The Experts below are selected from a list of 60 Experts worldwide ranked by ideXlab platform
Daniel Seidel - One of the best experts on this subject based on the ideXlab platform.
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Asymmetric Redox-Annulation of Cyclic Amines
2016Co-Authors: Youngku Kang, Weijie Chen, Martin Breugst, Daniel SeidelAbstract:ABSTRACT: Cyclic amines such as 1,2,3,4-tetrahydroisoqui-noline undergo regiodivergent annulation reactions with 4-nitrobutyraldehydes. These redox-neutral transformations enable the asymmetric synthesis of highly substituted polycyclic ring systems in just two steps from commercial materials. The utility of this process is illustrated in a rapid synthesis of (−)-protoemetinol. Computational studies provide mechanistic insights and implicate the elimination of acetic acid from an ammonium nitronate intermediate as the rate-determining step. Tryptoline (tetrahydro-β-carboline) and 1,2,3,4-tetrahydroiso-quinoline (THIQ) are substructures of numerous bioactive natural products that contain additional fused rings (Scheme 1).1 The desire to build such highly substituted polycycli
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intramolecular 3 2 cycloadditions of azomethine ylides derived from secondary amines via redox neutral c h functionalization
ChemInform, 2015Co-Authors: K Mantelingu, Yingfu Lin, Daniel SeidelAbstract:A vast number of secondary amines such as tetrahydroquinoline, Tryptoline, pyrrolidine, azepane, morpholine, dihydroindole, and dihydropyrrole derivatives are condensed with azomethine ylides deriving from aldehydes bearing a pendant dipolarophile.
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intramolecular 3 2 cycloadditions of azomethine ylides derived from secondary amines via redox neutral c h functionalization
Organic Letters, 2014Co-Authors: K Mantelingu, Yingfu Lin, Daniel SeidelAbstract:Azomethine ylides are accessed under mild conditions via benzoic acid catalyzed condensations of 1,2,3,4-tetrahydroisoquinolines or Tryptolines with aldehydes bearing a pendent dipolarophile. These intermediates undergo intramolecular [3 + 2]-cycloadditions in a highly diastereoselective fashion to form polycyclic amines with four new stereogenic centers. Challenging substrates such as piperidine, morpholine, and thiomorpholine undergo the corresponding reactions at elevated temperatures.
K Mantelingu - One of the best experts on this subject based on the ideXlab platform.
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intramolecular 3 2 cycloadditions of azomethine ylides derived from secondary amines via redox neutral c h functionalization
ChemInform, 2015Co-Authors: K Mantelingu, Yingfu Lin, Daniel SeidelAbstract:A vast number of secondary amines such as tetrahydroquinoline, Tryptoline, pyrrolidine, azepane, morpholine, dihydroindole, and dihydropyrrole derivatives are condensed with azomethine ylides deriving from aldehydes bearing a pendant dipolarophile.
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intramolecular 3 2 cycloadditions of azomethine ylides derived from secondary amines via redox neutral c h functionalization
Organic Letters, 2014Co-Authors: K Mantelingu, Yingfu Lin, Daniel SeidelAbstract:Azomethine ylides are accessed under mild conditions via benzoic acid catalyzed condensations of 1,2,3,4-tetrahydroisoquinolines or Tryptolines with aldehydes bearing a pendent dipolarophile. These intermediates undergo intramolecular [3 + 2]-cycloadditions in a highly diastereoselective fashion to form polycyclic amines with four new stereogenic centers. Challenging substrates such as piperidine, morpholine, and thiomorpholine undergo the corresponding reactions at elevated temperatures.
Xiaohong Liu - One of the best experts on this subject based on the ideXlab platform.
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solution phase dna compatible pictet spengler reaction aided by machine learning building block filtering
iScience, 2020Co-Authors: Xiaohong Liu, Sixiu Liu, Yanfang Shen, Qingxia Sun, Xiaodong Shi, Weiren Cui, Zhiqiang Duan, Letian Kuai, Hongfang YangAbstract:The application of machine learning toward DNA encoded library (DEL) technology is lacking despite obvious synergy between these two advancing technologies. Herein, a machine learning algorithm has been developed that predicts the conversion rate for the DNA-compatible reaction of a building block with a model DNA-conjugate. We exemplify the value of this technique with a challenging reaction, the Pictet-Spengler, where acidic conditions are normally required to achieve the desired cyclization between tryptophan and aldehydes to provide Tryptolines. This is the first demonstration of using a machine learning algorithm to cull potential building blocks prior to their purchase and testing for DNA-encoded library synthesis. Importantly, this allows for a challenging reaction, with an otherwise very low building block pass rate in the test reaction, to still be used in DEL synthesis. Furthermore, because our protocol is solution phase it is directly applicable to standard plate-based DEL synthesis.
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solution phase dna compatible pictet spengler reaction aided by machine learning building block filtering
2020Co-Authors: Xiaohong Liu, Sixiu Liu, Yanfang Shen, Qingxia Sun, Xiaodong Shi, Weiren Cui, Zhiqiang Duan, Letian Kuai, Hongfang Yang, Alexander L SatzAbstract:The application of machine learning towards DNA encoded library (DEL) technology is lacking despite obvious synergy between these two advancing technologies. Herein, a machine learning algorithm has been developed that predicts the conversion rate for the DNA compatible reaction of a building block with a model DNA-conjugate. We exemplify the value of this technique with a challenging reaction, the Pictet-Spengler, where acidic conditions are normally required to achieve the desired cyclization between tryptophan and aldehydes to provide Tryptolines. To avoid damaging the DNA our reaction conditions must be exceptionally mild, and therefore most building blocks fail to provide acceptable yields of desired product ( 78% pass rate. This is the first demonstration of using a machine learning algorithm to cull potential building blocks prior to their purchase and testing for DNA encoded library synthesis. Importantly, this allows for a challenging reaction, with an otherwise very low building block pass rate in the test reaction, to still be used in DEL synthesis. Furthermore, we discuss herein the rational design of DNA conjugated tryptophan substrates for our Pictet-Spengler reaction, and optimization of the reaction protocols. Lastly, because our protocol is solution-phase it is directly applicable to standard plate-based DEL synthesis.
Hongfang Yang - One of the best experts on this subject based on the ideXlab platform.
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solution phase dna compatible pictet spengler reaction aided by machine learning building block filtering
iScience, 2020Co-Authors: Xiaohong Liu, Sixiu Liu, Yanfang Shen, Qingxia Sun, Xiaodong Shi, Weiren Cui, Zhiqiang Duan, Letian Kuai, Hongfang YangAbstract:The application of machine learning toward DNA encoded library (DEL) technology is lacking despite obvious synergy between these two advancing technologies. Herein, a machine learning algorithm has been developed that predicts the conversion rate for the DNA-compatible reaction of a building block with a model DNA-conjugate. We exemplify the value of this technique with a challenging reaction, the Pictet-Spengler, where acidic conditions are normally required to achieve the desired cyclization between tryptophan and aldehydes to provide Tryptolines. This is the first demonstration of using a machine learning algorithm to cull potential building blocks prior to their purchase and testing for DNA-encoded library synthesis. Importantly, this allows for a challenging reaction, with an otherwise very low building block pass rate in the test reaction, to still be used in DEL synthesis. Furthermore, because our protocol is solution phase it is directly applicable to standard plate-based DEL synthesis.
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solution phase dna compatible pictet spengler reaction aided by machine learning building block filtering
2020Co-Authors: Xiaohong Liu, Sixiu Liu, Yanfang Shen, Qingxia Sun, Xiaodong Shi, Weiren Cui, Zhiqiang Duan, Letian Kuai, Hongfang Yang, Alexander L SatzAbstract:The application of machine learning towards DNA encoded library (DEL) technology is lacking despite obvious synergy between these two advancing technologies. Herein, a machine learning algorithm has been developed that predicts the conversion rate for the DNA compatible reaction of a building block with a model DNA-conjugate. We exemplify the value of this technique with a challenging reaction, the Pictet-Spengler, where acidic conditions are normally required to achieve the desired cyclization between tryptophan and aldehydes to provide Tryptolines. To avoid damaging the DNA our reaction conditions must be exceptionally mild, and therefore most building blocks fail to provide acceptable yields of desired product ( 78% pass rate. This is the first demonstration of using a machine learning algorithm to cull potential building blocks prior to their purchase and testing for DNA encoded library synthesis. Importantly, this allows for a challenging reaction, with an otherwise very low building block pass rate in the test reaction, to still be used in DEL synthesis. Furthermore, we discuss herein the rational design of DNA conjugated tryptophan substrates for our Pictet-Spengler reaction, and optimization of the reaction protocols. Lastly, because our protocol is solution-phase it is directly applicable to standard plate-based DEL synthesis.
Yingfu Lin - One of the best experts on this subject based on the ideXlab platform.
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intramolecular 3 2 cycloadditions of azomethine ylides derived from secondary amines via redox neutral c h functionalization
ChemInform, 2015Co-Authors: K Mantelingu, Yingfu Lin, Daniel SeidelAbstract:A vast number of secondary amines such as tetrahydroquinoline, Tryptoline, pyrrolidine, azepane, morpholine, dihydroindole, and dihydropyrrole derivatives are condensed with azomethine ylides deriving from aldehydes bearing a pendant dipolarophile.
-
intramolecular 3 2 cycloadditions of azomethine ylides derived from secondary amines via redox neutral c h functionalization
Organic Letters, 2014Co-Authors: K Mantelingu, Yingfu Lin, Daniel SeidelAbstract:Azomethine ylides are accessed under mild conditions via benzoic acid catalyzed condensations of 1,2,3,4-tetrahydroisoquinolines or Tryptolines with aldehydes bearing a pendent dipolarophile. These intermediates undergo intramolecular [3 + 2]-cycloadditions in a highly diastereoselective fashion to form polycyclic amines with four new stereogenic centers. Challenging substrates such as piperidine, morpholine, and thiomorpholine undergo the corresponding reactions at elevated temperatures.
