For some selected compounds already prepared on a lab-scale, the corresponding procedures appropriate for their scale-up to the pre-pilot (kilogram) levels have been carefully executed; this is highly critical to reflect the practicability of the developed protocols and serves as a bridge to further translate them from the laboratory to the industry. Selection of a synthetic route must accommodate methods of purification which, towards the industrial applications, involve either crystallization for solid or distillation for liquid with minimal, if any, column chromatography. Other equipment necessary for the separation of organic- and aqueous-soluble layers is also vital. Moreover, appropriate analytical instruments such as high-performance liquid chromatography (HPLC) to follow the progress of the reaction must accommodate the real-time analysis. During the COVID-19 pandemic, our laboratory has successfully upscaled the preparation of the anti-viral drug molnupiravir starting from cytidine. Two synthetic routes—one using only chemicals and the other using immobilized lipase—have been successfully executed to furnish the desired product in only 2-3 steps in comparable overall yields on the kilogram scales. Using enzyme as a biocatalyst also conforms to the Thai government policy on the bio-circular-green economy (BCG) for sustainable development. This is an important step forward to establish the requisite process chemistry in Thailand for producing APIs on larger scales.

Structure-activity relationships (SARs) are keys to the success of drug discovery and development programs as they provide the pivotal link between structural modifications and desirable biological activities. To this end, viable synthetic strategies must be robust and accommodate a wide range of functional group installations at various stages to generate libraries of candidates with sufficiently explored chemical spaces. Detailed molecular mechanisms of biological actions have been performed to shed some light on understanding the interactions between the molecular target and ligands. Similar to modern drug discovery programs, toxicological profiling has been integrated at an early stage to enhance the success rate of advancing these drug-like candidates to further stages of drug discovery and development process.

      The advent of hardware with powerful computing capability and software with multifaceted applications for chemistry has enabled the more accurate identification of the discrete stereo- and regio-chemical issues of plausible structures with greater certainty and efficiency. The process encompasses the spectroscopic data of the compounds in question and statistical analysis of the possible structures to delineate the true compound identity. In addition, relevant reaction coordinate parameters and experimentally obtained data (e.g., kinetic, physical as well as spectroscopic) can be utilized to distinguish plausible reaction pathways, thereby determining the reaction mechanism. Knowledge from computational chemistry can be utilized as a guide to design or improve the reactions which may deliver the desired products in higher yields, with better stereoselectivities, regioselectivities, and chemical selectivity.

Challenges in total synthesis of natural products lie in the disconnection and execution of series of chemical reactions. Ingenious insights and capability to exploit and manipulate available repertoire of chemical methods as well as subtle differences in chemical reactivities are crucial for the successfully designed synthetic approaches with highest efficiency. In addition, utility of biomimetic/bio-inspired syntheses has also been illustrated. Stereochemical outcomes of each step for those containing stereogenic centers are important considerations upon devising synthetic routes. Divergent synthesis has also played an important role in designing a synthetic strategy to a common intermediate for the preparation of other analogs, thus increasing the efficiency and flexibility of such developed route. State-of-the-art synthetic approaches for various cores of natural products have been designed and executed successfully. Over the years, our laboratory has prepared both plant- and marine-derived natural products and their analogs including: lamellarins/azalamellarins, (±)-palodesangrens, (±)-paucifloral F, negundin A, (+)-ζ-clausenamide, (+)-balasubramide, cannabinol, isocryptolepine, (±)crispine A, (+)-phenanthroindolizidine, (+)-phenanthroquinolizidine, (±)-seco-antofine, (±)-julandine, lophocladines, (±)-castanospermine, (+)-8-aminolentiginosine, and (-)-epi-epiquinamide.

Developing novel and efficient synthetic methods play vital roles in advancing organic synthesis to access privileged scaffolds. Not only has catalysis been a cornerstone for developing various methods and the protocols with less impact or footprint on the environment also deemed absolutely necessary for sustainability. Novel chemistries have been devised on the basis of green chemistry principles such as the use of water as a solvent, solid-supported chemicals as reagent, and microwave/electricity/light as alternative and renewable sources of energy. Modern practices on organic synthesis have been employed to the fullest potential, spanning from the chemo-, regio-, and stereo-selective processes to the cyclization of multi-ring systems. Annulation of different ring sizes as well as installation of chemically unique functional groups have been successfully achieved via these considerations. Developing these synthetic methods has enabled our laboratory to advance the frontier in organic synthesis to discover the untapped areas of research. New chemical reactivities of various reactive intermediates have been revealed, many of which are unprecedented. Transition-metal catalysis such as Pd, Pt, Ag, Ru, Cu, Ni, and Ir has been exploited to affect novel bond formations.

Name : Miss Bunkuea Chantrathonkul (Research Assistant) Office Address : Room : 1704 CGI Laboratory of Medicinal Chemistry 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel : +66 2554 1900 (ext. 2727) Email : [email protected] Research Interests Biological activities Small molecule compounds Drug-like compounds Education 1995-1999 B.A. Apply Biology, Suan Sunandha Institute, Thanland Work Experiences 2004 – present Research Assistant, Chulabhorn Research Institute, Thailand Publications Selected Publications Sopha P, Phutubtim N, Chantrathonkul B, Ploypradith P, Ruchirawat S,Chittchang M. Roles of autophagy in relation to mitochondrial stress responses of HeLa cells to lamellarin cytotoxicity. Toxicology. 2021;462:152963. Other Publications Intaramat A, Sornprachum T, Chantrathonkul B, Chaisuriya P, Jongruja N, Kumsang Y, Sandee A, Santurio J, Grooters A, Ratanabanangkoon K. Protein A/G-based immunochromatographic test for serodiagnosis of pythiosis in human and animal subjects from Asia and Americas. Med Mycol. 2016;54(6):641-7. Ratanabanangkoon K*, Simsiriwong P, Pruksaphon K, Tan K, Eursakun S, Tan C, Chantrathonkul B, Wongwadhunyoo W, Youngchim S, Tan N. A novel in vitro potency assay of antisera against Thai Naja kaouthia based on nicotinic acetylcholine receptor binding. Sci Rep. 2017;7(1):8575. Ratanabanangkoon K*, Simsiriwong P, Pruksaphon K, Tan K, Chantrathonkul B, Eursakun S, Tan C. An in vitro potency assay using nicotinic acetylcholine receptor binding works well with antivenoms against Bungarus candidus and Naja naja. Sci Rep. 2018;8:9716.

Name : Dr. Aurapat Ngamnithiporn (Research Scientist) Office Address : Room : R413 / R403A Laboratory of Medicinal Chemistry 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel : +66 2553 8555 (ext. 3042) Email : [email protected] Research Interests Synthetic methodology Asymmetric catalysis Total synthesis of natural products Education 2018 – 2021 Ph.D Organic Chemistry, California Institute of Technology, U.S.A. 2015 – 2018 M.Sc. Organic Chemistry, California Institute of Technology, U.S.A. 2011 – 2015 B.A. Chemistry, Magna cum laude, Carleton College, U.S.A. Work Experiences 2021 – present Research Scientist, Chulabhorn Research Institute, Thailand Awards 2010 – 2021 Royal Thai Government Scholarship 2015 ACS Undergraduate Award in Organic Chemistry, U.S.A. 2015 Sigma Xi Undergraduate Research Award, Carleton College, U.S.A. 2015 Richard Ramette Teaching Award, Carleton College, U.S.A. 2015 Phi Beta Kappa National Honor Society, Carleton College, U.S.A. 2015 Jerry Mohrig Prize in Chemistry, Carleton College, U.S.A. Publications Selected Publications Ngamnithiporn, A.; Chuentragool, P.; Ploypradith, P.; Ruchirawat, S. Syntheses of 3-Aryl Tetrahydroisoquinolines via an Intermolecular [4 + 2] Cycloaddition of Sultines with Imines. Org. Lett. 2022, 24, 4192–4196. Kim, A. N.; Ngamnithiporn, A.; Bartberger, M. D.; Stoltz, B. M. Iridium-Catalyzed Asymmetric Trans-Selective Hydrogenation of 1,3-Disubstituted Isoquinolines. Chem. Sci. 2022, 13, 3227–3232. Kim, A. N.;* Ngamnithiporn, A.;* Welin, E. R.; Daiger, M. T., Grunanger, C. U.; Bartberger, M. D.;...

Name : Dr. Sakunchai Khumsubdee (Research Scientist) Office Address : Room : R512 / R403A Laboratory of Medicinal Chemistry 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel : +66 2553 8555 (ext. 3048) Email : [email protected] Research Interests Synthetic methodology Organometallic catalysis Biological active metal synthesis Education 2015 – 2017 Postdoc Organic Chemistry, Massachusetts Institute of Technology, U.S.A. 2007 – 2013 Ph.D Organic Chemistry, Texas A&M University, U.S.A. 2002 – 2006 B.A. Chemistry, Mahidol University, THAILAND Work Experiences 2014 – present Research Scientist, Chulabhorn Research Institute, Thailand Awards 2007 – 2013 Royal Thai Government Scholarship 2002 – 2006 Sritrang Thong Scholarship, Mahidol University, THAILAND Publications Selected Publications Thongararm, P.; Fedeles, B. I.; Khumsubdee, S.; Armijo, A. L.; Kim, L.; Thiantanawat, A.; Promvijit, J.; Navasumrit, P.; Ruchirawat, M.; Croy, R. G.; Essigmann, J. M.* Modulation of N-Methyl-N-nitrosourea Mutagenesis in Mouse Embryo Fibroblasts Derived from the gpt Delta Mouse by an Inhibitor of the O6-Methylguanine Methyltransferase, MGMT. Chem. Res. Toxicol. 2020, 33, 625-633. Khumsubdee, S.; Burgess, K.* Metathesis for catalyst design: metacatalysis. Tetrahedron 2014, 70, 1326-1335. Khumsubdee, S.; Zhou, H.; Burgess, K.* Homo-Roche Ester Derivatives by Asymmetric Hydrogenation and Organocatalysis. J. Org. Chem. 2013, 78, 11948-11955. Khumsubdee, S.; Fan, Y.; Burgess, K.* A Comparison between Oxazoline-imidazolinylidene, – imidazolylidine, -benzimidazolylidene Hydrogenation Catalysts. J. Org. Chem. 2013, 78, 9969-9974....

Name : Dr. Winai Ieawsuwan (Research Scientist) Office Address : Room : R514B / R303C Laboratory of Medicinal Chemistry 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel : +66 2553 8555 (ext. 3052, 3024) Email : [email protected] Research Interests Synthetic methodology Asymmetric catalysis Total synthesis of natural products Education 2005 – 2009 Dr. Phil. Nat Organic Chemistry, Goethe University Frankfurt am Main, Germany 2001 – 2004 M.Sc. Organic Chemistry, Mahidol University, Thailand 1997 – 2001 B.Sc. Chemistry, Silpakorn University, Thailand Work Experiences 2020 – present Research Scientist I, Chulabhorn Research Institute, Thailand 2011 – 2020 Research Scientist, Chulabhorn Research Institute, Thailand 2009 – 2010 “Postdoctoral researcher, Université catholique de Louvain, Belgium.” 2008 “Laboratory assistant for organic chemistry course, Goethe University Frankfurt am Main, Germany.” 2004 – 2005 Research assistant, Mahidol University, Bangkok, Thailand. Awards 1997 – 2004 The Development and Promotion of Science and Technology Talent Project (DPST) Scholarship 2002 – 2004 The Postgraduate Education and Research Program in Chemistry (PERCH). 2005 – 2009 Degussa Endowed Professorship from Prof. Dr. Magnus Rueping. 2009 – 2010 Postdoctoral fellowship from Prof. Dr. Istvan E. Marko. 2013 “Good Award on the thesis award 2013” National Research Council of Thailand (NRCT), Thailand 2007 IUPAC Poster Prize at The German Chemical Society Biennial Congress: “GDCh Chemistry Forum” (Wissenschaftsforum Chemie), University...

Name : Dr. Wannaporn Disadee (Research Scientist I) Office Address : Room : R614B/R603 Laboratory of Medicinal Chemistry 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel : +66 2553 8555 (ext. 3081, 3090, 3091) Email : [email protected] Research Interests One-pot Tandem Reaction and Green Synthetic Methodology Organocatalytic Asymmetric Synthesis Total Synthesis of Biologically Active N-Heterocycles Education 2003 – 2006 Ph.D Pharmaceutical Sciences in Medicinal Organic Chemistry, Chiba University, Japan 2001 – 2003 M.Sc. Pharmaceutical Sciences in Medicinal Organic Chemistry, Chiba University, Japan 1995 – 1999 B.Sc. Chemistry, (1st class honor), Chulalongkorn University, Thailand Work Experiences 2015 – present Research Scientist I, Chulabhorn Research Institute, Thailand 2006 – 2015 Research Scientist, Chulabhorn Research Institute, Thailand Awards 2015 Science and Technology Research Grant, Thailand Toray Science Foundation, Thailand 2014 ACP Lectureship to Taiwan, Asian CORE Program-NRCT 2000 – 2006 Monbukagakusho Scholarship, Japan 1998 Award for Excellence Academic Performance in Undergraduate Study, Dr. Tab Nilanidhi Foundation, Thailand 1997 Department of Chemistry Award of Excellence, Chulalongkorn University, Thailand 1995 – 1999 Development and Promotion of Science and Technology Talents Project (DPST), Thai government scholarship, Thailand Publications Selected Publications Disadee, W.; Trisupphakant, K.; Ruchirawat, S. Synthesis of Novel Fluorescent Bicyclic Amidines and Evaluation of Their Photophysical Properties. Heterocycles 2022, 105, 417–437. Disadee, W.; Ruchirawat, S. Oxazaborolidine-catalyzed Reductive Parallel Kinetic Resolution...

Name : Dr. Rattana Worayuthakarn (Research Scientist) Office Address : Room : R413 / R403B Laboratory of Medicinal Chemistry 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel : +66 2553 8555 (ext. 3044) Email : [email protected] Research Interests Synthetic methodology Total synthesis of natural products Education 2001 – 2006 Ph.D Organic Chemistry, Mahidol University, Thailand 1998 – 2000 M.Sc. Organic Chemistry, Prince of Songkla University, Hat Yai, Thailand 1994 – 1997 B.Sc. Chemistry, Prince of Songkla University, Hat Yai, Thailand Work Experiences 2006 – 2019 Research Assistant, Chulabhorn Research Institute, Thailand 2019 – present Research Scientist, Chulabhorn Research Institute, Thailand Awards 2001-2003 Scholarship of The institutional strengthening program, Mahidol University 2001-2004 The Postgraduate Education and Research Program in Chemistry (PERCH), Mahidol University 2004-2006 Programme on Research and Development of Synthetic Drugs, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Nakornpathom, Thailand Publications Selected Publications Worayuthakarn, R.; Suddee, N.; Nealmongkol, P.; Ruchirawat, S.; Thasana, N. Copper-mediated C-O/C-N Bond Formation: A Facile Synthesis of 3-Amidocoumarin, 3-Amidoazacoumarin, and N-Aeroylindole Derivatives. Synlett 2022, 33, 1431–1437. Worayuthakarn, R.; Deesiri, S.; Chainok, K.; Wannarit, N.; Ruchirawat, S.; Thasana, N. Highly Regioselective Tandem Reaction of Ene-Yne-Oxazolones Induced by H-Phosphonates: Construction of Phosphinylindane Derivatives. J. Org. Chem. 2021, 86, 9360–9383. Pramthaisong, C.; Worayuthakarn R.; Pharikronburee, V.; Duangthongyou, T.;...

Name : Dr. Poonsakdi Ploypradith (Expert Scientist) Office Address : Room : R517 / R403B Laboratory of Medicinal Chemistry 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel : +66 2553 8555 (ext. 3069, 3044) Email : [email protected] Research Interests Synthetic methodology: stereoselective cyclization Total synthesis of natural products Medicinal chemistry of selected bioactive natural/synthetic compounds Education 1997 – 1999 Ph.D. Organic Chemistry, The Johns Hopkins University, U.S.A. 1994 – 1996 M.A. Organic Chemistry, The Johns Hopkins University, U.S.A. 1990 – 1994 B.A. Chemistry, The Johns Hopkins University, U.S.A. Work Experiences 2022 – present Expert Scientist, Chulabhorn Research Institute, Thailand 2015 – 2022 Research Scientist II, Chulabhorn Research Institute, Thailand 2009 – 2015 Research Scientist I, Chulabhorn Research Institute, Thailand 2000 – 2009 Research Scientist, Chulabhorn Research Institute, Thailand 2007 – present Lecturer, Program in Chemical Sciences, Chulabhorn Graduate Institute, Thailand Awards 2017 Lectureship Award to Taiwan (Asian Core Program) 2017 Lectureship Award to Korea (Asian Core Program) 2011 Lectureship Award to Hong Kong (Asian Core Program) 2011 Lectureship Award to Malaysia (Asian Core Program) 2009 Lectureship Award to Taiwan (Asian Core Program) 2009 Lectureship Award to Singapore (Asian Core Program) 2008 Lectureship Award to Korea (Asian Core Program) 2008 Lectureship Award to China (Asian Core Program) 1995 The Ernest M Marks Award for Excellence in...