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Sulfonamides are important structures in pharmaceuticals, agrochemicals, and organocatalysts, yet the rapid and benign synthesis of these compounds is still a great challenge. Herein we report a photoinduced method for synthesizing sulfonamides from (hetero)aryl carboxylic acid oxime esters. This reaction proceeds via one-pot cascade radical-radical cross-coupling by energy-transfer-mediated photocatalysis. A wide substrate scope including (hetero)aryl substrates and late-stage modification of pharmaceutical molecular entities reveal its generality.

Here, we have constructed five distinct types of N -acyl or N -sulfonyl aza-sulfur scaffolds using readily available (sulfon)amides and thiophthalimides with precise regulation of oxidants. Our novel methods feature one-pot mild reaction conditions and simple operation, thereby making them highly convenient for the late-stage diversification of various amide drugs, bioactive molecules, and peptides.

A Rh(III)-catalyzed C-H bond activation for the synthesis of fused 2 H -isoindole scaffolds from oxadiazolones with diazo compounds was developed. The reaction proceeded through C-H activation of oxadiazolones/[4 + 1] annulation, intramolecular cyclization, and an unusual acyl migration cascade to afford target scaffolds with good yields. These 2 H -isoindole derivatives could be further transformed into intriguing drug privileged scaffolds.

Here, we report a novel strategy for constructing maleimide-containing peptides and cyclic peptides using Rh(III)-catalyzed tryptophan (Trp) (C7) alkenylation, which is challenging due to the inherent reactivity of the indole benzenoid ring. This method is scalable and exhibits broad substrate scope. The utility of this protocol could further be demonstrated by the synthesis of peptide conjugates with natural products and amino acids as well as the construction of maleimide-braced cyclic peptides.

A Rh(III)-catalyzed C-H activation of α-keto oximes and a cyclization cascade with diazo compounds were developed to construct the highly fused indano[1,2- b ]azirine frameworks in good yields with a broad range of substrates under mild reaction conditions. More intriguingly, a [4+1+1] sequential annulation cascade is demonstrated for the first time in this reaction and opened a new reaction mode for α-keto oximes. These fused indano[1,2- b ]azirine derivatives could also be further transformed into intriguing privileged drug scaffolds.

A novel diterpenoid, sinunanolobatone A ( 1 ), featuring an unprecedented bicyclo[13.1.0]pentadecane carbon framework, along with two new casbane diterpenoids ( 2 and 3 ), and five known related ones ( 4 - 8 ) were isolated from the Sanya soft coral Sinularia nanolobata . The structures of the new compounds were established by detailed spectroscopic analysis, X-ray diffraction analysis, chemical reactions, or a quantum chemical computation method. A plausible biosynthetic pathway of 1 was proposed. In bioassay, the novel compound 1 showed significant inhibitory activity against lipopolysaccharide (LPS) induced inflammation in BV-2 microglial cells.

A novel norditerpenoid, sinusiaetone A ( 1 ), featuring an uncommon bicyclo[11.3.0]hexadecane carbon skeleton, and four polyoxygenated cembranoids ( 2-5 ) were isolated from the Hainan soft coral Sinularia siaesensis . Their structures were established by spectroscopic analysis, X-ray diffraction, quantum chemical computational approaches, and/or a modified Mosher's method. A plausible biosynthetic pathway of 1 and its biogenetic relationship with 2-5 were proposed. New compounds 1-3 displayed an interesting inhibitory activity against lipopolysaccharide-induced inflammation in BV-2 microglial cells.

An efficient regioselective palladium(II)-catalyzed C(sp 2 )-H 4-acetoxylation of tryptophan and tryptophan-containing peptides is described. This transformation achieves the direct construction of C-O bonds at the tryptophan C4-position and features good functional group tolerance. The 4-hydroxyl compound was obtained by removing acetyl after C4-acetoxylation of tryptophan derivatives and tryptophan-containing dipeptides. This method provides a novel strategy for the synthesis of 4-substituted tryptophan derivatives and modification of tryptophan-containing peptides.

Two new macrocyclic cembranoids were isolated from the South China Sea soft coral Lobophytum sp. Quantum mechanical-nuclear magnetic resonance (QM-NMR) methods were decisive in their structural elucidation. Better performance in arriving at definitive structures was obtained by QM-NMR methods upon incorporation of 3 J HH values. The validity of this approach also supported an alternative conformational proposal versus that obtained by X-ray crystallography.

Maleimide is widely applied in many fields, especially in antibody-drug conjugations and peptide drugs. Herein, we develop a strategy for the C-H alkenylation of tryptophan and tryptophan-containing peptides, providing a synthetic route of decorating maleimide on peptides. The method has a high tolerance of functional groups and protecting groups. Furthermore, this method was applied to prepare peptide conjugation with molecules such as drugs and fluorescence probes. Moreover, macrocyclic peptides were obtained via this reaction.

Herein, we report a novel stepwise addition-controlled ring size method, to access tetrahydropyrimidines through an operationally simple [3 + 3] cycloaddition of vinylethylene carbonates with triazinanes. Interestingly, we could also use this method for a [3 + 3] oxidative cycloaddition, which allows the facile synthesis of polysubstituted terphenyls under mild conditions. Mechanistic studies suggest that vinylethylene carbonates could generate α,β-unsaturated aldehydes as 3-carbon synthons for cycloaddition via a combination process of Pd-catalyzed decarboxylation and β-H elimination.

Two novel polyoxygenated diterpenoids, klyflaccilides A ( 1 ) and B ( 2 ), featuring an uncommon 6/5/8/3 tetracyclic ring system, were isolated from the Hainan soft coral Klyxum flaccidum . Their structures were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or a quantum chemical computation method. A plausible biosynthetic relationship of 1 and 2 with their potential precursor 3 was further proposed. Compounds 1 and 3 exhibited moderate anti-inflammatory activity by the inhibition of LPS-induced TNF-α protein release.

One formidable challenge in sp 2 C-H activation is how to achieve high para selectivity on electron-deficient arenes because such site selectivity is disfavored by the electronic bias induced by the electron-withdrawing groups. The first highly selective para-C-H acetoxylation of various benzoic acids using a nitrile-based template was realized. Removal of the template leads to para-hydroxylated benzoic acids, which are versatile intermediates for a wide range of synthetically useful transformations.

In the present study, a novel synthetic strategy to directly produce versatile 3-acylindoles through Rh(III)-catalyzed C-H activation and annulation cascade of N-phenylamidines with α-Cl ketones was developed, in which α-Cl ketones serve as unusual one-carbon (sp 3 ) synthons. This strategy features high regioselectivity, efficiency, wide substrate tolerance, and mild reaction conditions, which further underscore its synthetic utility in drug molecule synthesis.

Two novel nitrogenous diterpenoids, sarinfacetamides A (1) and B (2), featuring an uncommon tricyclo[6.3.1.0 1,5 ]dodecane scaffold, and a known related diterpene (3) were isolated from the South China Sea soft coral Sarcophyton infundibuliforme. Their structures, including the absolute configuration of 1, were established by extensive spectroscopic analysis and TDDFT-ECD calculation. Compounds 1 and 3 exhibited interesting promotion effects on the ConA-induced T lymphocyte proliferation. A plausible biosynthetic pathway for 1 and 2 was also proposed.

Rh (III)-catalyzed C-H activation of benzoylacetonitriles in coupling with diazo compounds was developed to synthesize diversified substituted benzo[ de]chromenes via a formal (4 + 2) cycloaddition with a diazo compound and subsequent tandem (4 + 2) cycloaddition with another diazo compound. Intriguingly, synthesis of substituted benzo[ de]chromenes and their decarboxylation products could be realized by controlling the reaction conditions. These reactions have a broad range of substrates, moderate to good yields, and high regioselectivity.

Here we report an aerobic Pd(0) catalyzed C2-H functionalization of indoles and pyrroles with tethered N-methoxylamide as the directing group. A Pd(0)-initiated mechanism overcomes the directing or poisoning effect from a wide range of heterocycles including pyridine, pyrimidine, and thiazole. The imidazo[1,5-a]indole products are transformed to bioactive analogs after one-step manipulations, demonstrating the potential utility of this reaction in drug discovery.

Three new diterpenes, xishacorenes A-C, featuring an undescribed bicyclo[3.3.1]nonane nucleus bearing 1-vinyl and 13-[(E)-4-methylpenta-1,3-dien-1-yl] alkyl chains, and a related monocyclic known compound, were isolated from the Xisha soft coral Sinularia polydactyla. The structures of xishacorenes A-C, including their absolute configurations, were elucidated by extensive spectroscopic analysis and TDDFT ECD calculations. The new compounds exhibit an interesting dose-dependent promotion effect on the ConA-induced T lymphocyte proliferation. A plausible biosynthetic pathway of xishacorenes A-C is proposed.

Four limonoids, triconoids A-C (1-3) possessing a new rearranged mexicanolide skeleton and triconoid D (4) furnishing a new rearranged 1,2-seco-phragmalin skeleton, were isolated from the Nepalese plant Trichilia connaroides. Two rearranged limonoid skeletons sharing an F ring of methyl 5-oxotetrahydrofuran-2-carboxylate were postulated to be formed biosynthetically via a very unique chemical cascade. Their structures were fully accomplished by spectroscopic data, single-crystal X-ray diffraction, and electrostatic circular dichroism analysis.

Herein, rhodium(III)-catalyzed C-H activation/subsequent [4 + 1] cyclization reactions between benzamides and propargyl alcohols are reported in which propargyl alcohols serve as unusual one-carbon units. This title transformation led to a series of isoindolinones bearing a quaternary carbon with moderate to good yields without the requirement for external metal oxidants. Due to the mild and simple reaction conditions, this reaction is compatible with various functional groups.

The first total synthesis of a marine derived polyacetylene, distaminolyne A, and its enantiomer were achieved from the commercially available undec-10-en-1-ol. A key proline-catalyzed asymmetric α-aminooxylation of an aldehyde intermediate was used to introduce the chiral center en route to the enantiomerically pure 1,2-amino alcohols. The absolute configuration of both synthesized enantiomers of distaminolyne A was confirmed by using chiral derivatizing agents, leading to revision of the natural product absolute configuration from 2S to 2R. Antibacterial, pancreatic lipase (PL) inhibitory, and protein-tyrosine phosphatase 1B (PTP1B) inhibitory activities were evaluated.

In this study we developed a method for the pyridine-directed, rhodium-catalyzed, site-selective C-H alkylation and arylation of pyridones using commercially available trifluoroborate reagents. This simple and versatile transformation proceeded smoothly under relatively mild conditions with perfect site selectivity. The coupling groups in the boron reagents can be extended to primary alkyl, benzyl, and cycloalkyl. Moreover, direct C-H arylation products could also be obtained under similar conditions.

Chemical investigation into the alkaloidal constituents of the Nepalese Daphniphyllum himalense has returned two new compounds, himalensines A (1) and B (2), with unprecedented carbon skeletons. Structures of the two alkaloids have been characterized on the basis of spectroscopic methods, especially via 2D NMR data analysis. Himalensine B (2) showed marginal inhibitory activities against two kinases, PTP1B and IKK-β.

Two new alkaloids, flueggether A (1) and virosinine A (2), were isolated from a Chinese medicinal plant, Flueggea virosa. Their structures were assigned via spectroscopic methods with the absolute configurations of 1 and 2 being established by X-ray diffraction analysis and calculated electronic circular dichroism data, respectively. Compound 1 represents the first example with an ether bridge of Securinega alkaloid oligomers, and 2 bears a new heterocyclic backbone. Both alkaloids showed mild in vitro anti-HIV activity.

A phase transfer reagent promoted tandem ring-opening and ring-closing reaction of 3-(1-alkynyl) chromones has been developed. This process remarkably generates functionalized 3-acyl-2-substituted chromones. Interestingly, when 3-(hepta-1,6-diyn-1-yl)chromone derivatives are applied, a novel tetracyclic chromone scaffold can be obtained by a further intramolecular 4 + 2 cyclization.

A Rh(III)-catalyzed intramolecular redox-neutral or oxidative annulation of a tethered alkyne has been developed to efficiently construct 3,4-fused indoles via a C-H activation pathway. The advantages of this process are (1) ready availability of annulation precursors; (2) broad substrate scope; (3) complete regioselectivity; (4) simple and mild reaction conditions; and (5) no need for an external oxidant or to employ molecular oxygen as the stoichiometric terminal oxidant.

An exoselective copper-catalyzed arylation- and vinylation-carbocyclization of electron-deficient alkenes was developed to provide rapid and efficient access to a variety of functionalized 3,3-disubstituted oxindoles. With this method, a highly efficient and concise formal synthesis of (±)-physostigmine and (±)-physovenine has been completed.

An unprecedented Rh(III)-catalyzed direct intermolecular C-H amidation with N-hydroxycarbamates has been developed. Different directing groups, such as pyridine, pyrimidine, pyrazole, and N-OMe oxime, can be employed in this C-H amidation process, providing valuable N-carbamate-protected arylamines (e.g., Cbz, Moz, Ac, Boc, and Fmoc). More importantly, this process may afford a new avenue for intermolecular C-H amidation where readily available N-hydroxycarbamates can be used as the nitrogen source.

An unprecedented Rh-catalyzed direct addition of aryl C-H bonds to nitrosobenzenes has been developed under very mild reaction conditions (room temperature). The reaction is highly step-, atom-, and redox-economic and compatible with air and water to N-selectively provide a variety of N-diarylhydroxylamines in good to excellent yields. More importantly, this process may provide a new direction for C-N bond formation through direct C(sp(2))-H functionalization.

A Rh(III)-catalyzed direct aldehyde C-H amidation from aldehydes and N-chloroamines, prepared in situ from amines, has been developed via C-H bond activation under very mild reaction conditions. A variety of primary and secondary amines were used to afford the corresponding amides in moderate to excellent yields.

The rhodium-catalyzed addition of an alkenyl C-H bond to isocyanates via sp(2) C-H bond activation followed by an intramolecular cyclization is described. This atom-economic and catalytic reaction affords a simple and straightforward access to biologically relevant 5-ylidene pyrrol-2(5H)-ones and can be carried out under mild and neutral conditions in the absence of any additives and environmentally hazardous waste production.

Methyl sarcotroates A and B (3 and 4), two unprecedented diterpenoids possessing a tetradecahydrocyclopenta[3',4']cyclobuta[1',2':4,5]cyclonona[1,2-b]oxirene ring system, along with their probable biogenetic precursor, sarcophytonolide M (1), were isolated from the Hainan soft coral Sarcophyton trocheliophorum. Their structures were elucidated by detailed spectroscopic analysis, and the absolute configuration of compound 3 was determined by TDDFT ECD calculations. Compound 4 exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), being similar to that of positive control oleanolic acid.

Serratustones A (1) and B (2), featuring a new carbon skeleton and representing a novel dimerization pattern of two different types of sesquiterpenoids, were isolated from Chloranthus serratus. Their structures with absolute configuration were determined on the basis of a detailed explanation of spectroscopic data, X-ray crystallography, and CD analysis in combination with ECD calculation.

An enantioselective synthesis of (-)-(α)-kainic acid in 15 steps with an overall yield of 24% is reported. The pyrrolidine kainoid precursor with the required C2/C3 trans stereochemistry was prepared with complete diastereoselectivity via an unprecedented SmI2-catalyzed intramolecular [3 + 2] cycloaddition reaction of an aryl cyclopropyl ketone and an alkyne. Double bond isomerization was then employed to set the remaining stereochemistry at the C4 position en route to (-)-(α)-kainic acid.

A novel cascade reaction was developed for the synthesis of diverse members of a series of benzofuro[3,2-d]pyrimidine derivatives. The process utilizes readily prepared 3-chlorochromenones and various commercially available amidines and their analogues as starting materials. This tandem reaction is promoted by using a simple copper(I) reagent and involves a chemoselective Michael addition-heterocyclization-intramolecular cyclization sequence.

Two unprecedented dimeric diterpenoids, with a 2,3-dihydrofuran ring fusing an abietane and a 4,5-seco-abietane diterpene, were isolated from Cunninghamia lanceolata. Their structures were elucidated by spectroscopic measurements, and their absolute configurations were determined by quantum chemical TDDFT ECD calculations, chemical transformations, and Mosher's method. The Mosher method carried out with MPA and MTPA esters of the sterically hindered sec-hydroxyl group gave contradictory results, while MPA afforded the correct absolute configuration., (© 2011 American Chemical Society)

A novel α-alkylbutenolide dimer, paracaseolide A (2), characterized by an unusual tetraquinane oxa-cage bislactone skeleton bearing two linear alkyl chains, was isolated from the mangrove plant Sonneratia paracaseolaris. The structure of 2 was elucidated by extensive spectroscopic analysis. A plausible retrosynthetic pathway for paracaseolide A (2) was proposed. Compound 2 exhibited significant inhibitory activity against dual specificity phosphatase CDC25B, a key enzyme for cell cycle progression, with an IC(50) value of 6.44 μM., (© 2011 American Chemical Society)

Two new limonoids, namely aphanamolides A (1) and B (2), were isolated from the seeds of Aphanamixis polystachya . Their structures were established by spectroscopic methods. Aphanamolide A (1) featured an unprecedented carbon skeleton via the formation of a C-3-C-6 bond. Compounds 1 and 2 showed cytotoxic activity against two tumor cell lines.

An efficient tandem process was developed to synthesize diversified benzo[a]xanthones from 2-methyl-3-(1-alkynyl)chromones with electron-deficient chromone-fused dienes. This unusual reaction, involving multiple steps and not requiring the use of transition metal catalysts or an inert atmosphere, results in the formation of three new C-C bonds and one C-O bond.

A novel base-promoted cascade reaction of 2-methyl-3-(1-alkynyl)chromones to produce a 3C-xanthone-linked 3C-chromone scaffold has been developed. This tandem process involves multiple reactions such as Michael additions/cyclizations under mild conditions without a transition metal catalyst and inert atmosphere.

[structure: see text] Chlorahololides A(1) and B(2), two highly complex sesquiterpenoid dimers, were isolated from Chloranthus holostegius. Their structures and absolute configurations were established by NMR spectroscopy, X-ray crystallography, and CD. Chlorahololides A (1) and B (2) exhibited potent and selective inhibition on the delayed rectifier (IK) K+ current, with an IC50 of 10.9 and 18.6 microM, respectively.

[structure: see text] The first diamino Daphniphyllum alkaloid, daphnipaxinin (1), with an unprecedented hexacyclic fused skeleton, along with a known alkaloid, daphnicyclidin A (2), was isolated from the stem of Daphniphyllum paxianum Rosenth. The structure and absolute stereochemistry of 1 were established by spectral methods, especially two-dimensional NMR techniques and CD analysis.