Synthesis Of Complex Molecules Research Articles

Functional characterization of the tomato HAIRPLUS gene reveals the implication of the epigenome in the control of glandular trichome formation.

Trichomes are specialised epidermal cells developed in the aerial surface of almost every terrestrial plant. These structures form physical barriers, which combined with their capability of synthesis of complex molecules, prevent plagues from spreading and confer trichomes a key role in the defence against herbivores. In this work, the tomato gene HAIRPLUS (HAP) that controls glandular trichome density in tomato plants was characterised. HAP belongs to a group of proteins involved in histone tail modifications although some also bind methylated DNA. HAP loss of function promotes epigenomic modifications in the tomato genome reflected in numerous differentially methylated cytosines and causes transcriptomic changes in hap mutant plants. Taken together, these findings demonstrate that HAP links epigenome remodelling with multicellular glandular trichome development and reveal that HAP is a valuable genomic tool for pest resistance in tomato breeding.

Recent Advances Review on Iron Complexes as Catalyst in Oxidation Reactions of Organic Compounds

The complexes of iron are found to be too reactive and are too diverse in their reactivity, when compared to the other neighbouring metals in the group. Iron complexes are used in various catalytic reactions such as oxygenation of C–H bonds, the oxidation of alcohols to aldehydes, ketones (or) carboxylic acids, the epoxidation or dihydroxylation of alkenes and oxidative coupling reactions. Efforts are taken to avoid certain disadvantages taking place during enzymatic catalysis such as the temperature and solvent sensitivity, narrow substrate scope, restricted accessibility and so on observed while using other catalysts via iron enzymes. This helped in the various synthesis of complex molecules by increase in the number of iron catalyst systems for the oxidation reactions.

Organocatalysis applied to carbohydrates: from roots to current developments.

Organocatalysis emerged in the last decade as a powerful tool for the synthesis of complex molecules. In the field of carbohydrates, it found widespread use in the synthesis of rare and non-natural carbohydrate derivatives. Additionally, it has also found important application in the stereoselective functionalization of the anomeric carbon in glycosylation reactions. These efforts culminated in the development of different types of catalysts operating through distinct activation modes that allow the selective synthesis of α- or β-glycosides even on daunting substrates. All these advances starting from its first examples in carbohydrate synthesis to the current developments in glycosylation reactions are reviewed.

Visible-light-promoted sulfenylation of 6-aminouracils under catalyst-free conditions

Visible-light-promoted reactions have proven to be a decent strategy for the synthesis of complex molecules.

Strategic elements in computer-assisted retrosynthesis: A case study of the pupukeanane natural products

Computer-assisted synthesis planning represents a growing area of research, especially for complex molecule synthesis. Here, we present a case study involving the pupukeanane natural products, which are complex, marine-derived, natural products with unique tricyclic scaffolds. Proposed routes to members of each skeletal class informed by pathways generated using the program Synthia™ are compared to previous syntheses of these molecules. In addition, novel synthesis routes are proposed to pupukeanane congeners that have not been prepared previously.

Microwave-Assisted Domino Cyclization Reactions

Background: Microwave-assisted domino cyclization reactions have attracted great interest for researchers to synthesize complex compounds in shorter times with increased yields. The domino reactions were used in various synthetic approaches and many drug deliveries in medicinal chemistry with microwave-assisted approaches. Methods: Microwave irradiation has been applied for various domino reactions. The research related to microwave-assisted domino cyclization was reviewed and the important methodologies were collected from 2011-2021. Results: Only those methodologies that involve microwave-assisted domino cyclization reactions during synthesis in a related manner have been reviewed. Along with some recent syntheses that are microwave-assisted regarding new heterocyclic moieties are summarized. Conclusion: Microwave-assisted domino cyclization reactions can be employed to quickly explore and increase molecular diversity in synthetic chemistry. We hope that this review will be helpful to find out complex molecule synthesis by microwave-assisted domino cyclization reactions. This review aimed to explain the applications of microwaves for the domino reactions from 2011- 2021. In this respect, microwave-mediated methods help researchers to make helpful studies.

Total Synthesis and Late-Stage C-H Oxidations of ent-Trachylobane Natural Products.

Herein, we present our studies to construct seven ent-trachylobane diterpenoids by employing a bioinspired two-phase synthetic strategy. The first phase provided enantioselective and scalable access to five ent-trachylobanes, of which methyl ent-trachyloban-19-oate was produced on a 300 mg scale. During the second phase, chemical C-H oxidation methods were employed to enable selective conversion to two naturally occurring higher functionalized ent-trachylobanes. The formation of regioisomeric analogs, which are currently inaccessible via enzymatic methods, reveals the potential as well as limitations of established chemical C-H oxidation protocols for complex molecule synthesis.

Total Synthesis and Late-Stage C-H Oxidations of ent-Trachylobane Natural Products.

Herein, we present our studies to construct seven ent-trachylobane diterpenoids by employing a bioinspired two-phase synthetic strategy. The first phase provided enantioselective and scalable access to five ent-trachylobanes, of which methyl ent-trachyloban-19-oate was produced on a 300 mg scale. During the second phase, chemical C–H oxidation methods were employed to enable selective conversion to two naturally occurring higher functionalized ent-trachylobanes. The formation of regioisomeric analogs, which are currently inaccessible via enzymatic methods, reveals the potential as well as limitations of established chemical C–H oxidation protocols for complex molecule synthesis.

Synthesis of Chiral Scaffolds Based on Polyfunctional Cyclobutane β‐Amino Acids

AbstractChiral scaffolds have been synthesized through selective transformations from conveniently protected cyclobutane β‐amino acids. The obtained derivatives present additional functional groups, such as hydroxyl, carboxyl, or carbon‐carbon triple bond, linked to the amino acid core through a flexible C1 or C2 alkyl fragment. The resultant molecules are highly versatile to be used as chiral precursors for the production of polyfunctional chemical platforms. These can be suitable for the synthesis of complex molecules, through condensation reactions, such as peptide coupling, dehydration between a carboxylic acid and an alcohol, or click chemistry. To illustrate some of these possibilities, two hybrid tripeptides have been prepared as examples of their synthetic potential.

Inside Cover: Synthetic Molecular Photoelectrochemistry: New Frontiers in Synthetic Applications, Mechanistic Insights and Scalability (Angew. Chem. Int. Ed. 12/2022)

Molecular photoelectrochemistry, choose your catalysis: Molecular photoelectrochemistry, allowing access to a broader window of single electron transfer chemistry in a greener way, is a rapidly expanding toolbox for synthesis and selective functionalizations of complex molecules. In their Review (DOI: 10.1002/anie.202107811), Joshua Barham et al. capture exciting synthetic opportunities, key mechanistic insights and evolving batch and flow reactor platforms allowing screening and scalability of reactions.

Thiol-Mediated α-Amino Radical Formation via Visible-Light-Activated Ion-Pair Charge-Transfer Complexes.

Visible-light-activated electron donor-acceptor complexes offer distinct reaction pathways for the synthesis of complex molecules under mild conditions. Herein, we report a method for the reductive generation of α-amino radicals via the reaction of a visible-light-activated ion-pair charge-transfer complex formed between an in situ-generated alkyl-iminium ion and a thiophenolate. This distinct activation mode is demonstrated through the development of a multicomponent coupling reaction to form substituted aminomethyl-cyclopentanes from secondary amines, cyclopropyl aldehydes, and alkenes. The operationally straightforward transformation displays broad scope and provides a means to generate cyclic amine-containing scaffolds from readily available feedstocks.

One-Pot Synthesis of Primary and Secondary Aliphatic Amines via Mild and Selective sp3 C-H Imination.

The direct replacement of sp3 C-H bonds with simple amine units (-NH2 ) remains synthetically challenging, although primary aliphatic amines are ubiquitous in medicinal chemistry and natural product synthesis. We report a mild and selective protocol for preparing primary and secondary aliphatic amines in a single pot, based on intermolecular sp3 C-H imination. The first C-H imination of diverse alkanes, this method shows useful site-selectivity within substrates bearing multiple sp3 C-H bonds. Furthermore, this reaction tolerates polar functional groups relevant for complex molecule synthesis, highlighted in the synthesis of amine pharmaceuticals and amination of natural products. We characterize a unique C-H imination mechanism based on radical rebound to an iminyl radical, supported by kinetic isotope effects, stereoablation, resubmission, and computational modeling. This work constitutes a selective method for complex amine synthesis and a new mechanistic platform for C-H amination.

Late-Stage Diversification: A Motivating Force in Organic Synthesis.

Interest in therapeutic discovery typically drives the preparation of natural product analogs, but these undertakings contribute significant advances for synthetic chemistry as well. The need for a highly efficient and scalable synthetic route to a complex molecular scaffold for diversification frequently inspires new methodological development or unique application of existing methods on structurally intricate systems. Additionally, synthetic planning with an aim toward late-stage diversification can provide access to otherwise unavailable compounds or facilitate preparation of complex molecules with diverse patterns of substitution around a shared carbon framework. For these reasons among others, programs dedicated to the diversification of natural product frameworks and other complex molecular scaffolds have been increasing in popularity, a trend likely to continue given their fruitfulness and breadth of impact. In this Perspective, we discuss our experience using late-stage diversification as a guiding principle for the synthesis of natural product analogs and reflect on the impact such efforts have on the future of complex molecule synthesis.

Single-Atom Catalysis: From Simple Reactions to the Synthesis of Complex Molecules.

To date, the scope of single-atom catalysts (SAC) in liquid-phase transformations is rather limited owing to stability issues and the inability to activate complex substances. This calls for a better design of the catalyst support that can provide a dynamic coordination environment needed for catalytic action, and yet retain robustness against leaching or aggregation. In addition, the chemical orthogonality of SAC is useful for designing tandem or multicomponent reactions, in which side reactions common to metal nanoparticles are suppressed. In this review, the intrinsic mechanism will be highlighted that controls reaction efficiency and selectivity in SAC-catalyzed pathways, as well as the structural dynamism of SAC under complex liquid-phase conditions. These mechanistic insights are helpful for the development of next-generation SAC systems for the synthesis of high-value pharmaceuticals through late-stage functionalization, sequential and multicomponent strategies.

Copper-Catalyzed Cross-Coupling of Benzylic C-H Bonds and Azoles with Controlled N-Site Selectivity.

Azoles are important motifs in medicinal chemistry, and elaboration of their structures via direct N-H/C-H coupling could have broad utility in drug discovery. The ambident reactivity of many azoles, however, presents significant selectivity challenges. Here, we report a copper-catalyzed method that achieves site-selective cross-coupling of pyrazoles and other N-H heterocycles with substrates bearing (hetero)benzylic C-H bonds. Excellent N-site selectivity is achieved, with the preferred site controlled by the identity of co-catalytic additives. This cross-coupling strategy features broad scope for both the N-H heterocycle and benzylic C-H coupling partners, enabling application of this method to complex molecule synthesis and medicinal chemistry.

Total Synthesis of (±)-Impatien A via Aza-Heck Cyclization.

The first total synthesis of the natural product impatien A is described. This concise synthesis features an aza-Heck cyclization to construct the complex spirocyclic ring system and provides a rare example of the use of aza-Heck cyclizations in complex molecule synthesis. To enable this key cyclization of an electrophilic nitrogen atom with a tetrasubstituted alkene, we utilized high-throughput experimentation to identify a new ligand and ultimately deliver impatien A in seven steps from known compounds.

Dynamic Catalytic Highly Enantioselective 1,3‐Dipolar Cycloadditions

AbstractIn dynamic covalent chemistry, reactions follow a thermodynamically controlled pathway through equilibria. Reversible covalent‐bond formation and breaking in a dynamic process enables the interconversion of products formed under kinetic control to thermodynamically more stable isomers. Notably, enantioselective catalysis of dynamic transformations has not been reported and applied in complex molecule synthesis. We describe the discovery of dynamic covalent enantioselective metal‐complex‐catalyzed 1,3‐dipolar cycloaddition reactions. We have developed a stereodivergent tandem synthesis of structurally and stereochemically complex molecules that generates eight stereocenters with high diastereo‐ and enantioselectivity through asymmetric reversible bond formation in a dynamic process in two consecutive Ag‐catalyzed 1,3‐dipolar cycloadditions of azomethine ylides with electron‐poor olefins. Time‐dependent reversible dynamic covalent‐bond formation gives enantiodivergent and diastereodivergent access to structurally complex double cycloadducts with high selectivity from a common set of reagents.

CHEMICAL AND PHARMACOLOGICAL EVOLUTION OF SOME SYNTHESIZED CHALCONES AND HETROCYCLIC COMPOUNDS

Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for the purpose of medicinal products. With centuries medicinal chemistry had emerged as a magnanimous field of science getting a facelift from the available natural compounds for synthesis of newer and complex molecules possessing medicinal activity while the transit from the earth to a synthetically furnished laboratory. Medicinal chemistry or pharmaceutical chemistry is a discipline at the intersection of chemistry and pharmacology involved with designing, synthesizing and developing pharmaceutical drugs. Chalconesis a generic term given to compounds bearing the 1,3-diarylprop2-en-1-one, which can be functionlized in the propane chain by the presence of olefinic, keto and/or hydroxyl group. Chalcones belongs to the flavonoid family. Chemically chalcones consisted of open chain flavonoids in which the two aromaticrings are joined by a three carbon a,ß-unsaturated carbonyl system (Dhar, 1981). Microorganisms are a heterogeneous group of several distinct classes of living beings. They were classified under third kingdom, theProstita. Based on differences in cellular organization and biochemistry, the kingdom prostita has been divided into two groups, Prokaryotes and Eukaryotes. Bacteria and blue green algae are prokaryotes while fungi, other algae, slime moulds and protozoa are eukaryotes. Anti-fungal drugs are among the most frequently prescribed preparations because of their fungal activity. They are widely used for the treatment of the fungal diseases such as Candidiasis and Apergillosis. These agents prevent from fungal infection. Anti-oxidant drugs are among the most frequently prescribed preparations prevent Oxidation.

CHEMICAL AND PHARMACOLOGICAL EVOLUTION OF SOME SYNTHESIZED CHALCONES AND HETROCYCLIC COMPOUNDS

Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for the purpose of medicinal products. With centuries medicinal chemistry had emerged as a magnanimous field of science getting a facelift from the available natural compounds for synthesis of newer and complex molecules possessing medicinal activity while the transit from the earth to a synthetically furnished laboratory. Medicinal chemistry or pharmaceutical chemistry is a discipline at the intersection of chemistry and pharmacology involved with designing, synthesizing and developing pharmaceutical drugs. Chalconesis a generic term given to compounds bearing the 1,3-diarylprop2-en-1-one, which can be functionlized in the propane chain by the presence of olefinic, keto and/or hydroxyl group. Chalcones belongs to the flavonoid family. Chemically chalcones consisted of open chain flavonoids in which the two aromaticrings are joined by a three carbon a,ß-unsaturated carbonyl system (Dhar, 1981). Microorganisms are a heterogeneous group of several distinct classes of living beings. They were classified under third kingdom, theProstita. Based on differences in cellular organization and biochemistry, the kingdom prostita has been divided into two groups, Prokaryotes and Eukaryotes. Bacteria and blue green algae are prokaryotes while fungi, other algae, slime moulds and protozoa are eukaryotes. Anti-fungal drugs are among the most frequently prescribed preparations because of their fungal activity. They are widely used for the treatment of the fungal diseases such as Candidiasis and Apergillosis. These agents prevent from fungal infection. Anti-oxidant drugs are among the most frequently prescribed preparations prevent Oxidation.

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Drug recalls have led to increased regulatory scrutiny into the formation and presence of nitrosamine (N-nitrosoamine) impurities in medicines. This review aims to assist the development of risk mitigation strategies by summarizing known reactions of nitrosamines, with a focus on reactions useful within the context of complex molecule synthesis. This review should serve as a useful reference and help lead to the development of chemical processes which effectively control nitrosamines.