Regio- and stereoselective addition of Brønsted acids to yndiamides: Synthesis of N,O,N- and N,S,N-trisubstituted ketene acetals

Synthesis ◽  
2021 ◽  
Author(s):  
Olivia L. Garry ◽  
Stephen J. Mansfield ◽  
Edward Anderson
Keyword(s):  
Organic Molecules ◽  
Building Blocks ◽  
Bronsted Acids ◽  
Stereoselective Addition ◽  
Regioselective Addition ◽  
Regioselective Reactions ◽  
Ketene Acetals

Yndiamides, N,N-disubstituted alkynes, are versatile building blocks for the synthesis of nitrogen-containing organic molecules. Unlike ynamides, relatives that are inherently polarized by a single nitrogen substituent, their pseudo-symmetric nature renders regioselective reactions challenging. Here we report investigations into the regioselective addition of Brønsted acids to non-symmetric yndiamides, a reaction that delivers N,O,N- and N,S,N-trisubstituted ketene acetals with excellent regio- and stereoselectivity.

A Complementary Toolbox of Iterative Methods for the Stereo­selective Synthesis of Heteroatom-Rich Motives from C1-Building Blocks

Synthesis ◽  
2018 ◽  
Vol 50 (12) ◽  
pp. 2307-2322 ◽  
Author(s):  
Christoph Hirschhäuser ◽  
Sujenth Kirupakaran ◽  
Hans-Gert Korth
Keyword(s):  
Carbon Atom ◽  
Assembly Line ◽  
Organic Molecules ◽  
Building Blocks ◽  
Chiral Auxiliary ◽  
Alkyl Chains ◽  
Stereoselective Addition ◽  
Boronic Esters ◽  
Excellent Control ◽  
Video Abstract

The ability to assemble organic molecules one carbon atom at a time has been a long-held dream for chemists. Modern boronate homologations with chiral carbenoids allow for the assembly-line synthesis of long chiral alkyl chains with excellent control over individual stereocenters. Nevertheless, heteroatom rich motives present a serious synthetic challenge to this approach. Interestingly, older methods based on substrate-controlled homologations of chiral boronic esters or umpolung of a carbonyl nucleophile can offer complementary solutions. A combination of these approaches might thus extend the range of possible targets currently within grasp of a C1-based synthesis. Link to video abstract: https://www.youtube.com/watch?v=PH_HBrqQwtg .1 Introduction2 Substrate Control: Stereoselective Addition of d1-Reagents to Aldehydes­3 Stereocontrol by Chiral Auxiliary/Director: The Matteson Boronate Homologation4 Reagent Control: Moving Chiral Information to the Carbenoid5 Conclusions and Outlook

scholarly journals A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Organics ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 107-117
Author(s):  
Mattia Forchetta ◽  
Valeria Conte ◽  
Giulia Fiorani ◽  
Pierluca Galloni ◽  
Federica Sabuzi
Keyword(s):  
Metal Oxides ◽  
Phosphonic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Reaction Conditions ◽  
Phosphonic Acids ◽  
Sustainable Improvement ◽  
Phosphonate Esters ◽  
First Time ◽  
Complex Organic

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications.

scholarly journals Chiroptical activity of hydroxycarboxylic acids with implications for the origin of biological homochirality

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jana Bocková ◽  
Nykola C. Jones ◽  
Uwe J. Meierhenrich ◽  
Søren V. Hoffmann ◽  
Cornelia Meinert
Keyword(s):  
Amino Acids ◽  
Lactic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Aliphatic Chain ◽  
Monocarboxylic Acids ◽  
Hydroxycarboxylic Acids ◽  
Polarised Light ◽  
Suitable Target ◽  
Anisotropy Spectra

AbstractCircularly polarised light (CPL) interacting with interstellar organic molecules might have imparted chiral bias and hence preluded prebiotic evolution of biomolecular homochirality. The l-enrichment of extra-terrestrial amino acids in meteorites, as opposed to no detectable excess in monocarboxylic acids and amines, has previously been attributed to their intrinsic interaction with stellar CPL revealed by substantial differences in their chiroptical signals. Recent analyses of meteoritic hydroxycarboxylic acids (HCAs) – potential co-building blocks of ancestral proto-peptides – indicated a chiral bias toward the l-enantiomer of lactic acid. Here we report on novel anisotropy spectra of several HCAs using a synchrotron radiation electronic circular dichroism spectrophotometer to support the re-evaluation of chiral biomarkers of extra-terrestrial origin in the context of absolute photochirogenesis. We found that irradiation by CPL which would yield l-excess in amino acids would also yield l-excess in aliphatic chain HCAs, including lactic acid and mandelic acid, in the examined conditions. Only tartaric acid would show “unnatural” d-enrichment, which makes it a suitable target compound for further assessing the relevance of the CPL scenario.

Efficient labeling of organic molecules using 13C elemental carbon: universal access to 13C2-labeled synthetic building blocks, polymers and pharmaceuticals

2020 ◽  
Vol 7 (4) ◽  
pp. 638-647 ◽  
Author(s):  
Maria S. Ledovskaya ◽  
Vladimir V. Voronin ◽  
Konstantin S. Rodygin ◽  
Valentine P. Ananikov
Keyword(s):  
Elemental Carbon ◽  
Organic Molecules ◽  
Universal Access ◽  
Calcium Carbide ◽  
Building Blocks ◽  
Synthetic Methodology ◽  
Vinyl Derivatives

Synthetic methodology enabled by 13C-elemental carbon is reported. Calcium carbide Ca13C2 was applied to introduce a universal 13C2 unit in the synthesis of labeled alkynes, O,S,N-vinyl derivatives, labeled polymers and 13C2-pyridazine drug core.

scholarly journals Fullerenes in the IC 348 star cluster of the Perseus Molecular Cloud

2019 ◽  
Author(s):  
S Iglesias-Groth
Keyword(s):  
Molecular Cloud ◽  
Organic Molecules ◽  
Protoplanetary Disks ◽  
Building Blocks ◽  
Cluster Emission ◽  
Star Forming ◽  
Available Carbon ◽  
Prebiotic Molecules ◽  
Complex Organic ◽  
Early Phases

Abstract We present the detection of fullerenes C60 and C70 in the star-forming region IC 348 of the Perseus molecular cloud. Mid-IR vibrational transitions of C60 and C70 in emission are found in Spitzer IRS spectra of individual stars (LRLL 1, 2, 58), in the averaged spectrum of three other cluster stars (LRLL 21, 31 and 67) and in spectra obtained at four interstellar locations distributed across the IC 348 region. Fullerene bands appear widely distributed in this region with higher strength in the lines-of-sight of stars at the core of the cluster. Emission features consistent with three most intense bands of the C$_{60}^+$ and with one of C$_{60}^-$ are also found in several spectra, and if ascribed to these ionized species it would imply ionization fractions at 20 and 10 %, respectively. The stars under consideration host protoplanetary disks, however the spatial resolution of the spectra is not sufficient to disentangle the presence of fullerenes in them. If fullerene abundances in the cloud were representative of IC 348 protoplanetary disks, C60, the most abundant of the two species, could host ∼ 0.1 % of the total available carbon in the disks. This should encourage dedicated searches in young disks with upcoming facilities as JWST. Fullerenes provide a reservoir of pentagonal and hexagonal carbon rings which could be important as building blocks of prebiotic molecules. Accretion of these robust molecules in early phases of planet formation may contribute to the formation of complex organic molecules in young planets.

Ordered Assembling of Size and Shape Selected Nanocrystals

1998 ◽  
Vol 4 (S2) ◽  
pp. 728-729
Author(s):  
Z.L. Wang
Keyword(s):  
Organic Molecules ◽  
Three Dimensional ◽  
Building Blocks ◽  
Organic Coating ◽  
Self Organization ◽  
Functional Specificity ◽  
Orientation Order ◽  
Self Assembled ◽  
Superlattice Structures ◽  
Physical And Chemical

Nanoparticles and the physical and chemical functional specificity and selectivity they possess, suggest them as ideal building blocks for two- and three-dimensional cluster self-assembled superlattice structures, in which the particles behave as well-defined molecular matter and they are arranged with long-range translation and even orientation order [1]. Self-assembled arrays involve self-organization into monolayers, thin films, and superlattices of size-selected nanoclusters encapsulated in protective compact organic coating. The macroscopic properties of the nanocrystal superlattice (NCS) are determined not only by the properties of each individual particle but by the coupling/interaction between nanocrystals interconnected and isolated by a monolayer of thin organic molecules.Periodic packing of nanocrystals is different from the 3-D packing of atoms. First, to an excellent approximation atoms are spherical, while nanoparticles can be faceted polyhedra, thus, the 3-D packing of particles can be critically affected by their shapes and sizes.

scholarly journals The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery

2020 ◽  
Vol 74 (4) ◽  
pp. 241-246 ◽  
Author(s):  
Kris Meier ◽  
Sven Bühlmann ◽  
Josep Arús-Pous ◽  
Jean-Louis Reymond
Keyword(s):  
Drug Discovery ◽  
Medicinal Chemistry ◽  
Organic Molecules ◽  
Chemical Space ◽  
Building Blocks ◽  
Chiral Molecules ◽  
Hydrogen Atoms ◽  
Quaternary Centers ◽  
Medical Needs ◽  
Unmet Medical Needs

Drug discovery is in constant need of new molecules to develop drugs addressing unmet medical needs. To assess the chemical space available for drug design, our group investigates the generated databases (GDBs) listing all possible organic molecules up to a defined size, the largest of which is GDB-17 featuring 166.4 billion molecules up to 17 non-hydrogen atoms. While known drugs and bioactive compounds are mostly aromatic and planar, the GDBs contain a plethora of non-aromatic 3D-shaped molecules, which are very useful for drug discovery since they generally have more desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Here we review GDB enumeration methods and the selection and synthesis of GDB molecules as modulators of ion channels. We summarize the constitution of GDB subsets focusing on fragments (FDB17), medicinal chemistry (GDBMedChem) and ChEMBL-like molecules (GDBChEMBL), and the ring system database GDB4c as a rich source of novel 3D-shaped chiral molecules containing quaternary centers, such as the recently reported trinorbornane.

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