scholarly journals Modular ketal-linked prodrugs and biomaterials enabled by organocatalytic transisopropenylation of alcohols

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Na Yu ◽  
Yang Xu ◽  
Tao Liu ◽  
Haiping Zhong ◽  
Zunkai Xu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Small Molecule ◽  
Functional Group ◽  
Building Blocks ◽  
Hydroxyl Group ◽  
Reaction Conditions ◽  
Small Molecule Drugs ◽  
Wide Range ◽  
Scalable Synthesis ◽  
Traditional Approaches

AbstractIsopropenyl ethers are critical intermediates for accessing medicinally valuable ketal-based prodrugs and biomaterials, but traditional approaches for the synthesis of isopropenyl ethers suffer from poor functional group compatibility and harsh reaction conditions. Here, we develop an organocatalytic transisopropenylation approach to solve these challenges, enabling the synthesis of isopropenyl ethers from various hydroxyl-group-containing small-molecule drugs, polymers, and functional building blocks. The method provides a straightforward and versatile synthesis of isopropenyl ethers, features excellent tolerance of diverse functional groups, applies to a wide range of substrates, and allows scalable synthesis. The development of this organocatalytic transisopropenylation approach enables access to modular preparation of various acid-sensitive ketal-linked prodrugs and functionalized ketalated biomaterials. We expect our syntheses and transformations of isopropenyl ethers will find utility in several diverse fields, including medicinal chemistry, drug delivery, and biomaterials.

scholarly journals A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

2019 ◽  
Vol 15 ◽  
pp. 1523-1533 ◽  
Author(s):  
András György Németh ◽  
György Miklós Keserű ◽  
Péter Ábrányi-Balogh
Keyword(s):  
Elemental Sulfur ◽  
Building Blocks ◽  
Reaction Conditions ◽  
One Pot ◽  
Catalyst Free ◽  
Synthetic Procedure ◽  
Three Component Reaction ◽  
Wide Range ◽  
Organic Chemist ◽  
The One

A new multicomponent reaction has been developed between isocyanides, sulfur and alcohols or thiols under mild reaction conditions to afford O-thiocarbamates and dithiocarbamates in moderate to good yields. The one-pot reaction cascade involves the formation of an isothiocyanate intermediate, thus a catalyst-free synthesis of isothiocyanates, as valuable building blocks from isocyanides and sulfur is proposed, as well. The synthetic procedure suits the demand of a modern organic chemist, as it tolerates a wide range of functional groups, it is atom economic and easily scalable.

Matrix metalloproteinase-sensitive hydrogel microparticles for pulmonary drug delivery of small molecule drugs or proteins

2015 ◽  
Vol 3 (27) ◽  
pp. 5629-5634 ◽  
Author(s):  
Emilie Secret ◽  
Kelsey E. Crannell ◽  
Stefan J. Kelly ◽  
Maria Villancio-Wolter ◽  
Jennifer S. Andrew
Keyword(s):  
Drug Delivery ◽  
Matrix Metalloproteinases ◽  
Matrix Metalloproteinase ◽  
Small Molecule ◽  
Pulmonary Drug Delivery ◽  
Hydrogel Microparticles ◽  
Small Molecule Drugs

Hydrogel microparticles sensitive to matrix metalloproteinases are studied for release of drugs and proteins into the lungs.

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.

Cu-Catalyzed Allylation of Amines with Cyclopropyldiphenylsulfonium Trifluoromethanesulfonate

Synthesis ◽  
2022 ◽  
Author(s):  
Yu Ma ◽  
Ze-Yu Tian ◽  
Shuang-Yang Zheng ◽  
Cheng-Pan Zhang
Keyword(s):  
Aromatic Amines ◽  
Functional Group ◽  
Secondary Amines ◽  
Reaction Conditions ◽  
Drug Molecules ◽  
Wide Range ◽  
Catalyzed Reactions ◽  
Cyclic Compounds

Cyclopropyldiphenylsulfonium salt is a famous ylide precursor that was previously extensively employed in the preparation of cyclic compounds and has been successfully utilized as an efficient allylation reagent in this work. The Cu-catalyzed reactions of cyclopropyldiphenylsulfonium trifluoromethanesulfonate with amines in the presence of an appropriate ligand provided the N-allylated products in good yields. Aliphatic/aromatic amines and primary/secondary amines were all mildly converted under the reaction conditions. This protocol was also applicable to N-functionalization of drug molecules, supplying the corresponding N-allylated compounds in satisfactory yields. The reaction showed good functional group tolerance, a wide range of substrates, and excellent chemoselectivity, which offered an interesting method for the synthesis of N-allyl amines.

Arylene–ethynylene macrocycles: Privileged shape-persistent building blocks for organic materials

2012 ◽  
Vol 84 (4) ◽  
pp. 869-878 ◽  
Author(s):  
Dustin E. Gross ◽  
Ling Zang ◽  
Jeffrey S. Moore
Keyword(s):  
Functional Group ◽  
Organic Materials ◽  
Building Blocks ◽  
Alkyne Metathesis ◽  
Reaction Conditions ◽  
Traditional Methods ◽  
Dynamic Covalent Chemistry ◽  
Highly Active ◽  
Recent Advances ◽  
Metathesis Catalyst

This report details the advances in synthetic strategies toward arylene–ethynylene macrocycles (AEMs). After a brief description of traditional methods, we summarize recent advances based on dynamic covalent chemistry (DCC) whereby a highly active and functional group tolerant alkyne metathesis catalyst yields scalable quantities of AEMs under thermodynamic controlled reaction conditions.

Synthesis of 6-Alkynyl-6-hydroxyindoloquinazolinone Scaffolds via Copper-Catalyzed Alkynylation of Tryptanthrins

Synlett ◽  
2021 ◽  
Author(s):  
Yu Guo ◽  
Ebrahim-Alkhalil M. A. Ahmed ◽  
Hongxin Liu ◽  
Xinhua Li ◽  
Juan Li ◽  
...  
Keyword(s):  
Functional Group ◽  
Building Blocks ◽  
Sonogashira Coupling ◽  
Terminal Alkynes ◽  
Reaction Conditions

We report a copper catalyzed direct alkynylation reaction of tryptanthrins with terminal alkynes under mild reaction conditions. The developed method provides an array of synthetic building blocks of 6-alkynyl-6-hydroxyindoloquinazolinone compounds in moderate to good yields with varied functional group compatibility. Furthermore, the obtained adducts can be smoothly converted into versatile building blocks via hydrogenation, hydration and further Sonogashira coupling transformations.

scholarly journals Modification of Alginates to Modulate Their Physic-Chemical Properties and Obtain Biomaterials with Different Functional Properties

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7264
Author(s):  
Piotr Rosiak ◽  
Ilona Latanska ◽  
Paulina Paul ◽  
Witold Sujka ◽  
Beata Kolesinska
Keyword(s):  
Drug Delivery ◽  
Regenerative Medicine ◽  
Literature Review ◽  
Functional Properties ◽  
Synthetic Peptides ◽  
Chemical Properties ◽  
Biological Properties ◽  
Biologically Active ◽  
Reaction Conditions ◽  
Wide Range

Modified alginates have a wide range of applications, including in the manufacture of dressings and scaffolds used for regenerative medicine, in systems for selective drug delivery, and as hydrogel materials. This literature review discusses the methods used to modify alginates and obtain materials with new or improved functional properties. It discusses the diverse biological and functional activity of alginates. It presents methods of modification that utilize both natural and synthetic peptides, and describes their influence on the biological properties of the alginates. The success of functionalization depends on the reaction conditions being sufficient to guarantee the desired transformations and provide modified alginates with new desirable properties, but mild enough to prevent degradation of the alginates. This review is a literature description of efficient methods of alginate functionalization using biologically active ligands. Particular attention was paid to methods of alginate functionalization with peptides, because the combination of the properties of alginates and peptides leads to the obtaining of conjugates with properties resulting from both components as well as a completely new, different functionality.

scholarly journals Metal-Free Photoredox Phosphonation of C–N and C–X Bonds in Aqueous Solvent Mixtures

2021 ◽  
Author(s):  
Lei Pan ◽  
Alexandra Kelley ◽  
Maria Victoria Cooke ◽  
Macy Deckert ◽  
Sébastien Laulhé
Keyword(s):  
Building Blocks ◽  
Solvent Mixture ◽  
Solvent Mixtures ◽  
Environmental Footprint ◽  
Reaction Conditions ◽  
Metal Free ◽  
Aqueous Solvent ◽  
Wide Range ◽  
Reaction Proceeds ◽  
Phosphonate Esters

Aryl phosphonate esters are valuable moieties for the pharmaceutical and agrochemical industries. Accessing such compounds from affordable and abundant phosphite reagents and a wide range of aromatic building blocks under metal-free, visible light-induced reaction conditions would represent a desirable technology. Herein, we present an efficient and mild methodology for the synthesis of aromatic phosphonate esters in good to excellent yields using DBU and phenothiazine as a photoredox catalyst. The reaction exhibits wide functional group compatibility enabling the transformation in presence of ketone, amide, ester, amine, and alcohol moieties. Importantly, the reaction proceeds using a green solvent mixture primarily composed of water, thus lowering the environmental footprint of this transformation compared to current methods.

Synthesis of silodosin glucuronide and its deuterated counterpart: solving a problematic O-glycosylation of a nitrogen-containing molecule

2017 ◽  
Vol 23 (3) ◽  
pp. 187-195
Author(s):  
Jun Zhou ◽  
Yunpeng Liu ◽  
Hailiang Zhu ◽  
He Zhu ◽  
Peng George Wang
Keyword(s):  
Hydrogen Bond ◽  
Chemical Synthesis ◽  
Small Molecule ◽  
Acyl Migration ◽  
Complex Mixture ◽  
Side Reactions ◽  
Reaction Conditions ◽  
Adrenoceptor Antagonist ◽  
Small Molecule Drugs ◽  
Sequential Addition

AbstractWe report here the first chemical synthesis of silodosin glucuronide, a metabolite of the α1A-adrenoceptor antagonist silodosin, and its deuterium-labeled counterpart. As a key synthetic step, the incorporation of a glucuronosyl unit onto silodosin invariably led to either an undesired orthoester or a complex mixture under an array of standard glycosylation conditions. This problematic O-glycosylation may be attributed to the presence of multiple basic groups that could neutralize the acidic activators, decrease the nucleophilicity of a hydroxy group via hydrogen bond or even facilitate acyl migration side reactions. After elaborate tuning of reaction conditions, success was eventually achieved by using perbenzoylated d-glucuronosyl N-phenyltrifluroacetimidate (PTFA) as donor in combination with a procedure of sequential addition of TMSOTf. This protocol is potentially general for the glycosylation of other nitrogen-containing small molecule drugs.

Self-assembling peptide-based nanodrug delivery systems

2019 ◽  
Vol 7 (12) ◽  
pp. 4888-4911 ◽  
Author(s):  
Qian Wang ◽  
Nan Jiang ◽  
Bo Fu ◽  
Fan Huang ◽  
Jianfeng Liu
Keyword(s):  
Drug Delivery ◽  
Small Molecule ◽  
Delivery Systems ◽  
Present Review ◽  
Peptide Conjugates ◽  
Nanodrug Delivery ◽  
Self Assembling ◽  
Small Molecule Drugs ◽  
Delivery Strategies

The present review outlines the methods designing self-assembling peptide-based NDDs for small molecule drugs, with an emphasis on the different drug delivery strategies and their applications in using peptides and peptide conjugates.

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