scholarly journals Concise syntheses of GB22, GB13 and himgaline by cross-coupling and complete reduction

2021 ◽  
Author(s):  
Eleanor Landwehr ◽  
Meghan Baker ◽  
Takuya Oguma ◽  
Hannah Burdge ◽  
Takahiro Kawajiri ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Cross Coupling ◽  
Building Blocks ◽  
Class Iii ◽  
Stereoselective Reduction ◽  
Complete Reduction ◽  
Variable Distribution ◽  
High Fraction

Class III neuroactive metabolites from the bark of Galbu-limima belgraveana occur in variable distribution and are not easily procured by chemical synthesis. Here we decrease the synthetic burden of himgaline to nearly one-third of the prior best (7–9 vs. 19–31 steps) by cross-coupling high fraction aromatic (FAr) building blocks followed by com-plete, stereoselective reduction to high-fraction sp3 (Fsp3) products. This short entry into GB alkaloid space allows its extensive exploration and biological interrogation.

scholarly journals Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

2020 ◽  
Author(s):  
Mingyu Liu ◽  
Tianhua Tang ◽  
Omar Apolinar ◽  
Rei Matsuura ◽  
Carl Busacca ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Large Scale ◽  
Bond Formation ◽  
Cross Coupling ◽  
Building Blocks ◽  
Commercial Production ◽  
Catalytic Cycle ◽  
Catalyst Loading ◽  
Terminal Alkynes ◽  
Catalytic Method

Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires pre-functionalized building blocks. However, the requisite pre-functionalization steps undermine the efficiency of multi-step synthetic sequences, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without pre-functionalized building blocks. This method is facilitated by a tailored P,N-ligand that enables regioselective coupling and suppresses secondary <i>E</i>/<i>Z</i>-isomerization of the product. The transformation enables several classes of unactivated internal acceptor alkynes to be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. The reaction is scalable and can operate effectively with 0.5 mol% catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.

scholarly journals Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

2020 ◽  
Author(s):  
Mingyu Liu ◽  
Tianhua Tang ◽  
Omar Apolinar ◽  
Rei Matsuura ◽  
Carl Busacca ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Large Scale ◽  
Bond Formation ◽  
Cross Coupling ◽  
Building Blocks ◽  
Commercial Production ◽  
Catalytic Cycle ◽  
Catalyst Loading ◽  
Terminal Alkynes ◽  
Catalytic Method

Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires pre-functionalized building blocks. However, the requisite pre-functionalization steps undermine the efficiency of multi-step synthetic sequences, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without pre-functionalized building blocks. This method is facilitated by a tailored P,N-ligand that enables regioselective coupling and suppresses secondary <i>E</i>/<i>Z</i>-isomerization of the product. The transformation enables several classes of unactivated internal acceptor alkynes to be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. The reaction is scalable and can operate effectively with 0.5 mol% catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.

Concise Synthesis of GB22 by Endo-Selective Siloxycyclopropane Arylation

2019 ◽  
Author(s):  
Hannah E. Burdge ◽  
Takuya Oguma ◽  
Takahiro Kawajiri ◽  
Ryan Shenvi
Keyword(s):  
Intramolecular Cyclization ◽  
Cross Coupling ◽  
Building Blocks ◽  
Ring Expansion ◽  
Dual Catalysis ◽  
Acid Labile

<div><div><div><p>The first synthesis of GB22 was accomplished by a con- cise, modular route. Two building blocks converged in a novel sp3-sp2 attached-ring coupling that used Ir/Ni dual-catalysis to reverse the regioselectivity of siloxycy- clopropane arylation. This cross-coupling proved general to access β-substituted tetralones via ring-expansion of indanone-derived siloxycyclopropanes. The congested, bridging rings of the GB alkaloids were completed using an aluminum-HFIP complex that effected intramolecular cyclization of an acid-labile substrate.</p></div></div></div>

Concise Synthesis of GB22 by Endo-Selective Siloxycyclopropane Arylation

2019 ◽  
Author(s):  
Hannah E. Burdge ◽  
Takuya Oguma ◽  
Takahiro Kawajiri ◽  
Ryan Shenvi
Keyword(s):  
Intramolecular Cyclization ◽  
Cross Coupling ◽  
Building Blocks ◽  
Ring Expansion ◽  
Dual Catalysis ◽  
Acid Labile

<div><div><div><p>The first synthesis of GB22 was accomplished by a con- cise, modular route. Two building blocks converged in a novel sp3-sp2 attached-ring coupling that used Ir/Ni dual-catalysis to reverse the regioselectivity of siloxycy- clopropane arylation. This cross-coupling proved general to access β-substituted tetralones via ring-expansion of indanone-derived siloxycyclopropanes. The congested, bridging rings of the GB alkaloids were completed using an aluminum-HFIP complex that effected intramolecular cyclization of an acid-labile substrate.</p></div></div></div>

Modular, Stereocontrolled Cβ–H/Cα–C Activation of Alkyl Carboxylic Acids

2019 ◽  
Author(s):  
Ming Shang ◽  
Karla S. Feu ◽  
Julien C. Vantourout ◽  
Lisa M. Barton ◽  
Heather L. Osswald ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Heterocyclic Compounds ◽  
Cross Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Carbon Centers ◽  
Drug Candidates ◽  
Rapid Diversification ◽  
Directing Group ◽  
Compound Series

<div> <div> <div> <p>The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series. </p> </div> </div> </div>

Development of Strategies for Glycopeptide Synthesis: An Overview on the Glycosidic Linkage

2020 ◽  
Vol 24 (21) ◽  
pp. 2475-2497
Author(s):  
Andrea Verónica Rodríguez-Mayor ◽  
German Jesid Peralta-Camacho ◽  
Karen Johanna Cárdenas-Martínez ◽  
Javier Eduardo García-Castañeda
Keyword(s):  
Chemical Synthesis ◽  
Solid Phase ◽  
Building Blocks ◽  
Heterogeneous Environments ◽  
Phase Synthesis ◽  
Low Concentrations ◽  
Biological Sources ◽  
Synthetic Routes ◽  
The Impact ◽  
Potential Use

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

scholarly journals Fluorinated Iron(ii) clathrochelate units in metalorganic based copolymers: improved porosity, iodine uptake, and dye adsorption properties

RSC Advances ◽  
2021 ◽  
Vol 11 (25) ◽  
pp. 14986-14995
Author(s):  
Suchetha Shetty ◽  
Noorullah Baig ◽  
Atikur Hassan ◽  
Saleh Al-Mousawi ◽  
Neeladri Das ◽  
...  
Keyword(s):  
Dye Adsorption ◽  
Coupling Reaction ◽  
Cross Coupling ◽  
Building Blocks ◽  
Adsorption Properties ◽  
Iodine Uptake ◽  
Cross Coupling Reaction ◽  
Palladium Catalyzed

We report the synthesis of metalorganic copolymers made from the palladium catalyzed Sonogashira cross-coupling reaction between various iron(ii) clathrochelate building blocks with diethynyl–triptycene and fluorene derivatives.

scholarly journals Synthesis of π-Conjugated Polymers Containing Benzotriazole Units via Palladium-Catalyzed Direct C-H Cross-Coupling Polycondensation for OLEDs Applications

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 254
Author(s):  
Dong Han ◽  
Jingwen Li ◽  
Qiang Zhang ◽  
Zewang He ◽  
Zhiwei Wu ◽  
...  
Keyword(s):  
Conjugated Polymers ◽  
Quantum Efficiency ◽  
Cross Coupling ◽  
Building Blocks ◽  
Gravimetric Analysis ◽  
19F Nmr Spectra ◽  
Light Emitting ◽  
Molecular Weights ◽  
Palladium Catalyzed ◽  
Red Luminescence

Four D-π-A conjugated polymers, namely P1–P4, which contain benzotriazole building blocks in their backbone as acceptor, are synthesized via palladium-catalyzed direct C-H cross-coupling polycondensation of 5,6-difluorobenzotriazole with different thiophene derivatives, including 3-octylthiophene, 2,2’-bithiophene, thieno[3,4-b][1,4]dioxine, and 4,4-dioctyl-4H-silolo-[3,2-b:4,5-b’]dithiophene as donor units, respectively. Taking the polymer P1 as an example, the chemical structure of the polymer is demonstrated by 1H and 19F NMR spectra. The optical, electrochemical, and thermal properties of these polymers are assessed by UV–vis absorption and fluorescence spectroscopy, cyclic voltammetry (CV), and thermal gravimetric analysis (TGA), respectively. DFT simulations of all polymers are also performed to understand their physicochemical properties. Furthermore, P1 and P2, which have relatively higher molecular weights and better fluorescent quantum efficiency than those of P3 and P4, are utilized as lighting emitters for organic light-emitting diodes (OLEDs), affording promising green and red luminescence with 0.07% and 0.14% of maximum external quantum efficiency, respectively, based on a device with an architecture of ITO/PEDOT:PSS/PTAA/the polymer emitting layer/TPBi/LiF/Al.

Pyrido[1,2-a]pyrazine - Startprodukte für regioselektive Ringtransformationen und supramolekulare Architekturen / Pyrido[1,2-a]pyrazines - Starting Materials for Regioselective Ringtransformation Reactions and Supramolecular Architectures

2002 ◽  
Vol 57 (4) ◽  
pp. 471-478 ◽  
Author(s):  
D. Müller ◽  
B. Frank ◽  
R. Beckert ◽  
H. Görls
Keyword(s):  
Cycloaddition Reaction ◽  
Coupling Reaction ◽  
Cross Coupling ◽  
Building Blocks ◽  
Ring Transformation ◽  
Supramolecular Architectures ◽  
Cross Coupling Reaction ◽  
Metal Catalyzed

The easily available pyrido[1,2-a]pyrazines of type 1 are versatile building blocks for ring transformation reactions.W ith heterocyclic quinones such as quinoline-2,5,8-triones 4a-c, a highly regioselective [4+2]-cycloaddition reaction takes place in the first step, followed by a ring transformation cascade.T he 1,6-diazaanthracene-2,9,10-triones 5a-e, which possess an additional bipyridine substructure, could be isolated as main products.In order to modify the starting products of type 1, a metal-catalyzed cross-coupling reaction with acetylenic benzoic esters 9a,b has been performed.T he modified pyridopyrazines 10a,b which were obtained in good yields could be transformed by analogy to 1a,b into ring-fused heterocyclic quinones 12a,b.

scholarly journals Synthetically Accessible Virtual Inventory (SAVI)

2020 ◽  
Author(s):  
Hitesh Patel ◽  
Wolf Ihlenfeldt ◽  
Philip Judson ◽  
Yurii S. Moroz ◽  
Yuri Pevzner ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Chemical Synthesis ◽  
Programming Languages ◽  
Expert Knowledge ◽  
Scoring Systems ◽  
Building Blocks ◽  
Single Step

We have made available a database of over 1 billion compounds predicted to be easily synthesizable. They have been created by a set of transforms based on an adaptation and extension of the CHMTRN/PATRAN programming languages describing chemical synthesis expert knowledge, which originally stem from the LHASA project. The chemoinformatics toolkit CACTVS was used to apply a total of 53 transforms to about 150,000 readily available building blocks (enamine.net). Only single-step, two-reactant syntheses were calculated for this database even though the technology can execute multi-step reactions. The possibility to incorporate scoring systems in CHMTRN allowed us to subdivide the database of 1.75 billion compounds in sets according to their predicted synthesizability, with the most-synthesizable class comprising 1.09 billion synthetic products. Properties calculated for all SAVI products show that the database should be well-suited for drug discovery. It is being made publicly available for free download from https://cactus.nci.nih.gov/download/savi_download/.

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