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Krishna P Kaliappan was born in Kallidaikurichi, a small town in Tirunelveli District of Tamil Nadu. He is the youngest in his family of seven children. He completed his primary school in STC and higher secondary education from Tilak Vidyalaya Higher Secondary School in Kallidaikurichi. He did his B.Sc (Chemistry) from Thiruvalluvar College, Papanasam in 1985 and moved to School of Chemistry, Madurai Kamaraj University for his Masters in Chemistry. He received the Gold medal for standing first in M.Sc Chemistry at Madurai Kamaraj University in 1990. He was one among the top 6 candidates at the National level examination conducted by CSIR/UGC for JRF in 1991.

He joined Indian Institute of Science, Bangalore for his Ph.D in 1990, in Organic Chemistry. He worked on the total synthesis of small natural products using Birch reduction and Diels-Alder reaction as key reactions. Later, he moved to University of Geneva in early 1997 for his first post-doc and worked with Prof. Peter E. Kundig. After spending a couple of years at Geneva, he moved transatlantic to Duke University to work with Prof. Michael Pirrung for his second post-doc.

In April 2001, he returned to India and joined Indian Institute of Technology Bombay as Assistant Professor where he is currently a full Professor since February 2009. He is currently serving as the first Dean (Strategy) of IIT Bombay from August 2022. Earlier he had served as the Dean of Faculty Affairs, IIT Bombay (May 2018-May 2021), Associate Dean (R&D), IIT Bombay (Oct-2012-Dec 2015) and also as Chair of Department of Chemistry, IIT Bombay (Jan 2016-April 2018).

He was Institute Chair Professor from 2014-2021. He briefly served as a Juliot Visiting Professor at ESPCI, Paris and Visiting Professor at UMASS Amherst. He served as one of the Editorial Advisory Board members of Organic and Biomolecular Chemistry Journal (2013-2021) and Chemistry An Asian Journal (2014-21). He is an elected Fellow of Indian Academy of Sciences (FASc) since 2016 and Fellow of Royal Society of Chemistry (FRSC) since 2008. He was the organising Chairman of ICOS 21 (21st International Conference on Organic Synthesis) held at IIT Bombay in 2016.

His research program at IIT Bombay mainly revolves around organic synthesis, especially on total synthesis of complex natural products. He has guided 26 PhD students and 36 MSc students so far. Currently, 16 PhD students, 2 MSc students and 1 post-doc are working in his laboratory.

He has received several awards, notably Prof. C. N. R. Rao National Prize in Chemical Sciences, Excellence in Teaching Award from IIT Bombay, Prof. S. C. Bhattacharya award for Excellence in Research in Pure Sciences at IIT Bombay, Swarnajayanti Fellowship and B. M. Birla Science award. One of his Ph.D students, Dr. Parthasarathi Subramanian, is currently a faculty at IIT Kanpur and many of his former co-workers are serving Pharma/Agro/Oil companies in India/abroad.