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Shengyin Zhao - One of the best experts on this subject based on the ideXlab platform.

Craig J Forsyth - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis of the C22–C40 Domain of the Azaspiracids
    2016
    Co-Authors: Zhigao Zhang, Yong Chen, Daniel Adu-ampratwum, Antony Akura Okumu, Nathaniel T. Kenton, Craig J Forsyth
    Abstract:

    An efficient synthesis of the C22–C40 domain of the azaspiracids is described. The synthetic route features a Nozaki–Hiyama–Kishi (NHK) coupling and chelation controlled Mukaiyama aldol reaction to access an acyclic intermediate and a double-intramolecular-Hetero-Michael Addition (DIHMA) to provide the FG-ring system bridged ketal

  • antibodies with broad specificity to azaspiracids by use of synthetic haptens
    Journal of the American Chemical Society, 2006
    Co-Authors: Craig J Forsyth, Son T Nguyen, Ingunn A Samdal, Lyn R Briggs, Thomas Rundberget, Morten Sandvik, Christopher O Miles
    Abstract:

    The development of general, sensitive, portable, and quantitative assays for the azaspiracid (AZA) class of marine toxins is urgently needed. Use of a synthetic hapten containing rings F-I of AZA to generate antibodies that cross-react with the AZAs via their common C28-C40 domain and use of these antibodies in ELISA and immunoaffinity columns are reported. This approach has many advantages over using intact azaspiracids (AZAs) derived from environmental samples or total synthesis as haptens for antibody development. A derivative of the levorotatory C28-C40 azaspiracid domain (1) was synthesized efficiently using a one-pot Staudinger reduction/intramolecular aza-Wittig reaction-imine capture sequence to form the H-I ring spiroaminal and a double intramolecluar Hetero-Michael Addition to assemble the F-G ring ketal. Conjugation of the hapten 1 to cBSA and immunization in sheep generated antibodies that recognized and bound to ovalbumin-conjugated 1 in the absence of AZA1. This binding was inhibited by 1 in a concentration-dependent manner. A mixture of AZA1, AZA2, AZA3, and AZA6 caused a degree of inhibition of antibody binding consistent with its total AZA content, rather than just its content of AZA1. This result suggests that the antibodies also have a similar affinity for AZA2, AZA3, and AZA6 as they do for AZA1 and that such antibodies are suitable for analysis of AZAs in shellfish samples.

  • application of the double intramolecular hetero michael Addition dihma approach in spiroketal synthesis total synthesis of 4s 6s 4 hydroxy 1 7 dioxaspiro 5 5 undecane a dacus oleae olive fly pheromone
    Tetrahedron Letters, 2002
    Co-Authors: Junliang Hao, Craig J Forsyth
    Abstract:

    Application of a novel double intramolecular Hetero-Michael Addition (DIHMA) strategy to spiroketal synthesis was illustrated by a concise synthesis of (±)-(4S*,6S*)-4-hydroxy-1,7-dioxaspiro[5.5]undecane, a Dacus oleae olive fly pheromone.

  • synthesis of a 2 9 dioxabicyclo 3 3 1 nonane via double intramolecular hetero michael Addition entry to the f g ring system of the azaspiracids
    Organic Letters, 2001
    Co-Authors: Josep Aiguade, Junliang Hao, Craig J Forsyth
    Abstract:

    An effective approach to form a 1,3-disubstituted 2,9-dioxabicyclo[3.3.1]nonane system representing the core of the F and G rings (C28−C34) of the azaspiracid natural products has been developed. The double intramolecular Hetero-Michael Addition (DIHMA) of a diol upon an ynone generated the bicyclic ketal in a highly diastereoselective fashion.

Yoshiji Takemoto - One of the best experts on this subject based on the ideXlab platform.

  • mechanistic insight into asymmetric hetero michael Addition of α β unsaturated carboxylic acids catalyzed by multifunctional thioureas
    Journal of the American Chemical Society, 2018
    Co-Authors: Noboru Hayama, Ryuta Kuramoto, Tamas Foldes, Kazuya Nishibayashi, Yusuke Kobayashi, Imre Papai, Yoshiji Takemoto
    Abstract:

    Carboxylic acids and their corresponding carboxylate anions are generally utilized as Bronsted acids/bases and oxygen nucleophiles in organic synthesis. However, a few asymmetric reactions have used carboxylic acids as electrophiles. Although chiral thioureas bearing both arylboronic acid and tertiary amine were found to promote the aza-Michael Addition of BnONH2 to α,β-unsaturated carboxylic acids with moderate to good enantioselectivities, the reaction mechanism remains to be clarified. Detailed investigation of the reaction using spectroscopic analysis and kinetic studies identified tetrahedral borate complexes, comprising two carboxylate anions, as reaction intermediates. We realized a dramatic improvement in product enantioselectivity with the Addition of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not only activates the carboxylate ligand as a Lewis acid, together with the thiourea NH-protons, but also functions as a Bronsted base through a benzoyloxy anion to activate th...

  • Mechanistic Insight into Asymmetric Hetero-Michael Addition of α,β-Unsaturated Carboxylic Acids Catalyzed by Multifunctional Thioureas
    2018
    Co-Authors: Noboru Hayama, Ryuta Kuramoto, Kazuya Nishibayashi, Yusuke Kobayashi, Tamás Földes, Imre Pápai, Yoshiji Takemoto
    Abstract:

    Carboxylic acids and their corresponding carboxylate anions are generally utilized as Brønsted acids/bases and oxygen nucleophiles in organic synthesis. However, a few asymmetric reactions have used carboxylic acids as electrophiles. Although chiral thioureas bearing both arylboronic acid and tertiary amine were found to promote the aza-Michael Addition of BnONH2 to α,β-unsaturated carboxylic acids with moderate to good enantioselectivities, the reaction mechanism remains to be clarified. Detailed investigation of the reaction using spectroscopic analysis and kinetic studies identified tetrahedral borate complexes, comprising two carboxylate anions, as reaction intermediates. We realized a dramatic improvement in product enantioselectivity with the Addition of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not only activates the carboxylate ligand as a Lewis acid, together with the thiourea NH-protons, but also functions as a Brønsted base through a benzoyloxy anion to activate the nucleophile. Moreover, molecular sieves were found to play an important role in generating the ternary borate complexes, which were crucial for obtaining high enantioselectivity as demonstrated by DFT calculations. We also designed a new thiourea catalyst for the intramolecular oxa-Michael Addition to suppress another catalytic pathway via a binary borate complex using steric hindrance between the catalyst and substrate. Finally, to demonstrate the synthetic versatility of both Hetero-Michael Additions, we used them to accomplish the asymmetric synthesis of key intermediates in pharmaceutically important molecules, including sitagliptin and α-tocopherol

  • a dual arylboronic acid aminothiourea catalytic system for the asymmetric intramolecular hetero michael reaction of α β unsaturated carboxylic acids
    ChemInform, 2015
    Co-Authors: Takumi Azuma, Yusuke Kobayashi, Akihiro Murata, Tsubasa Inokuma, Yoshiji Takemoto
    Abstract:

    For the first time aminoboronic acids (such as BNP) are used as efficient catalysts for the direct intramolecular Hetero-Michael Addition to α,β-unsaturated carboxylic acids to give a wide variety of O- and N-containing heterocycles.

Shengping Zheng - One of the best experts on this subject based on the ideXlab platform.

Yunxia Deng - One of the best experts on this subject based on the ideXlab platform.