Scott D. Rychnovsky

Picture of Scott D. Rychnovsky
Distinguished Professor, Chemistry
School of Physical Sciences
Ph.D., Columbia University, 1986
B.S. 1981, University of California at Berkeley
Phone: (949) 824-8292
University of California, Irvine
3038B FRH
Mail Code: 2025
Irvine, CA 92697
Research Interests
Organic Chemistry, Synthesis and Structure Determination, Chemical Biology
Academic Distinctions
Arthur C. Cope Scholar Award
Fresenius Award
Zeneca Chemistry Award
Searle Scholar Fellow
Camille and Henry Dreyfus Foundation Teacher-Scholar
Eli Lilly Fellow
Pfizer Research Award in Synthetic Organic Chemistry
Alfred P. Sloan Fellow
National Science Foundation Presidential Young Investigator Award
S. T. Li Prize for Achievements in Science and Technology
Associate Editor for The Journal of Organic Chemistry
Fellow of the American Association for the Advancement of Science
Fellow of the American Chemical Society
Royal Society of Chemistry Pedler Award
NIH Postdoctoral Fellow, Harvard University
Faculty member at the University of Minnesota from 1988-1995
Joined UCI faculty in 1995
Research Abstract
New methods are at the heart of synthetic organic chemistry. We are developing new methods to form carbon-carbon bonds and to introduce stereogenic centers. For example, we are investigating a new Intramolecular Diels-Alder reaction directed by a silacycle that forms three new rings with good stereocontrol. The reaction leads to a rapid increase structural complexity, and will be applied to target-directed synthesis.

Our new methodology is developed in the context of natural product total synthesis. Natural products present a myriad of interesting and diverse structural types that continue to challenge the synthetic chemist. Given the tremendous advances in methods development over the last few decades, almost any natural product could be made by talented synthetic chemists, but often only after many person-years of painstaking labor. Our methods are designed to make the synthesis of targeted natural products much more rapid and efficient. We select synthetic targets based on interesting structural features and unusual biological activity. These synthetic targets are a focus for our new methods and provide a challenge against which to measure their effectiveness.

We have developed a number of cross-linkers to elucidate protein-protein interfaces of protein complexes. These protein complexes form the machinery of the cell, and understanding their structures is critical to understanding their functions. The cross-linkers were designed to cleave selectively in the collision induced dissociation (CID) step in MS-MS experiments. This innovations allowed the cross-linked peptides to be sequenced, and the contact surfaces between proteins to be mapped. This project is part of a long-standing collaboration with Prof. Lan Huang's group in the Department of Physiology & Biophysics at UC Irvine.
Available Technologies
Structural Dynamics of the Human COP9 Signalosome Revealed by Cross-linking Mass Spectrometry and Integrative Modeling. Craig Gutierrez, Ilan E. Chemmama, Haibin Mao, Clinton Yu, Ignacia Echeverria, Sarah A. Block, Scott D. Rychnovsky, Ning Zheng, Andrej Sali, and Lan Huang, , PNAS, 2020, Latest Article.
Relative and Absolute Structure Assignments of Alkenes Using Crystalline Osmate Derivatives for X-Ray Analysis. Alexander S. Burns, Charles Dooley III, Paul R. Carlson, Joseph W. Ziller, and Scott D. Rychnovsky, Org. Lett. 2019, 21, 10125–10129.
Total Synthesis of (–)-Himeradine A. Alexander Burtea, Jacob DeForest, Xinting Li, and Scott D. Rychnovsky, Angew. Chem. Int. Ed. 2019,58, 16193–16197.
Total Synthesis and Structure Revision of (–)-Illisimonin A, a Neuroprotective Sesquiterpenoid from the Fruits of Illicium simonsii. Alexander S. Burns and Scott D. Rychnovsky, J. Am. Chem. Soc. 2019, 141, 13295–13300.
Biosynthesis-inspired Approach to Kujounin A2 Using a Stereoselective Tsuji-Trost Alkylation. Alexander Burtea and Scott D. Rychnovsky, Org. Lett. 2018, 20, 5849–5852.
Heteroatom-directed Acylation of Secondary Alcohols to Assign Absolute Configuration. Alexander S. Burns, Christopher C. Ross and Scott D. Rychnovsky, J. Org. Chem. 2018, 83, 2504–2515.
Second-Generation Synthesis of (+)-Fastigiatine Inspired by Conformational Studies. Jacob C. DeForest, Renzo A. Samame, Gregory Suryn, Alexander Burtea, and Scott D. Rychnovsky, J. Org. Chem. 2018, 83, 8914–8925
Developing a Novel Sulfoxide-containing MS-cleavable Homobifunctional Cysteine Reactive Cross-linker for Studying Protein-Protein Interactions. Craig B. Gutierrez, Sarah A. Block, Clinton Yu, Stephanie M. Soohoo, Alexander S. Huszagh, Scott Rychnovsky, Lan Huang, Anal. Chem. 2018, 90, 7600-7607.
Determination of the Absolute Configuration of ß-Chiral Primary Alcohols Using the Competing Enantioselective Conversion Method. Alexander S. Burns, Alexander J. Wagner, Jennifer L. Fulton, Kyle Young, Armen Zakarian, and Scott D. Rychnovsky, Org. Lett. 2017, 19, 2953–2956.
Concise Synthesis of (+)-Fastigiatine. Renzo A. Samame, Christina M. Owens and Scott D. Rychnovsky, Chem. Sci. 2016, 7, 188-190.
Developing a Novel Acidic Residue Reactive and Sulfoxide-containing MS-cleavable Homobifunctional Cross-linker for Probing Protein-Protein Interactions. Craig B. Gutierrez, Clinton Yu, Eric J. Novitsky, Alex S. Huszagh, Scott Rychnovsky, Lan Huang, Anal. Chem. 2016, 88, 8315–8322.
Synthesis of Two New Enrichable and MS-Cleavable Cross-linkers to Define Protein-Protein Interactions by Mass Spectrometry. Anthony M. Burke, Wynne Kandur, Eric J. Novitsky, Robyn M. Kaake, Clinton Yu, Athit Kao, Lan Huang and Scott D. Rychnovsky, Org. Biomol. Chem. 2015, 13, 5030-5037.
A Cross-linking Mass Spectrometry Platform to Define Protein Interactions in Living Cells. Robyn M. Kaake, Xiaorong Wang, Anthony Burke, Clinton Yu, Wynne Kandur, Yingying Yang, Eric J. Novitsky, Tonya Second, Jicheng Duan, Athit Kao, Shenheng Guan, Danielle Vellucci, Scott D. Rychnovsky, Lan Huang, Mol. Cell. Proteomics, 2014, 13, 3533-3543.
Mapping the structural topology of the yeast 19S proteasomal regulatory particle using chemical cross-linking and probabilistic modeling. Athit Kao, Arlo Randall, Yingying Yang, Vishal R. Patel, Wynne Kandur, Shenheng Guan, Scott D. Rychnovsky, Pierre Baldi, and Lan Huang, Mol. Cell. Proteomics 2012, 11, Epub. (DOI: 10.1074/mcp.M112.018374)
Professional Societies
American Chemical Society
Other Experience
Univeristy of Minnesota 1988—1995
Program Director
National Science Foundation 2015—2017
Graduate Programs
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