General Synthesis of Unsymmetrical 3,3'-(Aza)diindolylmethane Derivatives

The Journal of Organic Chemistry
Thanigaimalai PillaiyarChrista E Müller

Abstract

Diindolylmethane (DIM) and its derivatives have recently been in the focus of interest due to their significant biological activities, specifically in cancer prevention and therapy. Molecular targets of DIM have been identified, e.g., the immunostimulatory G protein-coupled receptor GPR84. However, most of the reported and investigated DIM derivatives are symmetrical because general methods for obtaining unsymmetrical DIMs have been lacking. To optimize the interaction of DIM derivatives with their protein targets, unsymmetrical substitution is required. In the present study we developed a new, mild and efficient access to unsymmetrically substituted 3,3'-DIMs by reaction of (3-indolylmethyl)trimethylammonium iodides with a wide range of substituted indole derivatives. 7-Azaindole also led to the 3,3'-connected DIM analogue, while 4- and 5-azaindoles reacted at the N1-nitrogen atom as confirmed by X-ray crystallography. The reactions were performed in water without the requirement of a catalyst or other additives. Wide substrate scope, operational simplicity, environmentally benign workup, and high yields are further advantages of the new method. The synthetic protocol proved to be suitable for upscaling to yield gram amounts f...Continue Reading

References

Nov 11, 2003·Life Sciences·Shigeki TakedaTatsuya Haga
Nov 25, 2003·Current Opinion in Otolaryngology & Head and Neck Surgery·Brian J Wiatrak
Feb 20, 2007·Organic Letters·Gabriela de la HerranAurelio G Csákÿ
Dec 25, 2007·The Journal of Nutrition·Han Jin ChoJung Han Yoon Park
Nov 27, 2009·Gynecologic Oncology·Giuseppe Del PrioreAlan A Arslan
Jan 1, 2010·Chemical Reviews·Morteza ShiriZahra Tanbakouchian
May 18, 2012·Journal of Experimental & Clinical Cancer Research : CR·Xiao-Fei YinMin-Hu Chen
Apr 10, 2014·Journal of Physiology and Biochemistry·Poornima JayakumarMirunalini Sankaran
Apr 7, 2016·Chemical Communications : Chem Comm·K DevarajL T Pilarski
Jul 29, 2016·The Journal of Biological Chemistry·Janis J FüllerJürgen Moser
Apr 14, 2017·Journal of Medicinal Chemistry·Thanigaimalai PillaiyarChrista E Müller

❮ Previous
Next ❯

Citations

Mar 5, 2019·Chemistry : a European Journal·Ze-Kun YangMasanobu Uchiyama
Jul 6, 2021·Beilstein Journal of Organic Chemistry·Thanigaimalai PillaiyarChrista E Müller
Jul 31, 2021·Scientific Reports·Beata JasiewiczLucyna Mrówczyńska
Aug 25, 2021·Organic Letters·Guozhe GuoCongde Huo
Oct 19, 2021·ACS Pharmacology & Translational Science·Laura JenkinsGraeme Milligan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.