Late-stage diversification of biologically active pyridazinones via a direct C–H functionalization strategy

2015 ◽  
Vol 13 (2) ◽  
pp. 539-548 ◽  
Author(s):  
Wei Li ◽  
Zhoulong Fan ◽  
Kaijun Geng ◽  
Youjun Xu ◽  
Ao Zhang
Keyword(s):  
Late Stage ◽  
Biologically Active ◽  
Directing Group

Divergent ortho-selective C–H functionalization was successfully established using a pyridazinone moiety as an internal directing group.

Selective C–H Bond Fluorination of Phenols with a Removable Directing Group: Late-Stage Fluorination of 2-Phenoxyl Nicotinate Derivatives

ACS Catalysis ◽  
2015 ◽  
Vol 5 (5) ◽  
pp. 2846-2849 ◽  
Author(s):  
Shao-Jie Lou ◽  
Qi Chen ◽  
Yi-Feng Wang ◽  
Dan-Qian Xu ◽  
Xiao-Hua Du ◽  
...  
Keyword(s):  
Late Stage ◽  
Directing Group

scholarly journals Modular synthesis of α-fluorinated arylmethanes via desulfonylative cross-coupling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Masakazu Nambo ◽  
Jacky C.-H. Yim ◽  
Luiza B. O. Freitas ◽  
Yasuyo Tahara ◽  
Zachary T. Ariki ◽  
...  
Keyword(s):  
Biological Activity ◽  
Late Stage ◽  
Recent Progress ◽  
Cross Coupling ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Arylboronic Acids ◽  
Modular Synthesis ◽  
Synthetic Routes

Abstract α-Fluoromethylarenes are common substructures in pharmaceuticals and agrochemicals, with the introduction of fluorine often resulting in improved biological activity and stability. Despite recent progress, synthetic routes to α-fluorinated diarylmethanes are still rare. Herein we describe the Pd-catalyzed Suzuki-Miyaura cross-coupling of α-fluorinated benzylic triflones with arylboronic acids affording structurally diverse α-fluorinated diarylmethanes. The ease of synthesis of fluorinated triflones as the key starting materials enables powerful late-stage transformations of known biologically active compounds into fluorinated analogs.

Synthetic approaches to [5,6]-benzannulated spiroketal natural products

2011 ◽  
Vol 84 (6) ◽  
pp. 1379-1390 ◽  
Author(s):  
Michael C. McLeod ◽  
Margaret A. Brimble ◽  
Dominea C. K. Rathwell ◽  
Zoe E. Wilson ◽  
Tsz-Ying Yuen
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Electronic Properties ◽  
Late Stage ◽  
Biologically Active ◽  
Formal Synthesis ◽  
Berkelic Acid ◽  
Synthetic Approaches

Studies toward the synthesis of three biologically active [5,6]-benzannulated spiroketal natural products are described. The first total synthesis of paecilospirone is reported, employing a late-stage, pH-neutral spiroketalization. A formal synthesis of γ-rubromycin is described, where the spiroketal moiety is formed by delicate manipulation of the electronic properties of the spirocyclization precursor. Finally, model work toward the total synthesis of berkelic acid is summarized, introducing a novel Horner–Wadsworth–Emmons/oxa-Michael (HWE/oxa-M) cascade to access the spiroketal precursor.

scholarly journals Late-Stage Diversification of Biologically Active Molecules via Chemoenzymatic C–H Functionalization

ACS Catalysis ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 1451-1454 ◽  
Author(s):  
Landon J. Durak ◽  
James T. Payne ◽  
Jared C. Lewis
Keyword(s):  
Late Stage ◽  
Biologically Active

scholarly journals Photooxygenation of an amino-thienopyridone yields a more potent PTP4A3 inhibitor

2016 ◽  
Vol 14 (27) ◽  
pp. 6398-6402 ◽  
Author(s):  
Joseph M. Salamoun ◽  
Kelley E. McQueeney ◽  
Kalyani Patil ◽  
Steven J. Geib ◽  
Elizabeth R. Sharlow ◽  
...  
Keyword(s):  
Late Stage ◽  
Biologically Active

Late-stage photooxygenation can generate novel biologically active lead structures.

scholarly journals Multiple C–H Activation Enabled Modular Construction of Densely Functionalized Sulfur-Contained Arenes

2021 ◽  
Author(s):  
Wensen Ouyang ◽  
Jianhang Rao ◽  
Jie Wang ◽  
Yang Gao ◽  
Yanping Huo ◽  
...  
Keyword(s):  
Biologically Active ◽  
New Drugs ◽  
Advanced Materials ◽  
Synthetic Chemistry ◽  
Modular Construction ◽  
Judicious Choice ◽  
Directing Group ◽  
Synthetic Application ◽  
Molecular Libraries

<div> <p>Modular construction of multiple functionalized arenes from abundant feedstocks, stands as an unremitting pursue goal in synthetic chemistry, which would accelerate the discovery of new drugs an advanced materials. Herein, by using multiple C-H activation strategy, through judicious choice of versatile imidate ester as the key directing group, expedi-ent delivery of molecular libraries of densely functionalized sulfur-contained arenes. Further synthetic application was demonstrated by multiple C-H modification of fused arenes and pharmaceuticals such as Ibuprofen, and concise con-struction of biologically active molecules, Madam dihydrochloride and Bipenamol, was also achieved.</p> </div> <br>

scholarly journals Merging Directed C−H Activations with High-Throughput Experimentation: Development of Predictable Iridium-Catalyzed C−H Aminations Applicable to Late-Stage Functionalization

2021 ◽  
Author(s):  
Erik Weis ◽  
Maria Johansson ◽  
Pernilla Korsgren ◽  
Belén Martín-Matute ◽  
Magnus J Johansson
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
Late Stage ◽  
Functional Group ◽  
Chemical Space ◽  
Material Consumption ◽  
Modern Drug ◽  
High Throughput Experimentation ◽  
Directing Group ◽  
Group Chemical

Herein, we report an iridium-catalyzed directed C−H amination methodology developed using a high-throughput experimentation (HTE)-based strategy, applicable for the needs of automated modern drug discovery. The informer library approach for investigating accessible directing group chemical space for the reaction, in combination with functional group tolerance screening and substrate scope investigations, allowed for the generation of an empirical predictive model to guide future users. Applicability to late-stage functionalization of complex drugs and natural products, in combination with multiple deprotection protocols leading to the desirable aniline matched pairs, serve to demonstrate the utility of the method for drug discovery. Finally reaction miniaturization to a nano molar range highlights the opportunities for more sustainable screening with decreased material consumption.

scholarly journals Peptide late-stage C(sp3)–H arylation by native asparagine assistance without exogenous directing groups

2020 ◽  
Vol 11 (34) ◽  
pp. 9290-9295 ◽  
Author(s):  
Yiyi Weng ◽  
Xingxing Ding ◽  
João C. A. Oliveira ◽  
Xiaobin Xu ◽  
Nikolaos Kaplaneris ◽  
...  
Keyword(s):  
Efficient Method ◽  
Late Stage ◽  
Side Chain ◽  
Directing Group

An efficient method for peptide late-stage C(sp3)-H arylations assisted by unmodified side chain of asparagine (Asn) without any exogenous directing group has been reported.

scholarly journals Late stage iodination of biologically active agents using a one-pot process from aryl amines

RSC Advances ◽  
2017 ◽  
Vol 7 (86) ◽  
pp. 54881-54891 ◽  
Author(s):  
Nikki L. Sloan ◽  
Sajinder K. Luthra ◽  
Graeme McRobbie ◽  
Sally L. Pimlott ◽  
Andrew Sutherland
Keyword(s):  
Late Stage ◽  
Biologically Active ◽  
One Pot ◽  
Aryl Iodide ◽  
Aryl Amines ◽  
Tandem Process

A tandem process has been developed for the general preparation of aryl iodide compounds from anilines that is also applicable for the late-stage iodination of biologically active agents.

scholarly journals Fluorination methods in drug discovery

2016 ◽  
Vol 14 (36) ◽  
pp. 8398-8427 ◽  
Author(s):  
Damian E. Yerien ◽  
Sergio Bonesi ◽  
Al Postigo
Keyword(s):  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Late Stage ◽  
Biologically Active ◽  
Metabolic Degradation

Late stage fluorination methods applied to biologically-active drugs have provided the pharmaceutical industry with new leads that show improved properties such as modulation of lipophilicity, electronegativity, basicity, bioavailability, and deceleration of metabolic degradation.

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