scholarly journals Bioinspired design of a robust d3-methylating agent

2020 ◽  
Vol 6 (19) ◽  
pp. eaba0946
Author(s):  
Minyan Wang ◽  
Yunfei Zhao ◽  
Yue Zhao ◽  
Zhuangzhi Shi
Keyword(s):  
Organic Molecules ◽  
Functional Group ◽  
Biologically Active ◽  
Synthetic Method ◽  
Drug Molecule ◽  
Deuterium Incorporation ◽  
Complex Molecules ◽  
Methyl Group ◽  
High Level ◽  
Excellent Selectivity

Methods to incorporate deuterium atoms into organic molecules are valuable for the pharmaceutical industry. The introduction of deuterium atoms by a synthetic method enables the direct tracing of the drug molecule without substantially altering its structure or function. The methyl group is one of the most commonly occurring carbon fragments in biologically active molecules. Here, a biomimetic design reagent, 5-(methyl-d3)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethane sulfonate (DMTT), as an analog of S-adenosylmethionine (SAM), has been developed for the selective d3-methylation of complex molecules bearing several possible reactive sites with excellent selectivity and high-level deuterium incorporation. A series of d3-methylated organic molecules and deuterated pharmaceuticals were synthesized under the mild system with excellent functional group compatibility.

scholarly journals Catalytic Synthesis of Cyclic Guanidines via Hydrogen Atom Transfer and Radical-Polar Crossover

2020 ◽  
Author(s):  
Shunya Ohuchi ◽  
Hiroki Koyama ◽  
Hiroki Shigehisa
Keyword(s):  
Hydrogen Atom ◽  
Functional Group ◽  
Hydrogen Atom Transfer ◽  
Catalytic Synthesis ◽  
Membered Ring ◽  
Biologically Active ◽  
Synthetic Method ◽  
Atom Transfer ◽  
Powerful Method ◽  
Protective Groups

Cyclic guanidines are found in many biologically active compounds and natural products. Further, the for-mation of the atypical 7-membered ring of cyclic guanidine remains challenging due to a lack of efficient preparation strategies and low yield. Herein, a catalytic synthetic method for cyclic guanidines was developed via transition-metal hydrogen atom transfer and radical-polar crossover. This mild and functional-group tolerant process enabled the cycliza-tion of an alkenyl guanidines bearing common protective groups, such as Cbz and Boc groups. This powerful method not only provided typical 5- and 6-membered rings but also the atypical 7-membered ring. The derivatization of the products afforded various heterocycles. We also investigated the selective cyclization of mono-protected or hetero-protected (TFA and Boc) alkenyl guanidines and their further derivatizations.

scholarly journals Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aijie Cai ◽  
Wenhao Yan ◽  
Xiaojun Zeng ◽  
Samson B. Zacate ◽  
Tzu-Hsuan Chao ◽  
...  
Keyword(s):  
Late Stage ◽  
Density Functional ◽  
Organic Molecules ◽  
Functional Group ◽  
Density Functional Theory Calculations ◽  
Bioactive Molecules ◽  
Mechanistic Studies ◽  
Ligand Effect ◽  
Functional Theory ◽  
Complex Molecules

AbstractOrganic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis in a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This approach simultaneously introduces CF2H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF2H radical addition. We demonstrate a broad substrate scope and a wide functional group compatibility. This scalable protocol is applied to the late-stage functionalization of complex molecules and the synthesis of CF2H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF2H species.

scholarly journals Catalytic Synthesis of Cyclic Guanidines via Hydrogen Atom Transfer and Radical-Polar Crossover

2020 ◽  
Author(s):  
Shunya Ohuchi ◽  
Hiroki Koyama ◽  
Hiroki Shigehisa
Keyword(s):  
Hydrogen Atom ◽  
Functional Group ◽  
Hydrogen Atom Transfer ◽  
Catalytic Synthesis ◽  
Membered Ring ◽  
Biologically Active ◽  
Synthetic Method ◽  
Atom Transfer ◽  
Powerful Method ◽  
Protective Groups

Cyclic guanidines are found in many biologically active compounds and natural products. Further, the for-mation of the atypical 7-membered ring of cyclic guanidine remains challenging due to a lack of efficient preparation strategies and low yield. Herein, a catalytic synthetic method for cyclic guanidines was developed via transition-metal hydrogen atom transfer and radical-polar crossover. This mild and functional-group tolerant process enabled the cycliza-tion of an alkenyl guanidines bearing common protective groups, such as Cbz and Boc groups. This powerful method not only provided typical 5- and 6-membered rings but also the atypical 7-membered ring. The derivatization of the products afforded various heterocycles. We also investigated the selective cyclization of mono-protected or hetero-protected (TFA and Boc) alkenyl guanidines and their further derivatizations.

Catalytic Synthesis of Cyclic Guanidines via Hydrogen Atom Transfer and Radical-Polar Crossover

2020 ◽  
Author(s):  
Shunya Ohuchi ◽  
Hiroki Koyama ◽  
Hiroki Shigehisa
Keyword(s):  
Hydrogen Atom ◽  
Functional Group ◽  
Hydrogen Atom Transfer ◽  
Catalytic Synthesis ◽  
Membered Ring ◽  
Biologically Active ◽  
Atom Transfer ◽  
Powerful Method ◽  
Protective Groups ◽  
The Common

A catalytic synthesis of cyclic guanidines, which are found in many biologically active compounds and natu-ral products, was developed, wherein transition-metal hydrogen atom transfer and radical-polar crossover were employed. This mild and functional-group tolerant process enabled the cyclization of alkenyl guanidines bearing common protective groups, such as Cbz and Boc. This powerful method not only provided the common 5- and 6-membered rings but also an unusual 7-membered ring. The derivatization of the products afforded various heterocycles. We also investigated the se-lective cyclization of mono-protected or hetero-protected (TFA and Boc) alkenyl guanidines and their further derivatiza-tions.

Nutrients Mediate Bioavailability and Turnover of Proteins in Mammals

2019 ◽  
Vol 20 (7) ◽  
pp. 661-665
Author(s):  
Cunxi Nie ◽  
Fei Xie ◽  
Ning Ma ◽  
Yueyu Bai ◽  
Wenju Zhang ◽  
...  
Keyword(s):  
The Body ◽  
Biologically Active ◽  
Nitrogen Excretion ◽  
Dietary Proteins ◽  
Restricted Diet ◽  
Nutritional Interventions ◽  
Body Tissues ◽  
Utilization Of Protein ◽  
High Level ◽  
Protein Restricted Diet

As a major component of biologically active compounds in the body, proteins contribute to the synthesis of body tissues for the renewal and growth of the body. The high level of dietary protein and the imbalance of amino acid (AA) composition in mammals result in metabolic disorders, inefficient utilization of protein resources and increased nitrogen excretion. Fortunately, nutritional interventions can be an effective way of attenuating the nitrogen excretion and increasing protein utilization, which include, but are not limited to, formulating the AA balance and protein-restricted diet supplementing with essential AAs, and adding probiotics in the diet. This review highlights recent advances in the turnover of dietary proteins and mammal’s metabolism for health, in order to improve protein bioavailability through nutritional approach.

scholarly journals Site-specific Umpolung amidation of carboxylic acids via triplet synergistic catalysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunyun Ning ◽  
Shuaishuai Wang ◽  
Muzi Li ◽  
Jie Han ◽  
Chengjian Zhu ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Functional Group ◽  
Amide Bond ◽  
Coupling Reagents ◽  
Complex Molecules ◽  
Bond Forming ◽  
Synergistic Catalysis ◽  
Wide Range ◽  
Amidation Reaction ◽  
Forming Methods

AbstractDevelopment of catalytic amide bond-forming methods is important because they could potentially address the existing limitations of classical methods using superstoichiometric activating reagents. In this paper, we disclose an Umpolung amidation reaction of carboxylic acids with nitroarenes and nitroalkanes enabled by the triplet synergistic catalysis of FeI2, P(V)/P(III) and photoredox catalysis, which avoids the production of byproducts from stoichiometric coupling reagents. A wide range of carboxylic acids, including aliphatic, aromatic and alkenyl acids participate smoothly in such reactions, generating structurally diverse amides in good yields (86 examples, up to 97% yield). This Umpolung amidation strategy opens a method to address challenging regioselectivity issues between nucleophilic functional groups, and complements the functional group compatibility of the classical amidation protocols. The synthetic robustness of the reaction is demonstrated by late-stage modification of complex molecules and gram-scale applications.

High-level production and one-step purification of biologically active human growth hormone in Escherichia coli

Gene ◽  
1995 ◽  
Vol 165 (2) ◽  
pp. 303-306 ◽  
Author(s):  
Reema Mukhija ◽  
Prithy Rupa ◽  
Devika Pillai ◽  
Lalit C. Garg
Keyword(s):  
Escherichia Coli ◽  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Biologically Active ◽  
One Step ◽  
High Level ◽  
Level Production

Asymmetric Hydrogenation of O-/N-Functional Group Substituted Arenes

2021 ◽  
Author(s):  
bingru shao ◽  
Lei Shi ◽  
Yong-Gui Zhou
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Asymmetric Hydrogenation ◽  
Biologically Active ◽  
Synthetic Methods

Asymmetric hydrogenation of aromatical compouds represents one of the most straightforward synthetic methods to construct important chiral cyclic skeletons that are often found in biologically active agents and natural products....

High-Level Expression of Biologically Active Human Prolactin from Recombinant Baculovirus in Insect Cells

2000 ◽  
Vol 20 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Tapas Das ◽  
Paul W. Johns ◽  
Vincent Goffin ◽  
Paul Kelly ◽  
Bruce Kelder ◽  
...  
Keyword(s):  
Insect Cells ◽  
Recombinant Baculovirus ◽  
Biologically Active ◽  
High Level Expression ◽  
Human Prolactin ◽  
High Level

scholarly journals Intermolecular 3+3 Ring Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides

2019 ◽  
Author(s):  
Jennifer Schomaker ◽  
Josephine Eshon ◽  
Kate A. Nicastri ◽  
Steven C. Schmid ◽  
William T. Raskopf ◽  
...  
Keyword(s):  
Natural Product ◽  
Functional Group ◽  
Ring Expansion ◽  
Sigmatropic Rearrangement ◽  
Reactive Intermediate ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Complex Molecules ◽  
Form Complex ◽  
Reaction Proceeds

Bicyclic aziridines undergo formal [3+3] ring expansion reactions when exposed to rhodium-bound vinyl carbenes to form complex dehydropiperidines in a highly stereocontrolled rearrangement. Mechanistic studies and DFT computations indicate the reaction proceeds through the formation of a vinyl aziridinium ylide; this reactive intermediate undergoes a concerted, asynchronous, pseudo-[1,4]- sigmatropic rearrangement to directly furnish the heterocyclic products with net retention at the new C-C bond. In combination with an asymmetric silver-catalyzed aziridination developed in our group, this method quickly delivers enantioenriched scaffolds with up to three contiguous stereocenters. The mild reaction conditions, functional group tolerance, and high stereochemical retention of this method are especially well-suited for appending piperidine motifs to natural product and complex molecules. Ultimately, our work establishes the value of underutilized aziridinium ylides as key intermediates in strategies to convert small, strained rings to larger N-heterocycles.

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