Research Interests

Our research interest lies in the area of development of new methodologies for organic transformations, target oriented synthesis of biologically important natural compounds, and diversity oriented synthesis of natural product-like molecules. Molecules thus built will be employed in the investigation of biologically significant processes. Each project described below encompasses more than one area of these research interests.

A Proposed Synthesis of Antinociceptive Resiniferatoxin

In its practice, developing new organic transformations is multifaceted. As part of our endeavor to synthesize resiniferatoxin, a "vinylogous pinacol rearrangement" is proposed for the construction of hydroazulene system from trans-decalin framework. This new reaction is of critical use for the synthesis of resiniferatoxin.

Syntheses of 2-Deoxy-2-Amino Sugars

A universal method to synthesize various natural and unnatural glycosamines from their anhydrous sugar precursors is another area of interest. With the unparalleled expansion of our understanding in glycobiology over the past decade, there is no better time for this effort.

Diversity Oriented Synthesis of Chiral Multicyclic Compounds based on Asymmetric Organic Catalysis

Asymmetric organic catalysis is drawing much attention in recent years. Simplicity and environmental friendliness in its practice are two of many advantages that organic catalysis renders. Catalytic amount of single organic molecule is used to furnish a series of enantiomerically pure organic molecules. The single asymmetric center in the dihydrofuran thus created will control the face from which dienophiles approach the diene. Thereby, a library of enantiomerically pure tricyclic compounds will arise.

Asymmetric Syntheses of MDR Antibiotic Guanacastepene A and the Combinatorial Synthesis of its Analogs

Emergence of vancomycin-resistant Enterococcus (VRE) in conjunction with methhicillin-resistant S. aureus (MRSA) has become a tremendous threat to human health since vancomycin has been the last resort for treating infections caused by MRSA. Isolation of guanacastepene A and its antibiotic activity against MRSA and VRE has attracted many interests in the synthetic community. We are also involved in the concise 14-step synthesis of guanacastepene A. Unfortunately, guanacastepene A demonstrates hemolytic activity as well as its activity against multi drug-resistant strains of pathogenic bacteria. Our plan is to apply the scheme developed in its total synthesis to the solid-phase split-pool synthesis of guanacastepene analogs. Combined with comparative assays against red blood cells and pathogenic bacteria, a library of guanacastepene A-like compounds presents a possibility of discovering a new multi drug-resistant antibiotic.

Publications

Y. S. Tran; O. Kwon, "An Application of the Phosphine-Catalyzed [4 + 2] Annulation in Indole Alkaloid Synthesis: Formal Syntheses of (±)-Alstonerine and (±)-Macroline" Org. Lett. 2005, published on the web on August 23.

X.-F. Zhu; A.-P. Schaffner; R. C. Li; O. Kwon, "Phosphine-Catalyzed Synthesis of 6-Substituted 2-pyrones: Manifestation of E/Z-Isomerism in the Zwitterionic Intermediate" Org. Lett. 2005, 7, 2977-2980.

X.-F. Zhu; C. E. Henry; O. Kwon, "A highly diastereoselective synthesis of 3-carbethoxy-2,5-disubstituted-3-pyrrolines by phosphine catalysis" Tetrahedron, 2005, 61, 6276-6282.

X.-F. Zhu; C. E. Henry; J. Wang; T. Dudding; O. Kwon, "Phosphine-Catalyzed Synthesis of 1,3- Dioxan-4-ylidenes" Org. Lett. 2005, 7, 1387-1390.

X. Du; H. V. Chu; O. Kwon, "A Concise Synthesis of the Functionalized [5-7-6] Tricyclic Skeleton of Guanacastepene A" Tetrahedron Lett., 2004, 45, 8843-8846.

D. R. Schmidt; O. Kwon; S. L. Schreiber, "Macrolactones in Diversity-Oriented Synthesis: Preparation of a Pilot Library and Exploration of Factors Controlling Macrocyclization" J. Comb. Chem. 2004, 6, 286-292

Co-inventor on a US Patent Application entitled: "Generation of SkeletalDiversity Within a Combinatorial Library", Serial Number 10/640,834, filed August 14, 2003.

X. Du; H. V. Chu; O. Kwon, "Synthesis of the [5-7-6] Tricyclic Core of Guanacastepene A via an Intramolecular Mukaiyama Aldol Reaction" Org. Lett., 2003, 5, 1923-1926.

X.-F. Zhu; J. Lan; O. Kwon, "An Expedient Phosphine-Catalyzed [4+2] Annulation: Synthesis of Highly Functionalized Tetrahydropyridines" J. Am. Chem. Soc., 2003, 125, 4716-4717

O. Kwon; S. B. Park; S. L. Schreiber, "Skeletal Diversity via a Branched Pathway: Efficient Synthesis of 29 400 Discrete, Polycyclic Compounds and Their Arraying into Stock Solutions" J. Am. Chem. Soc., 2002, 124, 13402-13404.

O. Kwon; D.-S. Su; D. Meng; W. Deng; D. C. D'Amico; S. J. Danishefsky, "A Stereospecific Geminal Alkylation Scheme En Route To CP-225,917 and CP-263,114" Angew. Chem. Int. Ed. Engl. 1998, 37, 1880-1882.

O. Kwon; D.-S. Su; D. Meng; W. Deng; D. C. D'Amico; S. J. Danishefsky, "Total Syntheses of CP-225,917 and CP-263,114: Creation of a Matrix Structure By Sequential Aldol Condensation and Intramolecular Heck Ring Closure" Angew. Chem. Int. Ed. Engl. 1998, 37, 1877-1880.

O. Kwon; S. J. Danishefsky, "Synthesis of Asialo GM1. New Insights in the Application of Sulfonamidoglycosidation in Oligosaccharide Assembly: Subtle Proximity Effects in the Stereochemical Governance of Glycosidation" J. Am. Chem. Soc. 1998, 120, 1588-1599.

T. K. Park; I. J. Kim; S. Hu; M. T. Bilodeau; J. T. Randolf; O. Kwon; S. J. Danishefsky, "Total Synthesis and Proof of Structure of a Human Breast Tumor (Globo-H) Antigen" J. Am. Chem. Soc. 1996, 118, 11488-11500.

E. Lee; Y. R. Lee; B. Moon; O. Kwon; M. S. Shim; J. S. Yun, "Oxyanion Orientation in Anionic Oxy-Cope Rearrangement" J. Org. Chem. 1994, 59, 1444-1456.