selection of -methyladenosine-sensitive RNA-cleaving deoxyribozymes with 10-fold selectivity over unmethylated RNA.

RNA-cleaving DNAzymes (RCDs) are catalytically active DNA molecules that cleave a wide range of RNA targets with extremely high sequence-selectivity, but none is able to faithfully discriminate methylated from unmethylated RNA (typically <30-fold). We report the first efforts to isolate RCDs from a random-sequence DNA pool by selection that cleave RNA/DNA chimera containing -methyladenosine (mA), one of the most prevalent RNA modifications that plays important regulatory roles in gene expression and human cancers. A -acting deoxyribozyme, RCD1-S2, exhibits an observed rate constant ( ) of 5.

Switchable chemoselective aryne reactions between nucleophiles and pericyclic reaction partners using either 3-methoxybenzyne or 3-silylbenzyne.

Arynes are known to serve as highly reactive benzene-based synthons, which have gained numerous successes in preparing functionalized arenes. Due to the superb electrophilic nature of these fleeting species, however, it is challenging to modulate the designated aryne transformation chemoselectively, when substrates possess multiple competing reaction sites. Here, we showcase our effort to manipulate chemoselective control between two major types of aryne transformations using either 3-methoxybenzyne or 3-silylbenzyne, where nucleophilic addition-triggered reactions and non-polar pericyclic reactions could be differentiated.

Two Cascade Processes Initiated by the Insertion of Benzyne into the Se═O Bond.

Two sets of cascade processes have been realized, both of which were initiated with a benzyne insertion into the Se═O bond. The key factors to differentiate these processes are based on the structures of diaryl selenium oxides and reaction conditions. When diaryl selenium oxides containing an weak σ-electron-withdrawing group were used, triarylselenonium salts were obtained at room temperature, while -(aryloxy)phenyl phenyl selanes could be produced from diaryl selenium oxides at 100 °C.

Benzyne Polyfunctionalization via a Tandem C-C σ-Bond Insertion and Photo-Nazarov Cyclization.

A tandem benzyne C-C σ-bond insertion reaction and photo-Nazarov cyclization protocol was developed, leading to the formation of three C-C bonds at consecutive positions of a benzene ring with concomitant assembly of a 6-5-6 tricyclic ring system. When 3-silylbenzyne precursors were employed, a tandem process involving a benzyne C-C σ-bond insertion, a photo-Nazarov cyclization, and a 1,3-silyl group migration was observed, which could produce 1,2,3,5-tetrasubstituted benzenes.

Aryne 1,4-Disubstitution and Remote Diastereoselective 1,2,4-Trisubstitution via a Nucleophilic Annulation-[5,5]-Sigmatropic Rearrangement Process.

Both aryne 1,4-disubstitution and 1,2,4-trifunctionalization were accomplished from tertiary amines bearing a penta-2,4-dien-1-yl moiety. These transformations could directly incorporate a C-N and a C-C bond para to each other on an aryne intermediate via a sequential nucleophilic addition and [5,5]-sigmatropic rearrangement. When arynes bearing 3-tethered electrophiles were employed, a cascade regioselective nucleophilic addition, intramolecular cyclization, and remote diastereoselective [5,5]-sigmatropic rearrangement process was observed.

Diverse Synthesis of Triarylselenonium Salts and -(Alkoxy)aryl Aryl Selanes via Insertion of Benzyne into the Se═O Bond.

An insertion of benzyne into the Se═O bond has been realized. In this reaction, two types of compounds containing selenium could be synthesized from different substrates. When diaryl selenium oxides were used, triarylselenonium salts were furnished, while -(alkoxy)phenyl phenyl selanes could be produced from aryl alkyl selenium oxides.

The Stannum-Ene Reactions of Benzyne and Cyclohexyne with Superb Chemoselectivity for Cyclohexyne.

The stannum-ene reactions of both benzyne and cyclohexyne were realized, which is particularly suitable for cyclohexyne with a broad substrate scope and excellent chemoselectivity. Our DFT calculations via distortion/interaction analysis revealed that both stannum- and hydrogen-ene reactions with cyclohexyne have later transition states due to their higher distortion energies in the transition states than those in benzyne reactions, which lead to enhanced Pauli repulsion as the decisive factor in the interaction energy accompanied with enlarged energy gap between two types of ene reactions. Therefore, excellent chemoselectivity was disclosed in the cyclohexyne-ene reaction.

Benzyne-Mediated Esterification Reaction.

A benzyne-mediated esterification of carboxylic acids and alcohols under mild conditions has been realized, which is made possible via a selective nucleophilic addition of carboxylic acid to benzyne in the presence of alcohol. After a subsequent transesterification with alcohol, the corresponding esters can be produced efficiently. This benzyne-mediated protocol can be used on the modification of Ibuprofen, cholesterol, estradiol, and synthesis of nandrolone phenylpropionate.

Benzyne 1,2,4-Trisubstitution and Dearomative 1,2,4-Trifunctionalization.

Both 1,2,4-trisubstitution and dearomative 1,2,4-trifunctionalization of benzyne have been accomplished from sulfoxides bearing a penta-2,4-dien-1-yl moiety. These cascade transformations proceed through a benzyne insertion into the S═O bond and an uncommon regiospecific anionic [4,5]-sigmatropic rearrangement, furnishing a C-O, C-S, and C-C bond on the C1-, C2-, and C4-position of a benzene ring, respectively. This study showcases new cascade benzyne reaction modes involving both distal C-H bond functionalization and dearomatization.

-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors.

Arynes are among the most active organic intermediates and have found numerous applications in expeditious preparation of substituted arenes. In the past 20 years, chemists have witnessed a resurgence in aryne chemistry, which is mainly attributed by the extensive utilization of Kobayashi's method, a fluoride-induced removal of the TMS group with concomitant departure of its OTf group on -silylaryl triflates. Nowadays, -silylaryl triflates are the most frequently employed aryne precursors.

Aryne 1,2,3,5-Tetrasubstitution Enabled by 3-Silylaryne and Allyl Sulfoxide via an Aromatic 1,3-Silyl Migration.

Although benzyne has been well-known to serve as a synthon that can conveniently prepare various 1,2-difunctionalized benzenes, the sites other than its formal triple bond remain silent in typical benzyne transformations. An unprecedented aryne 1,2,3,5-tetrasubstitution was realized from 3-silylbenzyne and aryl allyl sulfoxide, the mechanistic pathway of which includes a regioselective aryne insertion into the S═O bond, a [3,6]-sigmatropic rearrangement, and a thermal aromatic 1,3-silyl migration cascade.

Arene Trifunctionalization with Highly Fused Ring Systems through a Domino Aryne Nucleophilic and Diels-Alder Cascade.

A convenient and efficient domino aryne process was developed under transition-metal-free conditions to generate a range of tetra- and pentacyclic ring systems. This transformation was realized via a 1,2-benzdiyne through a nucleophilic and Diels-Alder reaction cascade using styrene as the diene moiety. Three new chemical bonds, namely one C-N and two C-C bonds, and two benzofused rings could be constructed concomitantly, which was made possible by distinct chemoselective control at both the 1,2-aryne and 2,3-aryne stages.

Cyclohexenynone Precursors: Preparation via Oxidative Dearomatization Strategy and Reactivity.

A unique approach toward the preparation of cyclohexenynone equivalents was successfully developed via oxidative dearomatization of aryne precursors, featuring multiple functionalities on the target rings. Upon activation, these in situ formed cyclohexenynone intermediates exhibit good to excellent reactivity with various trapping agents. Moreover, an unprecedented cascade was discovered with aryl allyl sulfoxides, revealing a deeper utilization of the alkyne bond by concomitantly introducing one nucleophile and two electrophiles.

Domino Aryne Annulation via a Nucleophilic-Ene Process.

1,2-Benzdiyne equivalents possess the unique property that they can react with two arynophiles through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic-ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope.

Aryne multifunctionalization with benzdiyne and benztriyne equivalents.

One of the most distinct characters of aryne chemistry over other synthetic methodologies is its ability to simultaneously functionalize the vicinal two positions of a benzene ring with diverse combinations of substituents. Moreover, the functionalization of the remaining four positions can be also achieved through multiaryne equivalents, in which more than one triple bond is generated on the different locations of the same benzene ring. This tutorial review summarizes the applications of benzdiyne and benztriyne equivalents from the standpoint of synthetic organic chemistry as well as in the preparation of polycyclic aromatic functional frameworks.

Selective Aryne Formation via Grob Fragmentation from the [2+2] Cycloadducts of 3-Triflyloxyarynes.

A chemoselective ring-opening protocol of the formal [2+2] cycloadducts of 3-triflyloxyarynes was developed to generate 2,3-aryne intermediate via Grob fragmentation. A variety of 1,3-di- and 1,2,3-trisubstituted arenes could be readily accessed through this [2+2] cycloaddition-2,3-aryne formation sequence. The regioselectivity in these transformations originates from the steric repulsion of the aliphatic chain.

Aryne 1,2,3-Trifunctionalization with Aryl Allyl Sulfoxides.

An aryne 1,2,3-trisubstitution with aryl allyl sulfoxides is accomplished, featuring an incorporation of C-S, C-O, and C-C bonds on the consecutive positions of a benzene ring. The reaction condition is mild with broad substrate scope. Preliminary mechanistic study suggests a cascade formal [2 + 2] reaction of aryne with S═O bond, an allyl S → O migration, and a Claisen rearrangement.

Vicinal Diamination of Arenes with Domino Aryne Precursors.

Vicinal diamination of domino aryne precursors was achieved with sulfamides. The reaction proceeds through a two-aryne pathway, accepting two N-nucleophiles at the 1,2-positions of an arene ring. Symmetrical and unsymmetrical diaminobenzenes were readily obtained.

Diamination of Domino Aryne Precursor with Sulfonamides.

The reaction of a domino aryne precursor with sulfonamides efficiently afforded both 1,3-diaminobenzenes and trisubstituted 1,3-diaminobenzenes by simply varying the reaction conditions. Mechanistic study supports the sequential formation of two transient aryne intermediates involved in the reaction.

Robust Generalized Low Rank Approximations of Matrices.

In recent years, the intrinsic low rank structure of some datasets has been extensively exploited to reduce dimensionality, remove noise and complete the missing entries. As a well-known technique for dimensionality reduction and data compression, Generalized Low Rank Approximations of Matrices (GLRAM) claims its superiority on computation time and compression ratio over the SVD. However, GLRAM is very sensitive to sparse large noise or outliers and its robust version does not have been explored or solved yet.

Domino aryne precursor: efficient construction of 2,4-disubstituted benzothiazoles.

An aryne precursor with a potential to perform domino aryne chemistry was proposed and synthesized. The reaction of this reagent with benzothioamide derivatives could afford 2,4-disubstituted benzothiazole with sequential incorporation of C-S, C-N, and C-C bonds on the consecutive three positions of the aryne precursor.

Behaviour of topological marker proteins targeted to the Tat protein transport pathway.

The Escherichia coli Tat system mediates Sec-independent export of protein precursors bearing twin arginine signal peptides. Formate dehydrogenase-N is a three-subunit membrane-bound enzyme, in which localization of the FdnG subunit to the membrane is Tat dependent. FdnG was found in the periplasmic fraction of a mutant lacking the membrane anchor subunit FdnI, confirming that FdnG is located at the periplasmic face of the cytoplasmic membrane.