scholarly journals Late stage C–H functionalization via chalcogen and pnictogen salts

2020 ◽  
Vol 11 (37) ◽  
pp. 10047-10060
Author(s):  
Christopher B. Kelly ◽  
Rosaura Padilla-Salinas
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Potential Application ◽  
Medicinal Chemistry

Three unrelated cationic groups, which can replace C–H bonds late stage, have been identified as progenitors to various functional groups. This review discusses the chemistry of these salts and their potential application in medicinal chemistry.

Green chemistry meets medicinal chemistry: a perspective on modern metal-free late-stage functionalization reactions

2021 ◽  
Author(s):  
Juan D. Lasso ◽  
Durbis J. Castillo-Pazos ◽  
Chao-Jun Li
Keyword(s):  
Green Chemistry ◽  
Functional Groups ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Metal Free ◽  
Recent Advances

This review summarizes the most recent advances of metal-free late-stage functionalization (LSF) of pharmaceutically relevant molecules. Particular emphasis is placed on C–H activation as well as the use of endogenous functional groups.

A Practical and General Approach to the Late-Stage Functionalization of Complex Sulfonamides

2019 ◽  
Author(s):  
Patrick Fier ◽  
Kevin M. Maloney
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Building Blocks ◽  
Pharmaceutical Compounds ◽  
Stage Conversion

Herein we describe the development and application of a method for the mild, late-stage conversion of primary sulfonamides to several other other functional groups. These reactions occur via initial reductive deamination of sulfonamides to sulfinates via an NHC-catalyzed reaction of transiently formed <i>N</i>-sulfonylimines. The method described here is tolerant of nearly all common functional groups, as exemplified by the late-stage derivatization of several complex pharmaceutical compounds. Based on the prevalence of sulfonamide-containing drugs and building blocks, we have developed a method to enable sulfonamides to be applied as versatile synthetic handles for synthetic chemsitry.

A Practical and General Approach to the Late-Stage Functionalization of Complex Sulfonamides

2019 ◽  
Author(s):  
Patrick Fier ◽  
Kevin M. Maloney
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Building Blocks ◽  
Pharmaceutical Compounds ◽  
Stage Conversion

Herein we describe the development and application of a method for the mild, late-stage conversion of primary sulfonamides to several other other functional groups. These reactions occur via initial reductive deamination of sulfonamides to sulfinates via an NHC-catalyzed reaction of transiently formed <i>N</i>-sulfonylimines. The method described here is tolerant of nearly all common functional groups, as exemplified by the late-stage derivatization of several complex pharmaceutical compounds. Based on the prevalence of sulfonamide-containing drugs and building blocks, we have developed a method to enable sulfonamides to be applied as versatile synthetic handles for synthetic chemsitry.

A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

2019 ◽  
Author(s):  
Victor Bloemendal ◽  
Floris P. J. T. Rutjes ◽  
Thomas J. Boltje ◽  
Daan Sondag ◽  
Hidde Elferink ◽  
...  
Keyword(s):  
Biological Activity ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Cross Coupling ◽  
Modular Approach ◽  
Coupling Reactions ◽  
One Pot ◽  
Biologically Relevant ◽  
Cross Coupling Reactions ◽  
Chemistry Research

<p>In this manuscript we describe a modular pathway to synthesize biologically relevant (–)-<i>trans</i>-Δ<sup>8</sup>-THC derivatives, which can be used to modulate the pharmacologically important CB<sub>1</sub> and CB<sub>2</sub> receptors. This pathway involves a one-pot Friedel-Crafts alkylation/cyclization protocol, followed by Suzuki-Miyaura cross-coupling reactions and gives rise to a series of new Δ<sup>8</sup>-THC derivatives. In addition, we demonstrate using extensive NMR evidence that similar halide-substituted Friedel-Crafts alkylation/cyclization products in previous articles were wrongly assigned as the para-isomers, which also has consequence for the assignment of the subsequent cross-coupled products and interpretation of their biological activity. </p> <p>Considering the importance of the availability of THC derivatives in medicinal chemistry research and the fact that previously synthesized compounds were wrongly assigned, we feel this research is describing a straightforward pathway into new cannabinoids.</p>

Reductive Cleavage of Secondary Sulfonamides: Converting Terminal Functional Groups into Versatile Synthetic Handles

2019 ◽  
Author(s):  
Patrick Fier ◽  
Suhong Kim ◽  
Kevin M. Maloney
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Reductive Cleavage ◽  
Bioactive Molecules ◽  
General Method

Sulfonamides are pervasive in drugs and agrochemicals, yet are typically considered as terminal functional groups rather than synthetic handles. To enable the general late-stage functionalization of secondary sulfonamides, we have developed a mild and general method to reductively cleave the N-S bonds of sulfonamides to generate sulfinates and amines, components which can further react <i>in-situ</i> to access a variety of other medicinally relevant functional groups. The utility of this platform is highlighted by the selective manipulation of several complex bioactive molecules.

scholarly journals Unified Template Strategy for Editing Multiple Remote C–H Bonds

2021 ◽  
Author(s):  
Zhoulong Fan ◽  
Xiangyang Chen ◽  
Keita Tanaka ◽  
Han Seul Park ◽  
Nelson Y. S. Lam ◽  
...  
Keyword(s):  
Late Stage ◽  
Medicinal Chemistry ◽  
Careful Consideration ◽  
Geometric Parameters ◽  
Complementary Methods ◽  
Rapid Access ◽  
Aza Arenes

Through consecutive selective C–H functionalization at multiple sites, the direct molecular editing of heteroarene carbon-hydrogen (C–H) bonds has the potential to grant rapid access into diverse molecular space; a valuable but often challenging venture to achieve in medicinal chemistry. Contrasting with electronically-biased heterocyclic C–H bonds, remote benzocyclic C–H bonds on bicyclic aza-arenes are especially difficult to differentiate due to lack of intrinsic steric/electronic biases. Through careful consideration of distance and geometric parameters, we herein report a unified catalytic directing template strategy that enables the modular functionalization of chemically-similar and adjacent remote positions on bicyclic aza-arene scaffolds. Differentiated by using two structurally distinct catalytic directing templates, this method enables direct C–H olefination, alkynylation, and allylation at previously inaccessible C6 and C7 positions of quinolines, and is amenable to the iterative, modular, and late-stage C–H editing of quinoline-containing pharmacophores and pharmaceuticals. This report, in combination with our previous C5-selective template and other complementary methods, now fully establishes a unified ‘molecular editing’ strategy to directly modify aza-arene heterocycles at any given site.

scholarly journals A Single-Step Synthesis of Azetidine-3-Amines

2020 ◽  
Author(s):  
Brian J Wang ◽  
Matthew Duncton
Keyword(s):  
Functional Groups ◽  
Late Stage ◽  
Single Step ◽  
Secondary Amines ◽  
High Yield ◽  
Primary Amines ◽  
Privileged Structure ◽  
One Step ◽  
Alternative Procedures ◽  
Approved Drugs

<div> <p>The azetidine group is frequently encountered within contemporary medicinal chemistry where it is viewed as a privileged structure. However, the introduction of an azetidine can be synthetically challenging. Herein, a straight-forward one step synthesis of azetidine-3-amines, starting from a bench stable, commercial material is presented. The reaction tolerates functional groups commonly encountered in biological-, medicinal- and agro-chemistry, and proceeds in moderate-to-high yield with secondary amines, and moderate-to-low yield with primary amines. The methodology compares favorably to recent alternative procedures and can be utilized in “any-stage” functionalization, including late-stage azetidinylation of approved drugs and other compounds with pharmacological activity.</p> </div>

scholarly journals Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2783 ◽  
Author(s):  
Shu-Guang Zhang ◽  
Chao-Gen Liang ◽  
Wei-Hua Zhang
Keyword(s):  
Functional Groups ◽  
Medicinal Chemistry ◽  
Biological Activities ◽  
Drug Molecules ◽  
Recent Advances

Indazole-containing derivatives represent one of the most important heterocycles in drug molecules. Diversely substituted indazole derivatives bear a variety of functional groups and display versatile biological activities; hence, they have gained considerable attention in the field of medicinal chemistry. This review aims to summarize the recent advances in various methods for the synthesis of indazole derivatives. The current developments in the biological activities of indazole-based compounds are also presented.

scholarly journals Tyrosine and Drug-like Late-stage Benzylic Functionalization via Photoredox Catalysis

2020 ◽  
Author(s):  
Tobias Brandhofer ◽  
Volker Derdau ◽  
María Mendez ◽  
Christoph Pöverlein ◽  
Olga Garcia Mancheno
Keyword(s):  
Natural Products ◽  
Visible Light ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Functional Group ◽  
Reaction Conditions ◽  
Site Selectivity ◽  
Wide Range ◽  
High Yields ◽  
Therapeutic Compounds

Abstract Visible light mediated late-stage functionalization is a rising field in synthetic and medicinal chemistry, allowing the fast and diversified modification of valuable, potentially therapeutic compounds such as peptides. However, there are relatively few mild methodologies for the C(sp3)-H functionalization of complex peptides. Herein, we report a visible light mediated photocatalytic protocol for the benzylic C-H modification of tyrosine and related C-H bonds. The embraced radical-cation/deprotonation strategy enables an incorporation of a wide range of valuable functional groups in high yields and chemoselectivity. The mild reaction conditions, site-selectivity and high functional group tolerance was highlighted by the functionalization of complex peptides, drugs and natural products, providing a promising synthetic platform in medicinal chemistry.

scholarly journals Pharmacological and Medicinal Chemistry Aspects of Cannabis Compounds

2011 ◽  
Vol 6 (2) ◽  
pp. 16-18
Author(s):  
T. Cotelea
Keyword(s):  
Chemical Analysis ◽  
Functional Groups ◽  
Medicinal Chemistry ◽  
Spatial Arrangement ◽  
Pharmacological Action ◽  
Scientific Interest ◽  
General Overview

The current communication includes a general overview of the scientific interest and medicianl chemistry aspects of Cannabis compounds. It relates to metabolism, pharmacological action and phisico-chemical analysis of these compounds, as well as of some isomers differing in spatial arrangement of functional groups.

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