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The efficient synthesis of 1-amino-1 H -indenes and 2,4-dienamides was realized via TfOH-catalyzed reactions of aryl methyl ketones with terminal ynamides in two distinct pathways. Aromatic ketones with high electrophilicity underwent [3 + 2] annulation with ynamides to produce 1-amino-1 H -indenes, while aromatic ketones with low electrophilicity proceeded under the same conditions to afford 2,4-dienamides. Furthermore, the obtained 1-amino-1 H -indenes could be converted into the corresponding 1 H -indenes and dihydro-1 H -indenes in excellent yields.

A metal-free TMSOTf-catalyzed [4 + 2] annulation of ynamides with β-(2-aminophenyl)-α,β-ynones enables the regiospecific and facile assembly of 2-aminoquinoline frameworks. The catalyst TMSOTf presented a remarkable advancement compared to previously reported transition-metal catalysts. A wide range of 3-aryl/alkyl-substituted 2-aminoquinolines were generated in moderate to excellent yields due to the mild conditions.

Two distinct TMSOTf-catalyzed annulation reactions between ynamides and 1,2-benzisothiazoles have been developed. The direction of the reaction could be easily switched by applying different thermodynamic-controlled conditions. At room temperature, ynamides undergo a [5 + 2] annulation reaction with 1,2-benzisothiazoles to afford 1,4-benzothiazepines, whereas under heating conditions a desulfurizative annulation reaction proceeds well to access 3-aminoisoquinolines. These two protocols provide biologically important 1,4-benzothiazepines and 3-aminoisoquinolines with high efficiency with broad substrate scopes under mild reaction conditions.

Here, we disclose an efficient TMSOTf-catalyzed C-H annulation of aryl-terminated N -arylynamides with sulfilimines, leading to the practical assembly of various valuable 2-aminoindoles in generally moderate to excellent yields with a broad range of functional groups, while nonaryl terminated N -arylynamides undergo TMSOTf-catalyzed aminative arylation with sulfilimines providing α-arylated amidines.

A copper-catalyzed cascade multicomponent reaction for synthesizing ditriazolyl diselenides from azides, terminal alkynes, and elemental selenium has been developed. The present reaction features utilizing readily available and stable reagents, high atom-economy, and mild reaction conditions. A possible mechanism is proposed.

Mass spectrometry (MS)-based metabolic profiling of the endophytic fungus Chaetomium nigricolor F5 guided the isolation of five novel cytochalasans, chamisides B-F ( 1-5 ), and two known ones, chaetoconvosins C and D ( 6 and 7 ). Their structures including stereochemistry were unambiguously determined by MS, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Compounds 1-3 share a new 5/6/5/5/7-fused pentacyclic skeleton in cytochalasans and are appropriately proposed to be the key biosynthetic precursors of co-isolated cytochalasans with a 6/6/5/7/5, 6/6/5/5/7, or 6/6/5 ring system. Remarkably, compound 5 with a relatively flexible side chain showed promising inhibition activity against the cholesterol transporter protein Niemann-Pick C1-like 1 (NPC1L1), expanding the function of cytochalasans.

An oxidative dehydrogenative coupling of thiols with alkanes via direct C(sp 3 )-H bond functionalization to form a new C-S bond and S═O double bond was developed. The present reaction features the use of readily available reagents and high step- and atom-efficiency, thus providing an efficient access to sulfoxides. A possible mechanism is proposed.

A novel metal-free annulation of ynamides with 2 H -azirines catalyzed by BF 3 ·Et 2 O is described, leading to the construction of polysubstituted 2-aminopyrroles in a facile, flexible, and atom-economical way. This synthetic strategy proceeds with efficiency, broad substrate scope, and short reaction time under mild reaction conditions. Furthermore, the obtained annulation products could be modified to generate diverse 2-iminopyrrole frameworks in high yields.

An efficient Tf 2 NH-catalyzed [2 + 2] cycloaddition of ynamides under mild conditions has been developed. Within short reaction times, various ynamides are transformed into the corresponding 3-aminocyclobutenones in good to excellent yields. This is the first example for the metal-free intermolecular [2 + 2] self-cycloaddition of ynamides. Meanwhile, the desired cycloaddition products can be easily transformed into aminonaphthol derivatives.

Surface-assisted laser desorption/ionization mass spectrometry (SALDI MS) has been successfully applied in the analysis of various small molecules. In this work, gold nanoparticles/thiol-β-cyclodextrin-functionalized TiO 2 nanowires (AuNPs/SH-β-CD-TiO 2 NWs) were prepared to enhance the performance of SALDI MS and mass spectrometry imaging (MSI). A monolithic TiO 2 film was first grown on an indium tin oxide (ITO) glass slide via a modified sol-gel method and treated in an alkaline environment to form nanowires. TiO 2 NWs were chemically modified by SH-β-CD for immobilizing AuNPs densely and strongly. Compared with the conventional organic matrix 2,5-dihydroxybenzoic acid (DHB), the prepared AuNPs/SH-β-CD-TiO 2 NWs showed superior performances on detection sensitivity, repeatability, and analyte coverage. Analytes typically detectable with negative-ion matrix-assisted laser desorption/ionization (MALDI) MS could also be observed using AuNPs/SH-β-CD-TiO 2 NWs in the positive ion mode. Its successful usage efficiently enhanced the SALDI MS detection of various small molecules such as carbohydrates, fatty acids, and bile acids in the positive ion mode. The developed SALDI substrate was further used to characterize and discriminate the natural and in vitro cultured Calculus Bovis, as well as natural and artificial Moschus. Furthermore, the spatial distribution of several natural products in spearmint leaves and potato tubers was explored by tissue imprinting and deposition on the AuNPs/SH-β-CD-TiO 2 NW surface for SALDI MSI in dual-polarity mode, respectively. The wide application and satisfied detection sensitivity make AuNPs/SH-β-CD-TiO 2 NWs ideal for SALDI MS and MSI of various natural products.

Acetyl-coenzyme A (acetyl-CoA) is an important donor for acetylation modifications of nutritional supplements. The existing enzymatic methods for acetyl-CoA synthesis suffer from cofactor dependence, donor inaccessibility, and biocatalyst instability, leading to its high cost. Hence, a promising alternative is highly desired. Herein, a maltose O -acetyltransferase (MAT) with cofactor independence had been identified as a stable acetyl-CoA-synthesizing biocatalyst in a screen of the Escherichia coli genome. Under the action of MAT, an anthraquinone medicine containing two acetyl groups, diacerein, was screened as an acetyl donor. Saturation mutagenesis at Glu125 was performed to increase the acetyl-CoA-synthesizing capacity of MAT, while decreasing the accompanying hydrolase activities. A mutant MAT-E125F was thus generated and could convert diacerein and CoA into the highest yield of 3892.70 mg/L acetyl-CoA. Moreover, MAT could synthesize puerarin 6″- O -acetate and other glycosyl esters through acetyl-CoA-dependent acetylation or diacerein-based transesterification reaction. To most of the tested glycosides, the transesterification efficiency was higher than that of acetylation. The mutant MAT-E125V acquired the highest conversion of 94.0% to puerarin 6″- O -acetate through transesterification, while MAT-E125N yielded the highest conversion of 68.5% through acetylation. Taking together, the multifunctional MAT displayed a potent acetyl-CoA- and glycosyl ester-synthesizing capacity using diacerein as an acetyl donor.

Engineered bacteria are promising bioagents to synthesize antitumor drugs at tumor sites with the advantages of avoiding drug leakage and degradation during delivery. Here, we report an optically controlled material-assisted microbial system by biosynthesizing gold nanoparticles (AuNPs) on the surface of Shewanella algae K3259 ( S. algae ) to obtain Bac@Au. Leveraging the dual directional electron transport mechanism of S. algae , the hybrid biosystem enhances in situ synthesis of antineoplastic tetrodotoxin (TTX) for a promising antitumor effect. Because of tumor hypoxia-targeting feature of facultative anaerobic S. algae , Bac@Au selectively target and colonize at tumor. Upon light irradiation, photoelectrons produced by AuNPs deposited on bacterial surface are transferred into bacterial cytoplasm and participate in accelerated cell metabolism to increase the production of TTX for antitumor therapy. The optically controlled material-assisted microbial system enhances the efficiency of bacterial drug synthesis in situ and provides an antitumor strategy that could broaden conventional therapy boundaries.

A novel metal-free [3+2] annulation of ynamides with anthranils provides a facile, flexible, environmentally friendly, and atom-economical route to 2-aminoindoles. This synthetic process proceeds with efficiency, excellent regioselectivity, and wide functional group tolerance under mild conditions. Moreover, the obtained 2-aminoindole products represent a multifunctional platform for the construction of various 2-aminoindolyl frameworks.

Phosphine ligands with up to six chiral sites were prepared, starting from 2-phenylphenol, via O - and P -alkylation, cyclization, and coupling. The chirality was transferred from ( L )-menthyl to phosphorus, α-carbon, and axis, to achieve excellent diastereoselectivities. During an intramolecular S N Ar reaction with alkoxyl as the leaving groups, the C-O bond was converted to a C-C bond. Both phosphine boranes and oxides could be used for the conversions, affording a series of cyclic phosphines.

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry (MS) has become an attractive complementary approach to matrix-assisted laser desorption/ionization (MALDI) MS. SALDI MS has great potential for the detection of small molecules because of the absence of applied matrix. In this work, a functionalized porous TiO 2 film immobilized with gold nanoparticles (AuNPs-FPTDF) was prepared to enhance SALDI MS performance. The porous TiO 2 films were prepared by the facile sol-gel method and chemically functionalized for dense loading of AuNPs. The prepared AuNPs-FPTDF showed superior performance in the detection and imaging of small molecules in dual-polarity modes, with high detection sensitivity in the low pmol range, good repeatability, and low background noise compared to common organic MALDI matrixes. Its usage efficiently enhanced SALDI MS detection of various small molecules, such as amino acids and neurotransmitters, fatty acids, saccharides, alkaloids, and flavonoids, as compared with α-cyano-4-hydroxycinnamic acid, 9-aminoacridine, and the three precursor substrates of AuNPs-FPTDF. In addition, the blood glucose level in rats was successfully determined from a linearity concentration range of 0.5-9 mM, as well as other biomarkers in rat serum with SALDI MS. More importantly, the spatial distribution of metabolites from the intact flowers of the medicinal plant Catharanthus roseus was explored by using the AuNPs-FPTDF as an imprint SALDI MS substrate in dual-polarity modes. These results demonstrate wide applications and superior performances of the AuNPs-FPTDF as a multifunctional SALDI surface with enhanced detection sensitivity and imaging capabilities.

Metal-organic frameworks (MOFs) have been explored as crystal sponges (CSs) to organic substrates, but attention had rarely been paid to inorganic substrates. Herein, hierarchical zirconium-based MOFs exhibiting different topological structures had been fabricated by modulating the functional groups of the V-shaped linkers, including a new 4-fold-interpenetrating one, which displays a great performance as a CS applicable to inorganic matter (I 2 and ReO 4 - ) even in the extreme conditions.

Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.

Postsynthetic metalation (PSM) has been employed as a robust method for the postsynthetic modification of metal-organic frameworks (MOFs). However, the lack of relevant information that can be obtained for the postsynthetically introduced metallic ions has hindered the development of PSM applications. Thanks to the advancement in single-crystal X-ray diffraction (SCXRD) technology, there have been a few recent examples in which successful postsynthetic introduction of single metal ions into MOFs occurred at the defined chelating sites. These works have provided useful explanations about the complicated host-guest chemistry involved in PSMs. On the other hand, there are only limited examples with crystallographic snapshots of the postsynthetic installation of metal clusters into the pores of MOFs using an ordinary SCXRD due to the loss of crystallinity of parent matrix during the PSM process. Herein, by the careful selection of starting materials and controlling the reaction conditions, we report the first crystallographic visualization of metal clusters inserted into Zr-based MOFs via PSM. The structural advantages of the parent Zr-MOF, which are inherited from the stable Zr 6 cluster and triazole-containing dicarboxylate ligand, ensure both the preservation of high crystallinity and the presence of flexible coordination sites for PSM. Furthermore, PSM of metal clusters in a MOF pore space enhances stability of the final samples while also imparting the functionality of a successful catalyst toward ethylene dimerization reaction. The related construction ideas and structural information detailed in this work can help lay the foundation for further advancements using the postmodification of MOFs as well as open new doors for the utilization of SCXRD technology in the field of MOFs.

A metal-free [2 + 2 + 2] cycloaddition of alkyne-cyanamides or ynamide-nitriles with ynamides is described for the efficient synthesis of amino-substituted α- and δ-carbolines. This novel methodology is environmentally friendly and allows for highly regioselective access to carboline derivatives in good to excellent yields with wide functional group tolerance.

The first cascade diastereoselective synthesis of oxazoloisoindolinones via the palladium-catalyzed decarboxylative ortho-acylation of N-benzoyl α-amino acid derivatives followed by double intramolecular cyclizations has been demonstrated. This reaction, using α-amino acids as directing groups and α-oxocarboxylic acids as the acylation source, features a broad substrate scope, good functional group tolerance, high regioselectivity, and excellent diastereoselectivity.

Herein, we report the construction of a neutral, radical-rich, cobalt valence tautomeric triangle, which consists of two types of radical groups including tetrazine-based bridges and semiquinone anions at high temperature and has traits of high intensity and density of sensing sites. The mechanism of the Valence Tautomerism process within the triangle has been illustrated as one electron transfer, preceding a two electrons transfer along with the phenomenon of spin flipping.

A highly effective metal-free formal inverse-electron-demand Diels-Alder reaction of 1,2-diazines with ynamides has been developed. This catalytic protocol is more environmentally friendly and allows for the construction of 2-aminonaphthalenes and 2-aminoanthracenes from 1,2-diazines and ynamides in good to high yields with wide diversity and functional group tolerance.

DNA nanodevices that mimic natural biomolecular machines changing configurations in response to external inputs have enabled smart sensors to live cell imaging. We report for the first time the development of a dynamic DNA nanomachine that is anchored on a cell's surface and undergoes pH-responsive triplex-duplex conformation switching, allowing tunable sensing and imaging of extracellular pH. Results reveal that the DNA nanomachine can be stably anchored on the cell surface via multiple anchors, and the adjustment of C + G-C content in the switch element confers tunability of pH response windows. The anchored DNA nanomachine also demonstrates desirable sensitivity, excellent reversibility, and quantitative ability for extracellular pH detection and imaging. This cell surface-anchored pH-responsive DNA nanomachine can provide a useful platform for pH sensing in extracellular microenvironments and diagnostics of different pH-related diseases.

Two complementary synthetic manifestations leading to highly substituted 1-naphthol and 2-naphthol derivatives via Lewis acids catalyzed annulations of ynamides with acyl chlorides are described here. A one-pot synthesis of 4-amino-2-naphthol derivatives is accomplished via a ZnI 2 -catalyzed tandem Friedel-Crafts reaction sequence. While in the presence of Pd(0) catalyst, a [2 + 2] cycloaddition reaction of ynamides with monosubstituted ketenes that were generated from the dehydrohalogenation of suitable acyl chlorides leads to efficient formation of 3-aminocyclobutenones, which were subsequently modified to generate 3-amino-1-naphthols in excellent yields.

The human proto-oncogene neuroblastoma RAS ( NRAS) contains a guanine-rich sequence in the 5'-untranslated regions (5'-UTR) of the mRNA that could form an RNA G-quadruplex structure. This structure acts as a repressor for NRAS translation and could be a potential target for anticancer drugs. Our previous studies found an effective scaffold, the quindoline scaffold, for binding and stabilizing the DNA G-quadruplex structures. Here, on the basis of the previous studies and reported RNA-specific probes, a series of novel p-(methylthio)styryl substituted quindoline (MSQ) derivatives were designed, synthesized, and evaluated as NRAS RNA G-quadruplex ligands. Panels of experiments turned out that the introduction of p-(methylthio)styryl side chain could enhance the specific binding to the NRAS RNA G-quadruplex. One of the hits, 4a-10, showed strong stabilizing activity on the G-quadruplex and subsequently repressed NRAS's translation and inhibited tumor cells proliferation. Our finding provided a novel strategy to discover novel NRAS repressors by specifically binding to the RNA G-quadruplex in the 5'-UTR of mRNA.

Two enantiomeric pairs of new 3d-4f heterometallic clusters have been built from two enantiomer Schiff base derivatives, labeled as R-/ S-H 2 L, in situ obtained from the condensation reactions with o-vanillin and R-/ S-2-phenylglycinol. The formulas of the series clusters are [Mn 6 Ln 2 (μ 3 -OH) 4 (μ 4 -O)(Ac) 4 (H 2 O) 2 ( R-L) 6 ]·NO 3 ·OH (Ln = Dy (1R), Gd (2R)), [Mn 6 Ln 2 (μ 3 -OH) 4 (μ 4 -O)(Ac) 4 (H 2 O) 2 ( S-L) 6 ]·NO 3 ·OH (Ln = Dy (1S), Gd (2S)), whose crystal structures and magnetic properties have been characterized. Structural analysis indicated that the above clusters consisted of a [Mn 6 Ln 2 ] core, featuring a sandwich configuration. The results of magnetic measurements showed the presence of slow magnetic relaxation with the effective energy barrier of 14.85 K in two Dy derivatives under the condition of zero-dc field, while the significant magnetocaloric effect of Gd analogues was found in a wide temperature range.

Hybridization chain reaction (HCR) circuits are valuable approaches to monitor low-abundance mRNA, and current HCR is still subjected to issues such as limited amplification efficiency, compromised localization resolution, or complicated designs. We report a novel branched HCR (bHCR) circuit for efficient signal-amplified imaging of mRNA in living cells. The bHCR can be realized using a simplified design by hierarchically coupling two HCR circuits with two split initiator fragments of the secondary HCR circuit incorporated in the probes for the primary HCR circuit. The bHCR circuit enables one to generate a hyperbranched assembly seeded from a single target initiator, affording the potential for localizing single target molecules in live cells. In vitro assays show that bHCR offers very high amplification efficiency and specificity in single mismatch discrimination with a detection limit of 500 fM. Live cell studies reveal that bHCR displays intense fluorescence spots indicating mRNA localization in living cells with improved contrast. The bHCR method can provide a useful platform for low-abundance biomarker detection and imaging for cell biology and diagnostics.

High-throughput and sensitive detection of proteins are essential for clinical diagnostics and biomarker discovery. We develop a novel high-throughput, multiplexed, sensitive mass spectrometric (MS) immunoassay method, which utilizes antibody-modified phospholipid bilayer coated gold nanoparticles (PBL-AuNPs) as the detection label and antibody-immobilized magnetic beads as the capture reagent. This method enables magnetic enrichment of the PBL-AuNPs label specific to target protein, allowing sensitive surface enhanced laser desorption ionization (SELDI)-TOF MS detection of the protein via its specific label. AuNPs act as not only the support but also the matrix for the phospholipids in SELDI TOF MS detection. Moreover, with phospholipids with varying molecular weights as the encoded MS reporters, this method allows multiplexed detection of multiple proteins. With the use of a predefined phospholipids internal standard, this method also affords excellent reproducibility in protein quantification. We have demonstrated this method using the assays of two tumor biomarkers, and the results reveal that it provides a sensitive platform for multiplexed protein detection with detection limits in the picomolar ranges. This method may provide a useful platform for high-throughput and sensitive detection of protein biomarkers for clinical diagnostics.

A highly torquoselective process for simultaneous control of central and axial chirality by the annulation of terminally substituted ynamides with o-quinone methides is reported. In the presence of AlCl 3 , a sequence comprising a [2 + 2] cycloaddition followed by the torquoselective 4π-electrocyclic ring opening and 6π-electrocyclic ring closure leads to highly stereoselective formation of diastereoisomeric 4-amino-2H-chromenes. Terminally unsubstituted ynamides undergo AlCl 3 -catalyzed [4 + 2] cycloaddition with o-quinone methides providing 2-amino-4H-chromenes.

We present a metal-free [2 + 2 + 2] cycloaddition of ynamides with nitriles that enables highly efficient access to 2,4-diaminopyridines. This catalytic protocol is more environmentally friendly and allows for a concomitant construction of C-C and C-N bonds between ynamides and nitriles, exhibiting excellent chemoselectivity, regioselectivity, and wide functional groups tolerance.

A Sn(IV)-promoted annulation reaction of ynamides is described for the efficient synthesis of 3-substituted 2-aminochromones under mild conditions. This novel method allows for a concomitant construction of C-C and C-O bonds between ynamides and 2-methoxyaroyl chlorides by a tandem Friedel-Crafts acylation/oxo-Michael addition/elimination strategy.

We report the first experimental evidence for the generation of highly strained cis,trans-cycloheptadienones by electrocyclic ring opening of 4,5-fused cyclobutenamides. In the presence of AlCl3, the cyclobutenamides rearrange to [2.2.1]-bicyclic ketones; DFT calculations provide evidence for a mechanism involving torquoselective 4π-electrocyclic ring opening to a cis,trans-cycloheptadienone followed by a Nazarov-like recyclization and a 1,2-alkyl shift. Similarly, 4,6-fused cyclobutenamides undergo AlCl3-catalyzed rearrangements to [3.2.1]-bicyclic ketones through cis,trans-cyclooctadienone intermediates. The products can be further elaborated via facile cascade reactions to give complex tri- and tetracyclic molecules.

Electrocyclic ring opening of 4,6-fused cyclobutenamides 1 under thermal conditions leads to cis,trans-cyclooctadienones 2-E,E as transient intermediates, en route to 5,5-bicyclic products 3. Theoretical calculations predict that 4,5-fused cyclobutenamides should likewise undergo thermal ring opening, giving cis,trans-cycloheptadienones, but in this case conversion to 5,4-bicyclic products is thermodynamically disfavored, and these cyclobutenamides instead rearrange to vinyl cyclopentenones.

The ynamide functional group activates carbon-carbontriple bonds through an attached nitrogen atom that bears an electron-withdrawing group. As a result, the alkyne has both electrophilic and nucleophilic properties. Through the selection of the electron-withdrawing group attached to nitrogen, chemists can modulate the electronic properties and reactivity of ynamides, making these groups versatile synthetic building blocks. The reactions of ynamides also lead directly to nitrogen-containing products, which provides access to important structural motifs found in natural products and molecules of medicinal interest. Therefore, researchers have invested increasing time and research in the chemistry of ynamides in recent years. This Account surveys and assesses new organic transforma-tions involving ynamides developed in our laboratory and in others around the world. We showcase the synthetic power of ynamides for rapid assembly of complex molecular structures. Among the recent reports of ynamide transformations, ring-forming reactions provide a powerful tool for generating molecular complexity quickly. In addition to their synthetic utility, such reactions are mechanistically interesting. Therefore, we focus primarily on the cyclization chemistry of ynamides. This Account highlights ynamide reactions that are useful in the rapid synthesis of cyclic and polycyclic structural manifolds. We discuss the mechanisms active in the ring formations and describe representative examples that demonstrate the scope of these reactions and provide mechanistic insights. In this discussion, we feature examples of ynamide reactions involving radical cyclizations, ring-closing metathesis, transition metal and non-transition metal mediated cyclizations, cycloaddition reactions, and rearrangements. The transformations presented rapidly introduce structural complexity and include nitrogen within or in close proximity to a newly formed ring (or rings). Thus, ynamides have emerged as powerful synthons for nitrogen-containing heterocycles and nitrogen-substituted rings, and we hope this Account will promote continued interest in the chemistry of ynamides.

We describe here details of our investigations into Pd-catalyzed and thermal aza-Claisen-carbocyclizations of N-allyl ynamides to prepare a variety of α,β-unsaturated cyclopentenimines. The nature of the ynamide electron-withdrawing group and β-substituent plays critical roles in the success of this tandem cascade. With N-sulfonyl ynamides, the use of palladium catalysis is required, as facile 1,3-sulfonyl shifts dominate under thermal conditions. However, since no analogous 1,3-phosphoryl shift is operational, N-phosphoryl ynamides could be used to prepare similar cyclopentenimines under thermal conditions through zwitter ionic intermediates that undergo N-promoted H-shifts. Alternatively, by employing ynamides bearing tethered carbon nucleophiles, the zwitter ionic intermediates could be intercepted, giving rise rapidly to more complex fused bi- and tricyclic scaffolds.

A highly diastereoselective addition of lithiated ynamides to Ellman-Davis chiral imines is described. While additions of N-sulfonyl ynamides are highly stereoselective even without Lewis acids, the use of BF3-OEt2 completely reversed the stereoselectivity. In addition, oxazolidinone-substituted ynamides behaved differently and functioned better with BF3-OEt2, and the chirality of the oxazolidinone ring exerts no impact on the selectivity.

A cascade of Pd-catalyzed N-to-C allyl transfer-intramolecular ketenimine-[2 + 2] cycloadditions of N-allyl ynamides is described. This tandem sequence is highly stereoselective and the [2 + 2] cycloaddition could be rendered in a crossed or fused manner depending on alkene substitutions, leading to bridged and fused bicycloimines.

A series of carbocyclization cascades of allyl ketenimines initiated through a thermal aza-Claisen rearrangement of N-phosphoryl-N-allyl ynamides is described. Interceptions of the cationic intermediate via Meerwein-Wagner rearrangements and polyene-type cyclizations en route to fused bi- and tricyclic frameworks are featured.

Pallambins A (1) and B (2), two novel 19-nor-7,8-secolabdane diterpenoids with unprecedented tetracyclo[4.4.0(3,5).0(2,8)]decane skeletons, along with a pair of structurally related isomers, pallambins C (3) and D (4), were isolated from the Chinese liverwort Pallavicinia ambigua. Their structures with absolute configurations were determined by means of NMR, X-ray diffraction, and CD analyses. Their preliminary cytotoxicity to human cancer cells was also tested.

The enantioselective N-heterocyclic carbene-catalyzed formal [2 + 2] and [2 + 2 + 2] cycloaddition of ketenes and isothiocyanates were developed. Reaction with N-aryl isothiocyanates at room temperature favors the [2 + 2] cycloaddition, while reaction with N-benzoyl isothiocyanates at -40 °C favors the [2 + 2 + 2] cycloaddition.

A novel caged cis-clerodane diterpenoid, scaparvin A, possessing an unprecedented C-6/C-11 bond and a ketal ring, as well as four new cis-clerodane derivatives, scaparvins B-E, were isolated from the Chinese liverwort Scapania parva. Their absolute structures were elucidated by analysis of NMR and CD data coupled with electronic circular dichroism (ECD) calculations. It was proposed that an enzymatic intramolecular aldol reaction was the key step in the biogenetic pathway of scaparvin A.

The highly diastereo- and enantioselective synthesis of beta-trifluoromethyl-beta-lactones bearing two contiguous stereocenters was realized by chiral N-heterocyclic carbene-catalyzed formal cycloaddition reaction of alkyl(aryl)ketenes and trifluoromethyl ketones.

A theoretical analysis of the reactions of four N7-protonated purine bases with phenylnitrenium and 4-biphenylylnitrenium ions, both in the gas phase and in aqueous solution, is studied to elucidate the effect of protonated purines on the formation of C8 adducts in a series of complicated carcinogenic reactions. Based on this analysis, four important conclusions are drawn. (i) The mechanism of C8 adduct formation by the addition of arylnitrenium ions directly to C8 sites of nucleotide bases in DNA is still supported. (ii) The N7 protonation of purine bases will lower the rate constants of these carcinogenic reactions, which agrees with observations and proves the experimental presumption. (iii) More complicated arylnitrenium ions have more of an effect on the reduction in the rate constants of these reactions involving N7-protonated purine bases. (iv) The rate constant of the C8 deprotonation process becomes larger when N7-protonated purine bases are involved in these carcinogenic reactions.

Two novel rearranged oleanane-type triterpenes, dysoxyhainanin A ( 1) possessing a unique 1,3- cyclo-2,3- seco A ring with a formamido-containing appendage and dysoxyhainanin B ( 2) featuring an unprecedented 1,2-dinor-3,10:9,10- bisseco skeleton, were isolated from Dysoxylum hainanense. Dysoxyhainanin A ( 1) exhibited significant antibacterial activity against Gram-positive bacteria.

Walsucochins A (1) and B (2) with an unprecedented skeleton were isolated from Walsura cochinchinensis. Their structures including absolute configuration were elucidated by spectral methods. A biosynthetic pathway of 1 and 2 was postulated. Both 1 and 2 exhibited significant cell protecting activities against H2O2-induced PC12 cell damage.

Walsuronoid A (1), a limonoid featuring an unprecedented 3,4-peroxide-bridged A-seco skeleton, together with walsuronoids B (2) and C (3) possessing a rare 18(13-->14)-abeo-limonoid skeleton, was isolated from Walsura robusta. The structures were elucidated by spectroscopic analysis and chemical correlation, and that of 1 was confirmed by single-crystal X-ray diffraction. Biosynthetic pathway of 2 and 3 was proposed and was chemically mimicked. Compounds 1 and 2 showed weak antimalarial activity.

[reaction: see text] Four novel tetranortriterpenoids, xylogranatins A-D (1-4), with an unusual 9,10-seco skeleton were isolated from the seeds of a Chinese marine mangrove Xylocarpus granatum. Their structures were determined by spectroscopic and chemical means. Xylogranatin A (1) featured by a unique 1,9-oxygen bridge was confirmed by single-crystal X-ray diffraction, and xylogranatin D (4) with an unprecedented skeleton of C-30-C-9 linkage was postulated biogenetically from 3 via an alpha-hydroxyl ketone rearrangement and was chemically mimicked.

[structure: see text] Two novel tetranortriterpenoids, turrapubesins A (1) and B (2), representing the first examples of halogenated and maleimide-bearing limonoids, were isolated from the twigs and leaves of Turraea pubescens. The structures of 1 and 2 were elucidated by extensive spectroscopic analysis. Their absolute configurations were determined by X-ray crystallography of 1 and by CD analysis of a dihydrogenated derivative of 2. Turrapubesin A (1) exhibited weak cytotoxicity against the P-388 tumor cell line.