The researchers at the School of Chemistry from the University of Hyderabad (UoH) have recently published their work that has conquered the status of a very important paper in the European Journal of Organic Chemistry
The research team comprises of Swamy Peraka, Badaraita Gorachand, Akram Hussain, Revoju Sravanthi, and Dhevalapally B. Ramachary (corresponding author) *
“This acknowledgement from an esteemed journal like EurJOC is highly commendable and encouraging, says Dr. D B Ramachary”, Professor, School of Chemistry at UoH.
We depend on chemistry for fulfilling our basic needs in our day to day life and hence chemists are continuously thriving to develop methods to synthesize complex molecules like natural products, drugs and other materials with ease. There are many challenges associated with this entire process and one among them is achieving selectivity, chirality or handedness in the synthesized complex natural products. Molecules differ in their spatial arrangement just like the left and right hand of our body. Though both resemble the same, the difference in their spatial arrangement will bring characteristic change in their properties and hence in their application. So in chemistry, it is very important to develop methods to synthesize only one selective spatial isomer among the others, as separation of each of them is tedious.
With the advances in new technologies like asymmetric organocatalysis, chemists are able to effectively mimic nature in synthesizing highly enantioselective or chiral molecules using simple organocatalytic systems in the place of complex enzymatic systems. With the use of this tool, chemists are able to bypass the usage of extremely harmful chemicals and tedious multistep synthetic procedures which often employ usage of high amounts of organic solvents for column purification and therefore making the entire process unendurable.
Organocatalytic asymmetric approach has garnered interest among researchers and is evolving exponentially. This ingenious tool is also acclaimed with a prestigious Nobel Prize in the year 2021. The impact of the usefulness of this tool is witnessed by large growth in the number of their applications in the industry as well as in the academic research field.
The present work is focussed on the one-pot synthesis of octahydro-methanoazulene containing pseudo-natural products, which is found as a basic skeleton in more than 160 natural products, and possessing many interesting biological activities including anti-inflammatory, anti-cancer, anti-tubercular, anti-bacterial, analgesic, anti-malarial, antibiotic, anti-proliferative, and microtubule depolymerisation (see Figure 1). These compounds have been frequently challenged as synthetic targets, due to their demanding architecture and interesting biological activities. Many of these structurally diverse cedranes have been synthesized by using combinations of various reactions like inter-/intramolecular [4+2]-cycloaddition, oxidative dearomatization, [5+2]-cycloaddition, oxidation, ring expansion, acid-catalysed cyclization, alkylation, reduction, intramolecular diazoalkane-carbonyl ring expansion, intramolecular anionic cyclisation, and/or Wittig olefination as key steps in linear or convergent mode.
In the manuscript, the researchers are able to successfully showcase the synthesis of cedranes or pseudo-terpenoid like natural molecules in very good yields with high chemo- and diastereoselectivities and moderate enantioselectivities in a sequential one-pot manner by using a combination of intermolecular olefination, intramolecular Michael and Michael reactions as the key steps from the readily available hydroxy-p-quinone butanals and phosphoranes under the catalytic amounts of natural quinine at ambient temperature for few hours. This is one of the unique one-pot combinations of coupling and annulation routes for the green synthesis of a library of tricyclic pseudo-terpenoids (cedrane scaffolds) with high selectivity and yields.
This one-pot organocatalytic total synthesis of pseudo-natural products will become a sustainable tool for many branches of chemistry, pharma and biology.
Publication Citation: https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202200674
Organocatalytic One-pot Synthesis of Pseudo-Terpenoids
First published:13 June 2022