% to 15%, which allowed the synthesis of over 250 mg the bisspiroketal. An optimized route to the FGHI spiroaminal was developed. A unique equilibration method for the construction of the anomerically-stabilized spiroaminal was discovered. After cleavage of the Cbz carbamate, an in situ tautomerization provided the desired doubly anomeric FGHI spiroaminal subunit. This transformed a total synthesis of FGHI spiroaminal into a process which could easily produce gram quantities of advanced intermediates requisite for the synthesis of azaspiracid. With an optimized synthesis of the FGHI ring system complete, a host of routes were investigated for the coupling of the C26-C40 fragment and C20-C25 fragment was developed. The C25-C26 bond was formed via an aldol condensation between FGHI methyl ester and the C20-C26 aldehyde. A novel TAS-F-mediated elimination was developed to provide the C26-C44 olefin. The Horner-Wadsworth-Emmons coupling of the C4-C19 lactol and C20-C40 ketophosphonate furnished the contiguous C4-C45 framework of azaspiracid-1. Davis oxidation of C20 provided the requisite oxidation state. The only challenges remaining are desilylation at C25 and cross metathesis at C4 to complete a formal synthesis of azaspiracid.

Download or read book Part I Total Sysnthesis of Azaspiracid 3 Part II Molecular Recognition Studies in Aqueous Solutions Facilitated by a Receptor Modified Polymer written by and published by . This book was released on 2006 with total page 364 pages. Available in PDF, EPUB and Kindle. Book excerpt: Part I. Azaspiracids are novel marine toxins produced by microalgae of the genus Protoperidinium . They were first identified in 1995 following an incident of food poisoning in the Netherlands. The major toxin azaspiracid-1 was isolated in 1998 and its structure was unambigously determined in 2004 after its first total synthesis by Nicolaou and others At least 11 analogues have been isolated and among them azaspiracid-1, -2 and -3 are the most potent toxins. Due to the difficulty of obtaining sufficient amount of toxin the studies towards their mechanism of action have been limited. The total synthesis of these toxins can provide sufficient material for biological studies as well as an opportunity to study structure activity relationships. Part I of this thesis reports the first total synthesis of azaspiracid-3. The synthetic strategy includes the same key reactions as those reported for the synthesis of azaspiracid-1; however, this synthetic route is shorter and more efficient. Part II. It is well established that therapeutic drugs are designed to bind substrates through various types of noncovalent interactions such as electrostatic, hydrogen bonding, [pi]-[pi] stacking and Van der Waals interactions. Hosts based on electrostatic, hydrophobic and [pi]-[pi] stacking interactions have been reported in the literature for potential applications in aqueous media to emulate functions in biological systems. However, to enable specific binding of hydrogen bonding based artificial receptors for aqueous solution applications such as in sensor and biomedicine technology, one must circumvent the competing effect of water. We introduce a general approach for applying hydrogen bonding based receptors in water, by covalently attaching a purely hydrogen bonding based barbiturate receptor to a water-soluble amphiphilic polymer. Amphiphilic polymers are known to self-associate in aqueous media forming micelle-like microdomains. The hydrophobic environment of the micelle allows hydrogen bonding based recognition to occur. The binding of barbiturates to the receptor-modified polymer is studied via UV spectroscopy and affinity capillary electrophoresis.

Download or read book Synthetic Studies on Total Synthesis of Azaspiracid 3 written by Yong Chen and published by . This book was released on 2013 with total page 216 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Azaspiracid, a structurally complex marine toxin isolated from the mussel Mytilus edulis in Killary Harbor, Ireland, represents a new class of marine toxin unrelated to any previous known agent of shellfish poisoning. Due to the interesting biological activities and challenging structures, these natural products have drawn considerable attention among organic chemists. This thesis details the study towards the total synthesis of azaspiracid-3.

Download or read book Classics in Total Synthesis III written by K. C. Nicolaou and published by John Wiley & Sons. This book was released on 2011-03-14 with total page 788 pages. Available in PDF, EPUB and Kindle. Book excerpt: K.C. Nicolaou - Winner of the Nemitsas Prize 2014 in Chemistry Adopting his didactically skillful approach, K.C. Nicolaou compiles in this textbook the important synthetic methods that lead to a complex molecule with valuable properties. He explains all the key steps of the synthetic pathway, highlighting the major developments in blue-boxed sections and contrasting these to other synthetic methods. A wonderful tool for learning and teaching and a must-have for all future and present organic and biochemists.

Download or read book Synthesis of the ABCD and EFGHI domains of Azaspiracid 3 written by Daniel Adu-Ampratwum and published by . This book was released on 2016 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Azaspiracids are a group of lipophilic polyether toxins that were recognized as being responsible for human poisoning in the Netherlands in 1995. These natural marine toxins have been isolated and characterized, from mussels of the species Mytilus edulis, by Yasumoto and co-workers, and later structurally revised by Nicolaou and co-workers. The structurally complex molecular architecture displayed by these natural products features a 40-carbon backbone containing 20 stereocenters and 9 rings which are made up of two distinct polyheterocyclic domains: a trioxadispiroketal fused onto a tetrahydrofuran (ABCD-domain) and a spirohemiaminal fused onto a 2,9-dioxabicyclo[3.3.1]nonane (FGHI-domain). These two domains are linked by a cyclic hemiketal designated as the E-ring. Due to the toxicity, complex architecture and the meager quantities obtained from natural sources (2 mg from 20 kg of mussels) as well as a growing need for authentic samples for environmental monitoring, the azaspiracids have stimulated considerable interest in the synthetic community. Nicolaou and co-workers reported the first synthesis of azaspiracid-1 in 2004 and a shorter synthesis of azaspiracid-1, -2, and -3 in 2006. The Evans group has also reported the synthesis of ent-azaspiracid-1. Several research groups have also reported their synthetic efforts towards these natural products. Our group has made considerable efforts in developing methods to construct the dioxabisspiroketal, the 2,9-dioxabicyclo[3.3.1]nonane and the spirohemiaminal subunits of azaspiracid-3. However a total synthesis of this natural product is yet to be achieved in our group and this is the primary aim of my research. As a second aim of my research, we are interested in contributing to environmental monitoring of these marine natural products. We hope to achieve this by designing an efficient synthetic route that can allow access to sufficient quantities of azaspiracid-3 and some natural analogs to aid in full biological assay.

Download or read book Part I written by Liang Lu and published by . This book was released on 2010 with total page 786 pages. Available in PDF, EPUB and Kindle. Book excerpt: The structural architecture present in marine toxin azaspiracid - 20 stereocenters, 9 rings, 3 separated spirocenters - has attracted considerable synthetic attention. Our efforts toward the synthesis of azaspiracid have led to the completion of both C1-C26 northern and C27-C40 southern halves. Herein, the synthesis of southern FGHI ring system is described. The key steps included an Andrus anti-aldol coupling to furnish the C32, C33 stereocenters, an acid-catalyzed ketalization to furnish FG rings, and a Yb(OTf)3-mediated spiroaminal formation to generate I ring. The first total synthesis of cytotoxic macrolides amphidinolide B1 and the proposed structure of amphidinolide B2 have been accomplished. The key developed protocols include a metal catalyst-free sequence for the synthesis of the diene subunit, a non-chelation-controlled aldol coupling to install the C18 stereocenter, an efficient macrocyclization of the 26-membered lactone ring, and the incorporation of the labile allylic epoxide moiety. The unique structure of the highly substituted diene functionality represents significant synthetic challenges. A Wittig / HWE reaction sequence yielded the C13-C15 diene moiety in good yield in excellent diastereoselectivity. Subsequent Sharpless epoxidation and Red-Al-mediated regionselective epoxide opening gave the C16 tertiary alcohol. The protecting groups on C21 were discovered to have significant effects on the aldol reaction between C9-C18 aldehyde and C19-C25 methyl ketone. Although chelating groups such as PMB, Bn afforded 18S isomer as a single diastereomer, the removal of these groups has proven problematic. Non-chelating silyl group generated 18R isomer in 8:1 dr at -100°C, while the 18S stereomer was obtained at -40°C in 1.2:1 dr. A spontaneous intramolecular Wadsworth-Emmons olefination established the 26-membered macrocycle. The oxidation and in situ elimination of a selenide moiety proceeded smoothly in the presence of free alcohols using TMSOOTMS. The first total synthesis of amphidinolide B1 and the proposed structure of amphidinolide B2 were accomplished in 29 linear steps. Additionally, We discovered that the initially proposed structure of amphidinolide B2 was incorrect.

Download or read book Synthesis of the C21 C40 Domain of Azaspiracid 3 written by Shuang Liang and published by . This book was released on 2007 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Synthesis of the ABCD Domain of the Azaspiracids written by Feng Zhou and published by . This book was released on 2010 with total page 139 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: This thesis describes synthetic efforts toward the total synthesis of the azaspiracid marine toxins. The investigation here focuses on the synthesis of the ABCD bis-spiroketal domain. Several different approaches have been developed. One features a gold catalyzed spiroketalization, which used a triple bond as an oxidation-state equivalent of a ketone to establish a spiroketal structure. In the D-ring synthesis, a Co(modp)2 (modp: 1-mophorlinocarbamoyl-4,4-dimethyl-1,3-pentadione) catalyzed oxyetherification was applied. In the recently revised synthetic route, the D-ring was constructed through a tandem asymmetric epoxidation and epoxide opening process.

Download or read book Synthesis of Spiroketal Domains of Marine Natural Products Part I Total Synthesis of 7 deoxy okadaic Acid and Analogues Part II Synthetic Investigations of the C1 C20 Domain of Azaspiracid written by Amy Beth Dounay and published by . This book was released on 2001 with total page 646 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Modern Methods in Stereoselective Aldol Reactions written by Rainer Mahrwald and published by John Wiley & Sons. This book was released on 2013-02-22 with total page 604 pages. Available in PDF, EPUB and Kindle. Book excerpt: The selective formation of bondings between molecules is one of the major challenges in organic chemistry, and the so-called aldol reaction is one of the most important for this purpose. These reactions are a highly useful tool for developing such novel substances as natural products and pharmaceuticals. Likes its highly successful and much appreciated predecessor, "Modern Aldol Reactions", this ready reference provides a systematic overview of methodologies for installing a required configuration during an aldol addition step, but shifts the focus so as to cover the latest developments. As such, it presents a set of brand new tools, including vinylogous Mukaiyama-aldol reactions and substrate-controlled aldol reactions, as well as asymmetric induction in aldol additions. Furthermore, new developments in existing stereoselective aldol additions are described, such as the deployment of supersilyl groups or organocatalyzed aldol additions. All of these methodologies are presented in the context of their deployment in the total synthesis of natural products.