Yong-Suk Kwon

Catalysts that control stereochemistry are prized tools in chemical synthesis. When an effective catalyst is found, it is often explored for other types of reactions, frequently under the auspices of different mechanisms. As successes mount, a unique catalyst scaffold may become viewed as "privileged". However, the mechanistic hallmarks of privileged catalysts are not easily enumerated or readily generalized to genuinely different classes of reactions or substrates. We explored the concept of sc

Catalyst control over reactions that produce multiple stereoisomers is a challenge in synthesis. Control over reactions that involve stereogenic elements remote from one another is particularly uncommon. Additionally, catalytic reactions that address both stereogenic carbon centers and an element of axial chirality are also rare. Reported herein is a catalytic approach to each stereoisomer of a scaffold containing a stereogenic center remote from an axis of chirality. Newly developed peptidyl co

We report the catalytic stereocontrolled synthesis of dinucleotides. We have demonstrated, for the first time to our knowledge, that chiral phosphoric acid (CPA) catalysts control the formation of stereogenic phosphorous centers during phosphoramidite transfer. Unprecedented levels of diastereodivergence have also been demonstrated, enabling access to either phosphite diastereomer. Two different CPA scaffolds have proven to be essential for achieving stereodivergence: peptide-embedded phosphothr

An unprecedented example of a chiral phosphoric acid-catalyzed atroposelective Pictet-Spengler reaction of N-arylindoles is reported. Highly enantioenriched N-aryl-tetrahydro-β-carbolines with C-N bond axial chirality are obtained via dynamic kinetic resolution. The hydrogen bond donor introduced on the bottom aromatic ring, forming a secondary interaction with the phosphoryl oxygen, is essential to achieving high enantioselectivity. A wide variety of substituents are tolerable with this transfo

Due to their profound antiproliferative activity and unique mode of action, phenanthroindolizidine and phenanthroquinolizidine alkaloids, represented by antofine and cryptopleurine, have attracted attention recently as potential therapeutic agents. We have designed, synthesized, and evaluated the methanesulfonamide analogues of these natural alkaloids with the hope of improving their druglikeness. The analogues showed enhanced growth inhibition of human cancer cells compared with the parent natu

This paper documents the first example of In(III)-catalyzed selective 6-exo-dig hydroarylation of o-propargylbiaryls and their subsequent double-bond migration to obtain functionalized phenanthrenes. Electron-rich biaryl substrates undergo hydroarylation more effectively, and the substrates with various types of substituents on the alkyne can also be smoothly and selectively converted to phenanthrenes.

Cut, paste, and measure: The positions of double bonds in unsaturated long-chain compounds can be easily determined by chemical derivatization using a cross-metathesis reaction and chromatography–mass spectrometry. The produced olefins have distinct physicochemical properties suitable for LC/MS or GC/MS analysis that depend on the cross-metathesis partner used. This method is operationally simple and applicable at a sub-milligram scale. Detailed facts of importance to specialist readers are publ

Abstract Catalyst control over reactions that produce multiple stereoisomers is a challenge in synthesis. Control over reactions that involve stereogenic elements remote from one another is particularly uncommon. Additionally, catalytic reactions that address both stereogenic carbon centers and an element of axial chirality are also rare. Reported herein is a catalytic approach to each stereoisomer of a scaffold containing a stereogenic center remote from an axis of chirality. Newly developed pe

An efficient synthesis for phenanthrenes via a Pt-carbene intermediate is described. Using Pt as a catalyst, the readily accessible biphenyl propargyl alcohol substrate can be transformed to the vinylphenanthrene system through a cascade involving electrophilic cyclization, dehydration, and 1,2-H migration. The synthetic utility and efficiency of this protocol were demonstrated via the concise total synthesis of antofine.

Abstract An unprecedented example of a chiral phosphoric acid‐catalyzed atroposelective Pictet–Spengler reaction of N ‐arylindoles is reported. Highly enantioenriched N ‐aryl‐tetrahydro‐β‐carbolines with C−N bond axial chirality are obtained via dynamic kinetic resolution. The hydrogen bond donor introduced on the bottom aromatic ring, forming a secondary interaction with the phosphoryl oxygen, is essential to achieving high enantioselectivity. A wide variety of substituents are tolerable with t

Abstract Atropisomeric compounds have been discovered in pharmaceuticals and materials science, and their enantioselective syntheses have gained tremendous attention. Among strategies for catalytic atroposelective synthesis, desymmetrization provides robust and straightforward approaches to axially chiral biaryls. Due to the relative ease of substrate design compared to other atroposelective strategies, desymmetrization has emerged as a pivotal stage for converting fascinating chemistry into its

A series of carbocyclic analogues of naturally-occurring marine sphingolipid pachastrissamine were prepared and biologically evaluated. The analogues were efficiently synthesized via a tandem enyne/diene-ene metathesis reaction as a key step. We found that the analogue 4b exhibited comparable cytotoxicity and more potent inhibitory activity against sphingosine kinases, compared to pachastrissamine. Molecular modeling studies were conducted to provide more detailed insight into the binding mode o

As the complexity of organic molecules utilized by mankind increases, the phenomenon of atropisomerism is more frequently encountered. While a variety of well-established methods enable the control of a stereogenic center, a catalytic method for controlling a stereogenic axis in one substrate is typically unavailable for controlling axial chirality in other substrates with a similar structure. Herein, we report o-amidobiaryl as a flexible platform for chiral phosphoric acid-catalyzed atroposelec

Chemically modified proteins have diverse applications; however, conventional chemo-selective methods often yield heterogeneously labeled products. To address this limitation, site-specific protein labeling holds significant potential, driving extensive research in this area. Nevertheless, site-specific modification of native proteins remains challenging owing to the complexity of their functional groups. Therefore, a method for site-selective labeling of intact proteins is aimed to design. In t