ChemInform Abstract: One-Pot Four-Component Synthesis of 4-Hydrazinothiazoles: Novel Scaffolds for Drug Discovery.

ChemInform ◽  
2015 ◽  
Vol 46 (11) ◽  
pp. no-no
Author(s):  
Sarah Titus ◽  
Kumaran G. Sreejalekshmi
Keyword(s):  
Drug Discovery ◽  
One Pot

scholarly journals General synthetic strategy for regioselective ultrafast formation of disulfide bonds in peptides and proteins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shay Laps ◽  
Fatima Atamleh ◽  
Guy Kamnesky ◽  
Hao Sun ◽  
Ashraf Brik
Keyword(s):  
Drug Discovery ◽  
Disulfide Bonds ◽  
Unsolved Problem ◽  
De Novo ◽  
Therapeutic Potential ◽  
Selective Activation ◽  
One Pot ◽  
Synthetic Strategy ◽  
The One ◽  
Game Changer

AbstractDespite six decades of efforts to synthesize peptides and proteins bearing multiple disulfide bonds, this synthetic challenge remains an unsolved problem in most targets (e.g., knotted mini proteins). Here we show a de novo general synthetic strategy for the ultrafast, high-yielding formation of two and three disulfide bonds in peptides and proteins. We develop an approach based on the combination of a small molecule, ultraviolet-light, and palladium for chemo- and regio-selective activation of cysteine, which enables the one-pot formation of multiple disulfide bonds in various peptides and proteins. We prepare bioactive targets of high therapeutic potential, including conotoxin, RANTES, EETI-II, and plectasin peptides and the linaclotide drug. We anticipate that this strategy will be a game-changer in preparing millions of inaccessible targets for drug discovery.

Facile Approach to Geminal Heterodihalogenation. One-Pot Synthesis of α-Bromo-α-Chloro Ketones

Synlett ◽  
2020 ◽  
Vol 31 (14) ◽  
pp. 1430-1434
Author(s):  
Ming Bian ◽  
Jin-feng Zhou ◽  
Dong-min Tang
Keyword(s):  
Drug Discovery ◽  
Dimethyl Sulfoxide ◽  
Functional Groups ◽  
Methyl Ketones ◽  
One Pot ◽  
One Pot Synthesis ◽  
Operational Simplicity

An efficient and practical protocol for the geminal heterodihalogenation of methyl ketones by using readily available dimethyl sulfoxide and a combination of HCl and HBr is reported. Control experiments suggested that the acidity of the solution, as well as the oxidizing ability and nucleophilicity of the dimethyl sulfoxide might work cooperatively in ensuring the success of the tandem substitution. Its operational simplicity, easy accessibility, and mild oxidative conditions suggest that the present strategy might be useful for the assembly of bromochloromethyl functional groups in drug discovery.

Synthesis of Pyrazolofuropyrazine via One-Pot SNAr Reaction and Intramolecular Direct C–H Arylation

Synthesis ◽  
2018 ◽  
Vol 50 (07) ◽  
pp. 1493-1498 ◽  
Author(s):  
Shinichiro Fuse ◽  
Hiroyuki Nakamura ◽  
Megumi Inaba ◽  
Shinichi Sato ◽  
Manjusha Joshi
Keyword(s):  
Drug Discovery ◽  
Rapid Development ◽  
Ring System ◽  
Biologically Active ◽  
Drug Candidate ◽  
One Pot ◽  
Ring Systems ◽  
Drug Candidates ◽  
Fused Ring ◽  
Snar Reaction

Fused-ring systems containing heterocycles are attractive templates for drug discovery. Biologically active 6-5-5+6 fused-ring systems that possess heterocycles are available, but these require a relatively large number of synthetic steps for preparation. Therefore, pyrazolofuropyrazine was designed as a 6-5-5+6 ring system template that incorporates ready accessibility for drug discovery. Pyrazolofuropyrazines were successfully constructed in only a few steps via one-pot SNAr reaction/intramolecular C–H direct arylation. As a drug candidate, pyrazolofuropyrazine has earned a favorable LogP, although significant biological activity has yet to be established; the ready accessibility of pyrazolofuropyrazine template, however, offers an opportunity for the rapid development of promising new drug candidates.

scholarly journals Synthesis of highly substituted 2-spiropiperidines

2018 ◽  
Vol 16 (36) ◽  
pp. 6663-6674 ◽  
Author(s):  
Samuel D. Griggs ◽  
Nathan Thompson ◽  
Daniel T. Tape ◽  
Marie Fabre ◽  
Paul A. Clarke
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
One Pot ◽  
Natural Products Synthesis

Highly substituted novel 2-spiropiperidines, which are scaffolds suitable for drug discovery or natural products synthesis, were synthesized in a simple one-pot or two-pot procedure.

A short de novo synthesis of nucleoside analogs

Science ◽  
2020 ◽  
Vol 369 (6504) ◽  
pp. 725-730 ◽  
Author(s):  
Michael Meanwell ◽  
Steven M. Silverman ◽  
Johannes Lehmann ◽  
Bharanishashank Adluri ◽  
Yang Wang ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Viral Infections ◽  
De Novo ◽  
Nucleoside Analogs ◽  
Aldol Reactions ◽  
Displacement Reaction ◽  
De Novo Synthesis ◽  
One Pot ◽  
Drug Discovery And Development ◽  
Locked Nucleic Acids

Nucleoside analogs are commonly used in the treatment of cancer and viral infections. Their syntheses benefit from decades of research but are often protracted, unamenable to diversification, and reliant on a limited pool of chiral carbohydrate starting materials. We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted acetaldehydes are fluorinated and then directly engaged in enantioselective aldol reactions in a one-pot reaction. A subsequent intramolecular fluoride displacement reaction provides a functionalized nucleoside analog. The versatility of this process is highlighted in multigram syntheses of d- or l-nucleoside analogs, locked nucleic acids, iminonucleosides, and C2′- and C4′-modified nucleoside analogs. This de novo synthesis creates opportunities for the preparation of diversity libraries and will support efforts in both drug discovery and development.

Complex Polycycles from Simple Propargyl Alcohols through Ruthenium-Catalyzed Cascade Reactions and One-Pot Procedures

Synthesis ◽  
2017 ◽  
Vol 50 (04) ◽  
pp. 742-752 ◽  
Author(s):  
Elisabeth Jäckel ◽  
Julia Kaufmann ◽  
Edgar Haak
Keyword(s):  
Drug Discovery ◽  
Organic Synthesis ◽  
High Selectivity ◽  
Multiple Bond ◽  
Cascade Reactions ◽  
Kb Cells ◽  
One Pot ◽  
Bond Forming ◽  
Common Precursor ◽  
Propargyl Alcohols

Multiple bond-forming cascade transformations and one-pot procedures are valuable tools in organic synthesis and drug discovery. These atom-economical processes provide rapid access to natural product-like scaffolds from simple precursors. Herein, we report on ruthenium-catalyzed one-pot conversions of simple 1-alkenyl propargyl alcohols with cyclic 3-ketolactones and dienophiles. Thereby, structurally diverse fused polycycles and functionalized bicyclic structures are accessible from a common precursor with high selectivity. Some of the new drug-like molecules exhibit cytotoxic activity against KB cells.

One Pot Synthesis of Novel Substituted 2',4'-Dihydrospiro[chroman-2,3'-pyrazol]-4- one Derivatives

2018 ◽  
Vol 15 (2) ◽  
pp. 267-274 ◽  
Author(s):  
Venkata S. Tangeti ◽  
Kattaru R. Babu ◽  
Dasari Vasundhara ◽  
K.V.V.V. Satyanarayana ◽  
Himabindu Mylapalli ◽  
...  
Keyword(s):  
Drug Discovery ◽  
13C Nmr ◽  
Building Blocks ◽  
Parallel Synthesis ◽  
Synthetic Route ◽  
One Pot ◽  
Hydrazine Derivatives ◽  
One Pot Synthesis ◽  
Different Types ◽  
The One

Aim and Objective: In the work, we have successfully presented a synthetic route for the synthesis of novel 2',4'-dihydrospiro[chroman-2,3'-pyrazol]-4-one derivatives via one pot multicomponent approach. Materials and Method: Substituted 2',4'-dihydrospiro[chroman-2,3'-pyrazol]-4-one were prepared through cascade three-component condensation of ortho-hydroxyacetophenone, β-ketoester, hydrazine in the presence of pyrrolidine as a catalyst under ethanol reflux conditions. Results: A series of novel 2',4'-dihydrospiro[chroman-2,3'-pyrazol]-4-one have been synthesized through a facile strategy. These structures of newly synthesized derivatives were determined by 1H, 13C NMR, HRMS and CHNS analysis. Conclusion: We have achieved the one-pot, three-component synthesis of highly substituted pyrazole spirochromanones in presence of pyrrolidine as a catalyst under ethanol reflux conditions. Using different types of aliphatic and aromatic β-ketoesters, o-hydroxyacetophenone derivatives and different kinds of hydrazine derivatives as building blocks, we could construct novel libraries of substituted pyrazole spirochromanones that make this method suitable for combinatorial and parallel synthesis in drug discovery.

One-pot four-component synthesis of 4-hydrazinothiazoles: novel scaffolds for drug discovery

2014 ◽  
Vol 55 (40) ◽  
pp. 5465-5467 ◽  
Author(s):  
Sarah Titus ◽  
Kumaran G. Sreejalekshmi
Keyword(s):  
Drug Discovery ◽  
One Pot

scholarly journals Facile Synthesis of 5,6,7,8-tetrahydropyrimido[4,5-d] pyrimidine-2,4 (1H,3H) -dione Analogs via One Pot Multicomponent Reaction

2020 ◽  
Vol 1 (1) ◽  
pp. 1-8
Author(s):  
Shumaila Shafi ◽  
Ammara Chand ◽  
Mehwish Nawaz ◽  
Rashida Parveen ◽  
Saba Munawar ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Multicomponent Reaction ◽  
Heterocyclic Compounds ◽  
Biological Significance ◽  
Biological Properties ◽  
Facile Synthesis ◽  
One Pot ◽  
Conventional Methods ◽  
Work Up

Indeed, MCR technology is widely acknowledged now for its impact on drug discovery projects and is strongly supported by industry as well as academia. Uracil is an important one of the five nucleobases and significantly important because of their biological properties; of which 6-amino uracil is most important and can act as nucleophile and electrophile. 6-Aminouracils being rich are used as starting materials for the synthesis of heterocyclic compounds of biological significance such as pyrido-, pyrazolo, pyrimido and pyrimidines derivatives. 5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione have been synthesized by various conventional methods. However, these methods have drawbacks such as unsatisfactory yields and tedious work-up etc.  In the present work, we would like to report a new route for the synthesis of 5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidine-2,4 (1H,3H)-dione in MCRs.

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