Total Synthesis of 1,4a-di-epi-ent-Pancratistatin, Exemplifying a Stereodivergent Approach to Pancratistatin Isomers

The total synthesis of 1,4a-di--pancratistatin, a novel stereoisomer of the anti-tumor alkaloid pancratistatin, was achieved in 14 steps starting from D-mannitol. The construction of the pancratistatin skeleton involved conjugate addition of organocuprate to a nitrosoolefin, which was generated from inosose oxime. This was followed by stereoselective reduction of the oxime to an amine and site-selective formylation. Biological evaluations revealed that the newly synthesized compounds exhibit cytotoxicity toward cancer cells and significant ferroptosis inhibitory activity. These compounds constitute a promising small-molecule library for the development of potent bioactive agents.


5-exo-Selective Asymmetric Bromolactonization of Stilbenecarboxylic Acids Catalyzed by Phenol-bearing Chiral Thiourea

We developed a novel thiourea Lewis-base catalyst with phenol moieties for the enantioselective 5--bromolactonization of stilbenecarboxylic acids to afford chiral 3-substituted phthalides. The phenol moieties are crucial for the enantio- and regio-selectivity.


Evaluation of Quantum Chemistry Calculation Methods for Conformational Analysis of Organic Molecules Using A-Value Estimation as a Benchmark Test.

A-values of 20 substituents were estimated by quantum chemistry calculations of different theoretical levels. Comparison with the reported experimental values provided a good benchmark to evaluate the theoretical levels for the conformational analysis of organic molecules.


Efficient Synthesis of Medium-sized Nitrogen Heterocycles by Brønsted Acid-Catalyzed Cyclization of Ene-ynamides


Remote Electronic Effect of Chiral N-Heterocyclic Carbene Catalyst on an Asymmetric Benzoin Reaction

A remote electronic effect of chiral aminoindanol-derived N-heterocyclic carbene catalyst on an asymmetric benzoin reaction was investigated. The catalyst bearing remote electron-withdrawing substituents increased enantioselectivity of the reaction at the cost of the reaction rate. DFT calculations rationalized the increased enantioselectivity.


Remote electronic effect on the N-heterocyclic carbene-catalyzed asymmetric intramolecular Stetter reaction and structural revision of products

The remote electronic effects of chiral N-heterocyclic carbene catalysts on the asymmetric intramolecular Stetter reaction are investigated. The reaction rate and enantioselectivity were markedly influenced by a substituent at a remote position of the catalyst. The absolute configurations of the products are revised by X-ray diffraction. Density-functional theory calculations rationalize the improvement of the enantioselectivity using an electron-deficient catalyst.


Catalytic and Aerobic Oxidative C-H Annulation Reaction of Saturated Cyclic Amines for Synthesis of Dipyrroloquinolines


Preparation of N-2-Nitrophenylsulfenyl Imino Peptides and Their Catalyst-Controlled Diastereoselective Indolylation

N-2-Nitrophenylsulfenyl (Nps) imino dipeptides bearing various functional groups were successfully prepared via MnO2mediated oxidation and then subjected to diastereoselective indolylation. Each diastereomer of the adduct was selectively obtained from the same substrates using the appropriate chiral phosphoric acid catalysts. These transformations would be useful for synthesizing non-canonical amino acid-containing peptides as novel drug candidates.


Kinetic Resolution of α-Hydroxyamide via N-Heterocyclic Carbene-Catalyzed Acylation


Lewis Acid-Catalyzed Diastereoselective Domino Reaction of Ene-Ynamide with Trimethylsilyl Cyanide to Construct Spiroindolines

The Zn(OTf)-catalyzed domino reaction of enamide-ynamides in the presence of trimethylsilyl cyanide as an external nucleophile to construct spirocyclic indolines was developed. This domino reaction involved cyclization of enamide to ynamide to generate 4',5'-dihydrospiro[indoline-3,3'-pyrrol]-1'-ium followed by cyanide addition to produce spiroindolopyrrolidines with good diastereoselectivity.


Enhanced Molecular Recognition through SubstrateAdditive Complex Formation in N-Heterocyclic-Carbene-Catalyzed Kinetic Resolution of alpha-Hydroxythioamides.


The Rationale for Stereoinduction in Conjugate Addition to Alkylidenemalonates Bearing a Menthol-derived Chiral Auxiliary


Mechanistic Support for Intramolecular Migrative Cyclization of Propargyl Sulfones Provided by Catalytic Asymmetric Induction with a Chiral Counter Cation Strategy


Helical Nanographenes Embedded with Contiguous Azulene Units

Journal of the American Chemical Society


Cloning and Expression of a Perilla frutescens Cytochrome P450 Enzyme Catalyzing the Hydroxylation of Phenylpropenes


Asymmetric Synthesis of α-Amino Phosphonic Acids Using Stable Imino Phosphonate as a Universal Precursor


Total Syntheses of Allelopathic 4-Oxyprotoilludanes, Melleolides, and Echinocidins

Stereocontrolled total syntheses of allelopathic 4-oxyprotoilludane sesquiterpenes, melleolide, melleolide F, and echinocidins B and D were achieved. The curved 5/6/4 tricyclic system with an angular hydroxy group was built via three key transformations: (1) MeAl-catalyzed [2 + 2] cycloaddition of a ketene silyl acetal with a propiolate, (2) reductive ring-opening of a cyclic hemiketal, and (3) the intramolecular Morita-Baylis-Hillman reaction. This synthetic route represents a new and reliable strategy to obtain protoilludanes with several oxy-functional groups.


Synthesis of Functionalized MediumSized transCycloalkenes by 4π Electrocyclic Ring OpeningAlkylation Cascade


Rapid Assembly of Protoilludane Skeleton through Tandem Catalysis: Total Synthesis of Paesslerin A and Its Structural Revision.

A multicomponent domino reaction involving three mechanistically distinct TfNH-catalyzed reactions was developed. The reaction cascade enables the assembly of a skewed 5/6/4 tricyclic motif with migration of the reactive site with the assistance of a catalyst. The tricyclic product was used to achieve the first total synthesis of cytotoxic paesslerin A by regioselective C-H insertion of the sulfonyl carbenoid and base-promoted olefin isomerization. Our results led to the revision of the originally proposed tricyclic structure of paesslerin A.


Asymmetric Formal Synthesis of (+)-Catharanthine via Desymmetrization of Isoquinuclidine

Although (+)-catharanthine is an attractive alkaloid for both clinical research and organic synthetic chemistry, only a limited number of approaches for its catalytic asymmetric synthesis exist. Herein, we describe a novel strategy for synthesizing a chiral intermediate of (+)-catharanthine via phosphoric acid-catalyzed asymmetric desymmetrization of a meso-isoquinuclidine possessing a 1,3-diol unit that was synthesized by a formal amide insertion reaction.


Optical Resolution via Catalytic Generation of Chiral Auxiliary


Aminolithiation-Arylation Consecutive Cyclization of N-(2-Fluorophenyl)methyl-aminoalkylstyryls Giving Aryl-substituted Pyrido[1,2-b]isoquinoline.


A recyclable hydrophobic anchor-tagged asymmetric amino thiourea catalyst


Direct enantioselective indolylation of peptidyl imine for the synthesis of indolyl glycine-containing peptides


TOTAL SYNTHESIS OF PHENANTHROQUINOLIZIDINE ALKALOID CRYPTOPLEURINE AND PHENANTHROINDOLIZIDINE ALKALOID TYLOPHORINE


Consecutive Aminolithiation Carbolithiation of a Linear Aminoalkene Bearing Terminal Vinyl Sulfide Moiety to Give Hydro indolizine


Synthesis of π-Extended Fluoranthenes via a KHMDS-promoted Anionic-Radical Reaction Cascade.

An unprecedented KHMDS-promoted domino reaction to furnish hydroxyfluoranthenes is described. Biaryl compounds bearing acyl and naphthylalkenyl moieties are transformed into 9-hydroxydibenzo[j,l]fluoranthenes in a single step through the formation of an aromatic and a pentagonal ring system. A variety of fluoranthenes including those with extended π-conjugation, a heteroaromatic ring, and unsymmetrical substituents could be synthesized. Mechanistic studies reveal a unique reaction cascade where KHMDS acts as both a base and a single-electron donor.


Synthesis of Multi-Substituted Cyclobutenes: Cyclic Strategy for [2+2] Cycloadditon of Ketene Silyl Acetals with Propiolates.


Synthesis and Biological Evaluation of Steroidal Derivatives Bearing a Small Ring as Vitamin D Receptor Agonists.

A novel series of 3-ketolithocholic acid derivatives as well as estrone derivatives bearing a small ring for the conformational fixation of the side chain were synthesized by using a catalytic [2+2] cycloaddition and a ring-contraction rearrangement. The steroidal derivatives were evaluated for transcriptional activation of vitamin D receptor by luciferase reporter assays. Among them, two estrone derivatives showed a higher efficacy of the transactivation of vitamin D receptor than 3-ketolithocholic acid, and the small ring moieties were found to be important for the efficacy.

Bioorganic & Medicinal Chemistry Letters


Site-selective Benzoin-type Cyclization of Unsymmetrical Dialdoses Catalyzed by N-Heterocyclic Carbenes for Divergent Cyclitol Synthesis.

A highly site-selective N-heterocyclic carbene (NHC)-catalyzed benzoin-type cyclization of unsymmetrical dialdoses is developed to enable a divergent cyclitol synthesis. The choice of chiral NHCs and protecting groups affects the site-selectivity. The resulting inososes are converted into epi-, muco- and myo-inositols, and their chiral protected derivatives are formed in good yields.


Phosphine-Promoted Migrative Cyclization of Sulfonylalkynol and Sulfonylalkynamide for the Synthesis of Oxa- and Azacycles.


Use of a Catalytic Chiral Leaving Group for Asymmetric Substitutions at sp3-Hybridized Carbon Atoms: Kinetic Resolution of beta-Amino Alcohols by p-Methoxybenzylation .


Desymmetrization of Acid Anhydride with Asymmetric Esterification Catalyzed by Chiral Phosphoric Acid.


Striking Difference between Succinimidomethyl and Phthalimidomethyl Radicals in Conjugate Addition to Alkylidenemalonate Initiated by Dimethylzinc.

We used dimethylzinc to develop a conjugate addition reaction of imidomethyl radicals to alkylidenemalonates, in which we observed a significant difference between succinimidomethyl and phthalimidomethyl radicals. This reaction provides new access to γ-aminobutyric acid derivatives, which often function as neurotransmitters.


Oxa- and Azacycle-formation via Migrative Cyclization of Sulfonylalkynol and Sulfonylalkynamide with N-Heterocyclic Carbene.

An N-heterocyclic carbene promotes cyclization of sulfonylalkynols and sulfonylalkynamides that accompanies 1,2-migration of the sulfonyl groups. This reaction provides a novel access to oxa- and azacycles possessing a pendent vinyl sulfone functionality, which, in turn, is amenable for further transformations.


Exploration of Dimethylzinc-Mediated Radical Reactions.

In this account, our studies on radical reactions that are promoted by dimethylzinc and air are described. Advantages of this reagent and differences from conventional radical initiators, such as triethylborane, are discussed.


An Arylative Ring Expansion Cascade of Fused Cyclobutenes via Short-Lived Intermediates with Planar Chirality.

An arylative ring expansion cascade has been developed for the synthesis of medium-sized carbocycles from fused cyclobutenes. This reaction proceeds through a short-lived cis,trans-cycloalkadiene intermediate that is formed by thermal 4ϖ electrocyclic ring opening. Chirality transfer experiments provide direct evidence for the transient generation of the intermediate.

Journal of the American Chemical Society


Asymmetric Total Synthesis of Tylophorine via a Formal [2+2] Cycloaddition Followed by Migrative Ring Opening of a Cyclobutane.


Organocatalytic Activation of the Leaving Group in the Intramolecular Asymmetric SN 2' Reaction.

A Brønsted-acid-catalyzed intramolecular enantioselective SN 2' reaction was developed utilizing trichloroacetimidate as a leaving group. The findings indicated that dual activation of the substrates is operative. This metal-free allylic alkylation allows highly enantioselective access to 2-vinylpyrrolidines bearing various substituents.


Cyclic Model for the Asymmetric Conjugate Addition of Organolithium with Enoate.


A Short Synthesis of (+)-β-Lycorane by Asymmetric Conjugate Addition Cascade.


Hydrostannylation-Cross-Coupling Strategy for Stereoselective Synthesis of Alkylidenemalonates and Related α,β-Unsaturated Esters.


N-Heterocyclic Carbene-Catalyzed Benzoin Strategy for Divergent Synthesis of Cyclitol Derivatives from Alditols.


Synthesis of Steroidal Derivatives Bearing a Small Ring Using a Catalytic [2+2] Cycloaddition and a Ring-Contraction Rearrangement.


Contiguous Radical Pivaloyloxymethylation-Directed C(sp3)-H Iodination of N-Tosyl Cycloalkanecarbaldimine.