Scott D. Rychnovsky

picture of Scott D. Rychnovsky

Professor, Chemistry
School of Physical Sciences

Ph.D., Columbia University, 1986


B.S. 1981, University of California at Berkeley

Phone: (949) 824-8292
Email: srychnov@uci.edu

University of California, Irvine
3038B FRH
Mail Code: 2025
Irvine, CA 92697
Research Interests
Organic Chemistry, Synthesis and Structure Determination, Chemical Biology
URL
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
Appointments
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 the Prins cyclization reaction, in which a new ring is formed along with a carbon-carbon bond and up to three new stereogenic centers. The potential of this reaction is further enhanced by our recent observation that carbon nucleophiles will participate and trap the penultimate carbenium ion. The use of carbon nucleophiles leads to a rapid increase structural complexity.

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. Huang's group at UC Irvine.
Available Technologies
Publications
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.
 
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.
 
Stereochemical Outcomes in Reductive Cyclizations to Form Spirocyclic Heterocycles. Matthew A. Perry, Richard R. Hill, Justin J. Leong and Scott D. Rychnovsky, Org. Lett. 2015, 17, 3268-3271.
 
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.
 
Developing New Isotope-coded MS-cleavable Cross-linkers for Elucidating Protein Structures. Clinton Yu, Wynne Kandur, Athit Kao, Scott Rychnovsky and Lan Huang, Anal. Chem. 2014, 86, 2099-2106.
 
Formation of Highly Substituted Tetrahydropyranones: Application to the Total Synthesis of Cyanolide A. Gidget C. Tay, Michael R. Gesinski, and Scott D. Rychnovsky, Org. Lett. 2013, 15, 4536-4539.
 
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)
 
Nanomole-scale Assignment of Configuration for Primary Amines Using a Kinetic Resolution Strategy. Shawn M. Miller, Renzo A. Samame and Scott D. Rychnovsky, J. Am. Chem. Soc. 2012, 134, 20318-20321.
 
Development of a Novel Cross-Linking Strategy for Fast and Accurate Identification of Cross-Linked Peptides of Protein Complexes. Athit Kao, Chi-li Chiu, Danielle Vellucci, Yingying Yang, Shenheng Guan, Arlo Randall, Pierre Baldi, Scott D. Rychnovsky, Lan Huang, Mol. Cell. Proteomics 2011, 10, 1-17.
 
Total Synthesis of the Cyanolide A Aglycon. Mike R. Gesinski and Scott D. Rychnovsky, J. Am. Chem. Soc. 2011, 133, 9727-9729.
 
Determination of Absolute Configuration Using Kinetic Resolution Catalysts. Alexander J. Wagner, Jonathan G. David, and Scott D. Rychnovsky, Org. Lett. 2011, 13, 4470-4473.
 
Fully Substituted Carbon Centers By Diastereoselective Spirocyclization: Stereoselective Synthesis of (+)-Lepadiformine A. C. Matthew Perry, Matthew D. Morin, Brian W. Slafer, Scott A. Wolckenhauer and Scott D. Rychnovsky, J. Am. Chem. Soc. 2010, 132, 9591-9593.
Professional Society
American Chemical Society
Other Experience
Professor
Univeristy of Minnesota 1988—1995

Graduate Programs
Chemistry

Last updated
10/24/2018