This is the eighth part of the series called `Scientist Says’, where we bring for our readers significant research works of young scientists in various fields.
Dr. Hina Khan started her research journey in year 2014 with Prof. Tushar K. Chakraborty research group, Department of Organic Chemistry, IISc Bangalore. After completing her PhD in July 2019, she worked as a Research Associate in the same lab for a year. In September 2020, she joined a Biocon-group company as a Research Investigator where she worked in collaboration between Bristol Myers Squibb and Syngene International. Currently, she is a postdoctoral fellow at the University of Pittsburgh, United States. She shares her significant research work with Rashida Bakait of India Tomorrow. Here are the excerpts of the interview.
Q. Please briefly explain your research.
Ans. Chemistry is frequently described as the central science and chemical synthesis lies at the heart of the subject. Synthetic organic chemistry underpins several areas of chemistry, including drug discovery, chemical biology, materials science, and engineering. However, the practice of total synthesis of natural products has a rich history of achievements and benefits to science and society that ranges from replicating the molecules of nature in the laboratory to the preparation and production of pharmaceuticals, developing new synthetic strategies and methods, and also synthesizing designed molecules for biology and medicine.
In contributing to the everlasting field of “the art of making molecules”, my research work mainly focuses on the discovery of new organic transformations which are of significant interest to the fields of medicinal chemistry and pharmaceutical development and also uncovering the practical application of Titanocene (III)monochloride in the synthesis of architecturally challenging and biologically important natural products and their inspired synthons.
Q. When did you start and complete your research?
Ans. I started my learning to be a researcher in Aug 2014 with Prof. Tushar K. Chakraborty at IISc, Bangalore, submitted my doctoral thesis in July 2019, and defended the thesis in March 2020. Later in the year 2020, I joined Biocon-group company as a research investigator and worked till April 2021. Currently, I am working as a postdoctoral fellow in University of Pittsburgh, United States.
Q. What was the objective of your research?
Ans. With the ever increasing demand of developing new, efficient, and cheaper methods to construct biologically relevant molecular frameworks, my research aims on the design and developing new synthetic strategies for concise entry to important functionalized bioactive synthetic scaffolds/target.
Q. What were the findings of your research?
Ans. The research findings revolves around two main areas:
I : In developing a synthetic methodology which is flexible and provide single potential route for the diastereoselective construction of diversely substituted 1,3-X,N-heterocyclic variants as valuable scaffolds for natural products and pharmaceuticals, in a diversity-oriented approach. The methodology is amenable for a broad range of substrates based on a metal-free approach.
II. In exploring the synthetic utility of Titanocene(III)monochloride-promoted radical cyclization protocol on to the findings:
a) We have developed a concise and unified approach to gain access to handful iridoid monoterpenes that exhibit wide range of pharmacological activity.
b) We have portrayed a synthetic route to a bicyclic lactone containing a bridgehead hydroxy group, a structure that is present in many natural products of biological and medicinal relevance.
c) Furthermore, an efficient route for the construction of pyrrolo/piperidino[1,2-a]indole derivatives have been developed.
During my research endeavour I have also been involved in the synthesis of sugar amino acid (δ-SAA) based linear lipopeptides (Almiramide analogues) that were screened for their biological activities, viz. antileishmanial and anticancer and the extension of this work is currently active.
Q. What was the conclusion of your research?
Ans. Driven by the ever-increasing demands for small functionalized bioactive scaffolds and the need of broadening the toolbox of unexplored chemical space, our designed strategy provides a flexible route to construct the unique five/six membered 1,3-heterocycles by exploring the synthetic utility of α-phenyl-β-enamino ester following a Mitsunobu-Michael reaction sequence. Next, taking advantage of Cp2Ti(III)Cl-mediated reductive epoxide opening-cyclization, we have developed an expedient and the most concise and unified approach till date in the total synthesis of iridoid monoterpenes in an enantiomerically divergent manner starting from (+)-β-citronellene. Further expansion of the strategy was made to fix hydroxylated bridgehead chiral centre, in the fused/bridged bicyclic lactone, a structure that is present in many natural products of biological and medicinal relevance. Furthermore, as part of our ongoing research interest, we have successfully extended yet another practical application of Ti(III)-mediated epoxide opening-cyclization protocol to devise a simplified route to a pyrrolo/piperido[1,2-a]indole framework, featuring many useful functionalities on the saturated ring, which is ideally suited for further manipulation.
Q. What kind of challenges did you face?
Ans. A doctorate is a long project so your motivation will dip and peak along the way. In multi-step synthesis, designing a synthetic route to the target molecule, optimizing every step of the synthetic plan with the best possible outcome, revising the plan, if needed and starting all-over again is really a burnout process. I would say you can learn more from your failures than successes. They are often catalysts for positive change in the long term. And remember one thing that you are training to be a researcher.
Q. Any scholarships or awards for research?
Ans. For my Ph.D. and Research Associateship (Aug 2014 – Jul 2020), I have received funding from Indian Institute of Science. I have received award for my research work in Indian Peptide symposium, in 2017. Currently, for my postdoctoral program I am receiving scholarship from University of Pittsburgh, United states.
Q. How do you think your research would be beneficial to the industry or society?
Ans. Organic synthesis, the art and science of constructing substances, natural or designed, in the laboratory to replicate the molecules of living creatures, and create other molecules like them, is a remarkable development in human history. Organic synthesis in general, have led to an impressive host of benefits to society, including useful products ranging from pharmaceuticals, dyes, cosmetics and agricultural chemicals to diagnostics and high-technology materials used in computers, mobile phones and spaceships. My research on designing and developing synthetic route to construct heterocycles, terpenoids, alkaloids will provide a new synthetic approach and scope to replicate some of the most intriguing molecules of living nature in the laboratory and apply the developed synthetic strategies to construct variations of them to facilitate biology and medicine.
Q. Any new research you are working on now.
Ans. My current research at University of Pittsburgh, as Post-doctoral fellow is to rationally design and synthesize more efficacious 2-Pralidoxime analogs (2-PAM) which is the only therapeutic countermeasure that is approved by the United States Food and Drug Administration for treating Organophosphorus nerve agents (OPNA) poisoning. However, 2-PAM is not centrally active due to its hydrophilicity and resulting poor blood−brain barrier permeability; hence, these deficiencies warrants the need for antidotes with the development of more hydrophobic analogs.
Q. How do you think your research can be carried forward?
Ans. Taken together, the simplicity and efficiency of the designed strategies can further be adopted to obtain other enticing heterocyclic variants, highly functionalized iridoids/cyclo-pentanoid natural product, also having bridgehead hydroxyl group in a bicyclic lactone, [a]-annulated indole frameworks, which are beneficial to the science of organic synthesis for further innovative applications.
Q. Please give few tips and suggestions to the budding scientists.
Ans. Research is a never-ending journey of learning something new, honing your problem-solving skills and challenging yourself in new ways. I would advise the young scientists to stay curious and stay determined. Science is not easy, become comfortable with failure because a major component of the scientific process is trial and error. Failure is okay! Failing provides some of the biggest learning opportunities and finding new scientific discoveries.
It is not about perfection but curiosity and perseverance. Keep exploring, keep experimenting, keep learning, keep improving. Avoid burnout and look after your mental health to make you more productive in the long run.
Remember to take five-minutes brain break by walking away for a moment, rest that brain and then resume.
