The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Pei-qiang Huang - One of the best experts on this subject based on the ideXlab platform.
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Procedure-Economical, Enantioselective Total Syntheses of Polycyclic Natural Products and Analogues Containing a 3a-Hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic Acid Residue
Synlett, 2020Co-Authors: Pei-qiang HuangAbstract:The 3a-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid (HPIC) residue and its aza-analogue are found in many bioactive natural products. In this account, short divergent total syntheses of several such natural products, diastereomers and analogues are described. It is demonstrated that by appropriate combination of different efficient tactics such as biomimetic/bio-inspired synthesis, chemo/regioselective reactions, umpolung of regioselectivity and/or reactivity, and tandem reactions, the enantioselective syntheses of polycyclic molecules such as (+)-Asperlicin E and (–)-robustanoids A and B can be achieved in a protecting-group-free and redox-economical manner, in only three to four steps starting from l -tryptophan. 1 Introduction 2 Strategic Considerations 2.1 Occurrence of HO-HPIC and HO-aza-HPIC Residues in Natural Products 2.2 Biosyntheses of HO-HPIC and HO-aza-HPIC Residues 2.3 Chemical Syntheses of HO-HPIC and HO-aza-HPIC Residues 3 Procedure-Economical Syntheses of HO-HPIC-Containing Natural Products 3.1 Protecting-Group-Free Syntheses of Asperlicin E, Its Diastereomer, and an Analogue 3.2 Divergent Syntheses of (–)-Robustanoids A and B, a Diastereomer, and Analogues 4 Conclusion and Future Perspectives
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Low‐Valent Titanium‐Mediated Enantioselective Synthesis of Quinazolinone Alkaloids Circumdatins F, H, and Analogs
Chinese Journal of Chemistry, 2015Co-Authors: Shi-peng Luo, Yu Wang, Hui Geng, Pei-qiang HuangAbstract:We report the concise and protecting-group-free enantioselective total syntheses of circumdatins F and H. In view of the extreme importance of analogs of quinazolinone alkaloids in drug research and discovery, four analogs of bioactive quinazolinobenzodiazepine alkaloids, including demethoxycircumdatin H (12) and N-demethylbenzomalvin A (13), have been synthesized. The method is based on the low-valent titanium-promoted intramolecular reductive coupling of imides with o-nitrobenzimides, which yielded quinazolino[3,2-a][1,4]benzodiazepines under mild conditions. In addition, heptacyclic dehydraAsperlicin E (16) has been synthesized from Asperlicin C by a NCS-mediated dehydra-cyclization reaction.
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Procedure—economical enantioselective total syntheses of Asperlicins C and E
Tetrahedron Letters, 2015Co-Authors: Pei-qiang Huang, Yu Wang, Shi-peng Luo, Hui Geng, Yuan-ping Ruan, Ai-e WangAbstract:We report a procedure—economical method for the highly enantioselective and protecting-group free total syntheses of nonpeptidal CCK antagonists Asperlicins C and E. Starting from l-tryptophan, the synthesis of Asperlicin C has been achieved in three steps, which features the low-valent titanium (LVT: TiCl4–Zn combination)-mediated reductive cyclization of o-nitrobenzamide to construct the (3H)-quinazolin-4-one moiety. This is the first employment of LVT for the synthesis of Asperlicin C, which allowed accessing Asperlicin C in >99% enantioselectivity. Asperlicin C was converted, in one-pot, into Asperlicin E and 2,3-di-epi-Asperlicin E by dimethyl dioxirane (DMDO)-mediated tandem reactions. The use of DMDO as a green, cheap, and easily available oxidant to replace the photochemical method renders the synthesis of Asperlicin E experimentally convenient.
Ai-e Wang - One of the best experts on this subject based on the ideXlab platform.
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Procedure—economical enantioselective total syntheses of Asperlicins C and E
Tetrahedron Letters, 2015Co-Authors: Pei-qiang Huang, Yu Wang, Shi-peng Luo, Hui Geng, Yuan-ping Ruan, Ai-e WangAbstract:We report a procedure—economical method for the highly enantioselective and protecting-group free total syntheses of nonpeptidal CCK antagonists Asperlicins C and E. Starting from l-tryptophan, the synthesis of Asperlicin C has been achieved in three steps, which features the low-valent titanium (LVT: TiCl4–Zn combination)-mediated reductive cyclization of o-nitrobenzamide to construct the (3H)-quinazolin-4-one moiety. This is the first employment of LVT for the synthesis of Asperlicin C, which allowed accessing Asperlicin C in >99% enantioselectivity. Asperlicin C was converted, in one-pot, into Asperlicin E and 2,3-di-epi-Asperlicin E by dimethyl dioxirane (DMDO)-mediated tandem reactions. The use of DMDO as a green, cheap, and easily available oxidant to replace the photochemical method renders the synthesis of Asperlicin E experimentally convenient.
Christopher T. Walsh - One of the best experts on this subject based on the ideXlab platform.
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In Vitro Reconstitution of Metabolic Pathways: Insights into Nature's Chemical Logic.
Synlett : accounts and rapid communications in synthetic organic chemistry, 2015Co-Authors: Brian Lowry, Christopher T. Walsh, Chaitan KhoslaAbstract:In vitro analysis of metabolic pathways is becoming a powerful method for gaining a deeper understanding of nature’s core biochemical transformations. Through the astounding advances in biotechnology, the purification of the enzymatic components of a given metabolic pathway is becoming a tractable problem; such in vitro studies permit scientists to capture the fine details of the mechanisms, kinetics, and identities of organic products of enzymatic reactions. In this review, we describe eleven metabolic pathways that have been the subject of recently reported in vitro reconstitution studies. In addition, we have selected and analyzed a subset of four case studies within these eleven examples that exemplify the remarkable organic chemistry that occurs within biological systems. These examples serves as tangible reminders that nature’s biochemical routes obey the fundamental principles of organic chemistry, as their chemical mechanisms are reminiscent of those occurring in conventional synthetic organic routes. The illustrations of biosynthetic chemistry presented in this review might inspire the development of biomimetic chemistries involving abiotic chemical techniques. 1 Introduction 2 Bacterial Metabolites 2.1 Fatty Acids 2.2 Farnesene 2.3 O-Polysaccharides 3 Plant Metabolites 3.1 Dhurrin 3.2 Camalexin 4 Polyketides and Nonribosomal Peptides 4.1 Aromatic Polyketides 4.1.1 Actinorhodin-Derived Polyketides 4.1.2 Enterocin 4.2 Fungal Polyketides 4.2.1 Norsolorinic Acid 4.2.2 Dihydromonacolin L 4.3 Assembly Line Polyketides and Nonribosomal Peptides 4.3.1 6-Deoxyerythronolide B 4.3.2 Asperlicin 5 Discussion of Chemical Insights 5.1 Allylic Carbocation Chemistry Drives Farnesene Synthesis 5.2 Multifunctional Oxidation Chemistry of Cytochrome P450 Enzymes 5.3 A Remarkable Favorskiiase Enzyme Within Enterocin Biosynthesis 5.4 Diels–Alder Chemistry Appears in Biology 6 Concluding Remarks
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An Iterative, Bimodular Nonribosomal Peptide Synthetase that Converts Anthranilate and Tryptophan into Tetracyclic Asperlicins
Chemistry & biology, 2013Co-Authors: Xue Gao, Wei Jiang, Gonzalo Jiménez-osés, Moon Seok Choi, Kendall N. Houk, Yi Tang, Christopher T. WalshAbstract:The bimodular 276 kDa nonribosomal peptide synthetase AspA from Aspergillus alliaceus, heterologously expressed in Saccharomyces cerevisiae, converts tryptophan and two molecules of the aromatic β-amino acid anthranilate (Ant) into a pair of tetracyclic peptidyl alkaloids Asperlicin C and D in a ratio of 10:1. The first module of AspA activates and processes two molecules of Ant iteratively to generate a tethered Ant-Ant-Trp-S-enzyme intermediate on module two. Release is postulated to involve tandem cyclizations, in which the first step is the macrocyclization of the linear tripeptidyl-S-enzyme, by the terminal condensation (CT) domain to generate the regioisomeric tetracyclic Asperlicin scaffolds. Computational analysis of the transannular cyclization of the 11-membered macrocyclic intermediate shows that Asperlicin C is the kinetically favored product due to the high stability of a conformation resembling the transition state for cyclization, while Asperlicin D is thermodynamically more stable.
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Assembly of Asperlicin peptidyl alkaloids from anthranilate and tryptophan: a two-enzyme pathway generates heptacyclic scaffold complexity in Asperlicin E.
Journal of the American Chemical Society, 2012Co-Authors: Stuart W. Haynes, Xue Gao, Yi Tang, Christopher T. WalshAbstract:Members of the Asperlicin family of fungal metabolites produced by Aspergillus alliaceus are known potent CCKA antagonists. Herein, we report the identification of the gene cluster responsible for directing their biosynthesis. We validate and probe the pathway by genetic manipulation, and provide the first biochemical characterization of the oxidative cyclization en route to the heptacyclic Asperlicin E by reconstituting the activity of the FAD depend monooxygenase AspB. This report provides the first genetic characterization of a NRPS assembly line that efficiently activates two anthranilate building blocks and illustrates the remarkably efficient biosynthesis of the complex heptacyclic Asperlicin E.
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Assembly of Asperlicin Peptidyl Alkaloids from Anthranilate and Tryptophan: A Two-Enzyme Pathway Generates Heptacyclic Scaffold Complexity in Asperlicin E
2012Co-Authors: Stuart W. Haynes, Xue Gao, Yi Tang, Christopher T. WalshAbstract:Members of the Asperlicin family of fungal metabolites produced by Aspergillus alliaceus are known potent CCKA antagonists. Herein, we report the identification of the gene cluster responsible for directing their biosynthesis. We validate and probe the pathway by genetic manipulation, and provide the first biochemical characterization of the oxidative cyclization en route to the heptacyclic Asperlicin E by reconstituting the activity of the FAD depend monooxygenase AspB. This report provides the first genetic characterization of a NRPS assembly line that efficiently activates two anthranilate building blocks and illustrates the remarkably efficient biosynthesis of the complex heptacyclic Asperlicin E
Jacques Delarge - One of the best experts on this subject based on the ideXlab platform.
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Pyridothiadiazinedioxides structurally related to quinazolinones cholecystokinin/gastrin receptor ligands: synthesis and biological evaluation
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 1998Co-Authors: Bernard Pirotte, Pascal De Tullio, Tchao Podona, Ousmane Diouf, D. Dewalque, Philippe Neven, Bernard Masereel, Daniel-henri Caignard P, P. Renard, Jacques DelargeAbstract:The synthesis of 3-aralkyl-4-aryl-4H-, 3-aralkylamino-4-aryl-4H- and 3-aralkylsulfanyl-4-aryl-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides is described. Moreover, the affinity of the different compounds towards the cholecystokinin CCK-A and CCK-B receptors was evaluated. For selected compounds, affinity on the two receptor subtypes was expressed in the micromolar range. This was comparable to the affinity observed with the naturally occurring CCK receptor antagonist Asperlicin.
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Synthesis and biological evaluation of new 3-aralkylamino-2-aryl-2H-1,2,4-pyridothiadiazine 1,1-dioxides as potential CCK receptor ligands
The Journal of pharmacy and pharmacology, 1997Co-Authors: Pascal De Tullio, Bernard Pirotte, Tchao Podona, Ousmane Diouf, D. Dewalque, Philippe Neven, Bernard Masereel, Daniel H. Caignard, Pierre Renard, Jacques DelargeAbstract:A series of 2-aralkyl-4H-pyridothiadiazine 1,1-dioxides and 3-aralkylamino-2-aryl-2H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to quinazolinone CCK receptor antagonists were synthesized and evaluated as CCK-A and CCK-B receptor ligands. The compounds were effective as cholecystokinin-ligands in the micromolar range of concentration, c.f. the cholecystokinin receptor antagonists Asperlicin, lorglumide or benzotript, and were thus less potent than the best quinazolinones previously reported. Although the compounds were unsuitable for drug use, the work contributed to our understanding of the chemistry of unusual 2,3-disubstituted pyridothiadiazinedioxides.
Lina S. Al-qaisi - One of the best experts on this subject based on the ideXlab platform.
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Total synthesis of Asperlicin D
Tetrahedron Letters, 2006Co-Authors: Naim H. Al-said, Lina S. Al-qaisiAbstract:Abstract Cyclodehydration of a linear tripeptide furnished the first total synthesis of Asperlicin D in moderate yield. The cyclodehydration process was triggered by an intramolecular nucleophilic acyl substitution and an intramolecular aza-Wittig reaction.
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A biomimetic approach to quinazolino [3,2-d] [1,4]benzodiazepine ring system : The first total synthesis of Asperlicin D
Acta Chimica Slovenica, 2006Co-Authors: Naim H. Al-said, Lina S. Al-qaisiAbstract:Lewis acid (MgCl 2 , ZnCl 2 ) mediated cyclodehydration of a linear tripeptide comprised of three amino acid units in the order of anthranilic-anthranilic-glycine (C-terminal anthranoyl-anthranilate methyl ester) furnished the tricyclic quinazolino[3,2-d][1,4]benzodiazepine ring system found in various biologically active natural alkaloids. This methodology, implemented with a tripeptide encompassing the sequence ofanthranilic-anthranilic-tryptophan methyl ester, furnish the first total synthesis of Asperlicin D.
