Search

Lancilactone C is a tricyclic triterpenoid that inhibits human immunodeficiency virus (HIV) replication in H9 lymphocytes with no cytotoxicity. Its tricyclic skeleton comprises trans-dimethylbicyclo[4.3.0]nonane and 7-isopropylenecyclohepta-1, 3, 5-triene. The latter unique structure, in which all carbon atoms are sp2 hybridized, is not found in other triterpenoids and needs to be verified synthetically. Herein, we have accomplished the first total synthesis of lancilactone C (proposed structure) by developing a new domino [4 + 3] cycloaddition reaction involving oxidation, Diels–Alder reaction, elimination, and electrocyclization. We have also revised the structure based on the total synthesis of lancilactone C according to its plausible biosynthetic pathway., ランシラクトンCの全合成と構造改訂 --ペリ環状反応を駆使して--. 京都大学プレスリリース. 2023-06-22.

Poly(amidoamine) (PAMAM) dendrimers are used to modify the interface of metal-semiconductor junctions. The large number of protonated amines contributes to the formation of a dipole layer, which finally serves to form electron selective contacts in silicon heterojunction solar cells. By modifying the work function of the contacts, the addition of the PAMAM dendrimer interlayer quenches Fermi level pinning, thus creating an ohmic contact between the metal and the semiconductor. This is supported by the observation of a low contact resistivity of 4.5 mΩ cm2, the shift in work function, and the n-type behavior of PAMAM dendrimer films on the surface of crystalline silicon. A silicon heterojunction solar cell containing the PAMAM dendrimer interlayer is presented, which achieved a power conversion efficiency of 14.5%, an increase of 8.3% over the reference device without the dipole interlayer.

Proton-coupled electron transfer (PCET) is a ubiquitous and fundamental process in biochemistry and electrochemistry performed by transition-metal complexes. Most synthetic efforts have been devoted to selecting the components, that is, metal ions and ligands, to control the proton–electron coupling. Here, we show the first example of controlling the proton–electron coupling using the cis–trans metal–ligand isomerization in a π-planar platinum complex, Pt(itsq)₂ (itsq¹⁻: o-iminothiosemiquinonate). Both the isomers, which were obtained separately, were characterized by single-crystal X-ray diffraction, and the cis-to-trans isomerization was achieved by immersing in organic solvents. Theoretical calculations predicted that the proton–electron coupling evaluated from the energetic stabilization of the lowest unoccupied molecular orbital by protonation varies greatly depending on the geometrical configuration compared to the metal substitution.

Presented herein is a controllable selective construction of spiro or fused heterocyclic scaffolds through the one-pot cascade reactions of 1-phenylpyrazolidinones with maleimides. To be specific, succinimide spiro pyrazolo[1,2

A cooperative tertiary amine/palladium-catalyzed sequential reaction process, proceeding via a [4 + 3] cyclization of isatin-derived Morita-Baylis-Hillman Expansion (MBH) carbonates and

An asymmetric catalytic approach for the construction of C3-multifunctionalization α-hydroxy-β-amino pyridines has been reported. The products can be accessed by the modulation of two chiral catalysts independently in high yield and with good enantioselectivity. The method features mild reaction conditions and an excellent functional group tolerance. Biological activity analysis shows that the resulting products have a selective antiosteosarcoma activity on 143B cells.

The stereochemistry of the lipophilic side chain of (+)-rakicidin F had not been determined until recently. Using our lithiation-borylation methodology ("assembly line synthesis") we were able to efficiently prepare the all-syn isomer as well as the C-21 epimer of the side chain, and comparison with the natural product suggested that the natural product had all-syn stereochemistry. Completion of the total synthesis using a macrolactamization of the northern amide enabled us to confirm Wang and Chen's stereochemical findings for the structure of (+)-rakicidin F.

Asymmetric total synthesis of neobraclactone C was finished for the first time using the convergent synthetic strategy in 22 steps in the longest linear sequence from known materials. The key steps include a steric hindrance/hydrogen bond dual-controlled Heck arylation of α,β-unsaturated ketone to construct hemiketal and

A convenient method was developed for the preparation of thiolated compounds

An approach for the copper-catalyzed synthesis of enantioenriched amides bearing an α-stereogenic center is disclosed. This method involves the addition of an allyl copper species to an isocyanate and allows access to α-substituted chiral amides in high yields and high-to-excellent enantioselectivities. The utility of α-vinyl β-boryl amides in synthesis is highlighted by the diversification of products to afford highly useful scaffolds. DFT calculations reveal that the catalyst preferentially coordinates to the oxygen of the isocyanate. Enantiocontrol arises from the steric repulsion between the boryl group and the stereodirecting phenyl of the chiral ligand.

Chlorinated malonic acid half thioesters were established as chloroacetate surrogates and used in stereoselective organocatalyzed decarboxylative aldol-type additions. Enantioenriched alpha-chloro-beta-hydroxy thioesters were obtained under mild reaction conditions in high yields and allowed for diverse derivatization as highlighted by the synthesis of (+)-prebalamide and (+)-norbalasubramide analogs. ISSN:1523-7060 ISSN:1523-7052

The synthesis of bromo-substituted indeno[1,2

The first copper-catalyzed enantioselective [4 + 1] annulation of yne-allylic esters with 1,3-dicarbonyl compounds was realized through an elegant remote stereocontrol strategy. The very remote ε regioselective nucleophilic substitution was developed by employing a novel chiral copper-vinylvinylidene species from the new C4 synthon yne-allylic esters. Thus, greatly diverse spirocycles were obtained with ample scope and excellent levels of chemo-, regio-, and enantioselectivities. Moreover, detailed mechanistic studies suggest an yne-allylic substitution and Conia-ene cascade pathway on the remote stereochemical induction progress.

The total synthesis of raistrickindole A has been achieved, thereby confirming the proposed structure as an N-hydroxylated DKP. In the first but less selective approach, the DKP was built up by cyclization of a diastereoisomerically mixed N-hydroxylated dipeptide. In the second approach, the same DKP was constructed stereoselectively by the intramolecular Mitsunobu reaction of a hydroxamic acid. The synthesis was completed by a stereoselective oxidative cyclization. Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version We thank NTU for financial support of this work. This research was partially supported by the National Research Foundation (NRF) Singapore, NRF Competitive Research Programme (CRP), Grant Award Number NRF-CRP18-2017-01.

Herein, a novel [Rh]

We developed a visible-light-mediated [3 + 2] cycloaddition of arylcyclopropylamine with structurally diverse olefins using

In this study, a framework for the prediction of thermophysical properties based on transfer learning from existing estimation models is explored. The predictive capabilities of conventional group-contribution methods and traditional machine-learning approaches rely heavily on the availability of experimental datasets and their uncertainty. Through the use of a pretraining scheme, which leverages the knowledge established by other estimation methods, improved prediction models for thermophysical properties can be obtained after fine-tuning networks with more accurate experimental data. As our experiments show, for the case of critical properties of compounds, this pipeline not only improves the performance of the models on commonly found organic structures but can also help these models generalize to less explored areas of chemical space, where experimental data is scarce, such as inorganics and heavier organic compounds. Transfer learning from estimation models data also allows for graph-based deep learning models to create more flexible molecular features over a bigger chemical space, which leads to improved predictive capabilities and can give insights into the relationship between molecular structures and thermophysical properties. The generated molecular features can discriminate behavior discrepancy between isomers without the need of additional parameters. Also, this approach shows better robustness to outliers in experimental datasets.

We report a 1,2-migration (aryl dance reaction) of the aryl group on heteroles. AlCl

Rapid and efficient access to structurally diverse β-fluoroalkylamines is in high demand, with their wide presence and great importance in medicinal chemistry and drug development. Direct 1,2-aminofluorination of alkenes offers an ideal strategy for one-step entry to β-fluorinated amines from readily available starting materials. Yet the synthesis of valuable β-fluorinated alkylamines remains an unsolved challenge, due to the inherent incompatibility between electrophilic fluoride sources and the electron-rich alkylamines. We report an unprecedented, catalytic, three-component aminofluorination of diverse alkenes and 1,3-dienes, which has been achieved by an innovative copper-catalyzed electrophilic amination strategy using O-benzoylhydroxylamines as alkylamine precursors. The use of Et(3)N•3HF is also critical, not only as a commercially available and inexpensive fluoride source to enable effective fluorination but also as an acid source for the formation of aminyl radical cation for electrophilic amination. Mechanistic experiments suggest the involvement of aminyl radical species and carbon-radical intermediates under reaction conditions. This method features high regioselectivity, good tolerance of diverse functional groups, and provides a practical and direct entry to a broad range of β-fluorinated electron-rich alkylamines. Synthetic applications of this method have also been highlighted by its use for the rapid entry to β-fluoridated amine-containing pharmaceuticals, natural products, and bioactive compounds.

The structural properties of the polyethylenimine (PEI) polymer are generally tuned and selectively modified to reinforce its potential in a broad spectrum of applied domains of medicine, healthcare, material design, sensing, and electronic optimization. The selective modification of the polymer brings about changes in its interfacial characteristics and behavior. The current work involves the synthesis of naphthalimide conjugated polyethylenimine organic nanoparticles (NPEI-ONPs). The interfacial molecular structure of NPEI-ONPs is explored in an aqueous medium at pH 7.4 using surface tensiometry and sum-frequency generation vibrational spectroscopy (SFG-VS). The hydrophobic functionalization rendered a concentration-dependent surface coverage of NPEI-ONPs, where the SFG-VS analysis exhibited the molecular rearrangement of its hydrophobic groups at the interface. The interaction of NPEI-ONPs with double-stranded DNA (dsDNA) is carried out to observe the relevance of the synthesized nanocomposites in the biomedical domain. The bulk-specific studies (i.e., thermal denaturation, viscometry, zeta (ζ) potential, and ATR-FTIR) reveal the condensation of dsDNA in the presence of NPEI-ONPs, making its structure more compact. The interface-sensitive SFG-VS showcased the impact of the dsDNA and NPEI-ONP interaction on the interfacial molecular behavior of NPEI-ONPs at the air-aqueous interface. Our results exhibit the potential of such hydrophobically functionalized ONPs as promising candidates for developing biomedical sealants, substrate coatings, and other biomedical domains.

Chiral fluorinated amino esters and pyrrolidines are privileged scaffolds in synthetic chemistry and exhibit unique biological properties. We report the facile preparation of these compounds through copper-catalyzed switchable defluoroalkylation and [3 + 2] cycloaddition of trifluoropropene in an asymmetric fashion. The choice of solvent and chiral ligand was crucial for the efficient transformation and exquisite chemoselectivity pattern from identical starting materials that rapidly and reliably incorporate

Rhodium-catalyzed enantioselective synthesis of 1-phenoxycyclopropane-1-carbaldehydes by intermolecular cyclopropanation of terminal alkenes followed by imine hydrolysis is described. This methodology utilizes 4-aryloxy-1-sulfonyl-1,2,3-triazoles as the carbene precursors and the chiral dirhodium(II) tetracarboxylates Rh

It has been recently suggested that diametral (so-called quality) similarity thresholds are superior to radial ones for the clustering of molecular three-dimensional structures. 1 The argument has been made for two clustering algorithms available in various software packages for the analysis of molecular structures from ensembles generated by computer simulations, attributed to Daura et al. 2,3 (radial threshold) and Heyer et al. 4 (diametral threshold). Here, we compare these two algorithms using the root-mean-squared-difference between the Cartesian coordinates of selected atoms as pairwise similarity metric. We discuss formally the relation between these two methods and illustrate their behavior with two examples, a set of points in two dimensions and the coordinates of the tau polypeptide along a trajectory extracted from a replica-exchange molecular-dynamics simulation. 1,5 We show that the two methods produce equally-sized clusters as long as adequate choices are made for the respective thresholds. The real issue is not whether the threshold is radial or diametral, but how to choose in either case a threshold value that is physically meaningful. We will argue that, when clustering molecular structures with the RMSD as metric, the simplest best guess for a threshold is actually radial in nature.

Photocatalytic dehydrogenative [2 + 2] cycloadditions between amines and alkenes were developed that allow for the stereoselective and high-yielding synthesis of functionalized azetidines. The oxidative formal Aza Paternò-Büchi reactions are induced by photoredox-catalyzed aerobic oxidation of dihydroquinoxalinones

In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD

Herein, we report a highly efficient and unprecedented approach for heteroarylation of congested α-bromoamides via electrophilic aromatic substitution of imidazo-heteroarenes and indolizines under mild reaction conditions (room temperature, metal, and oxidant free). The participation of an in situ generated aza-oxyallyl cation as an alkylating agent is the hallmark of this transformation. The method was readily adapted to synthesize novel imidazo-heteroarene-fused dibenzoazepinone architectures of potential medicinal value.

Nordine was reported to be an unusual humulene-type macrocyclic sesquiterpenoid that contains an ether-bridged bicyclic ring between C-10 and C-6 with a hydroxy group at position 2. Here, we report the structure revision of nordine based on incongruities found for carbon chemical shifts in the originally proposed structure, in addition to formation of a diacetylated derivative. As expected, a single-crystal X-ray diffraction analysis unambiguously confirmed our proposal that the nordine (

The dialkyl-ortho-biaryl class of phosphines, commonly known as Buchwald-type ligands, are among the most important phosphines in Pd-catalyzed cross-coupling catalysis. These ligands have also been successfully applied to several synthetically valuable Ni-catalyzed cross-coupling methodologies, and as demonstrated in this work, are top performing ligands in Ni-catalyzed Suzuki Miyaura Coupling (SMC) and C–N coupling reactions, even outperforming commonly employed bisphosphines like dppf in many circumstances. However, little is known about their structure-reactivity relationships (SRRs) with Ni, and limited examples of well-defined, catalytically relevant Ni complexes with Buchwald-type ligands exist. In this work, we report the analysis of Buchwald-type phosphine SRRs in four representative Ni-catalyzed cross-coupling reactions. Our study was guided by data-driven classification analysis, which together with mechanistic organometallic studies of structurally characterized Ni(0), Ni(I), and Ni(II) complexes allowed us to rationalize reactivity patterns in catalysis. Overall, we expect that this study will serve as a platform for further exploration of this ligand class in organonickel chemistry, as well as in the development of new Ni-catalyzed cross-coupling methodologies.

A Pd/phase-transfer catalyst cooperatively catalyzed domino Heck/allylation reaction is first reported, which represents interesting substrate-dependent regioselectivity. Under the same conditions, Ts-protected

(-)-Ceforalide B (b1/b) and (-)-cephanolides B-D (b2/b-b4/b) are benzenoid cephanolide diterpenoids possessing the same pentacyclic skeleton, which contains three Csub13/sub-Csub15/subsubstituent patterns and different benzylic oxidation states. An olefination/6π-electrocyclization/oxidative aromatization cascade has been verified as divergent access to three Csub13/sub-Csub15/subpatterns. The benzylic aerobic oxidations enabled by the Co(OAc)sub2/sub·4Hsub2/subO/bromide salt/Osub2/sub/PPhsub3/sub/iN/i-hydroxyphthalimide system have been developed to deliver expected site-selectivity and different oxidation states. Through the divergent strategy, total synthesis of (-)-ceforalide B and (-)-cephanolides B-D is accomplished.

To develop highly efficient and low cost acaricides, a series of 2,4-diphenyl-1,3-oxazolines containing an ether moiety at the

A mild and eco-friendly visible-light-mediated regioselective C-H alkoxycarbonylation of imidazo[1,2

Fe(II) and Ni(II) paraCEST contrast agents containing the di-pyridine macrocyclic ligand 2,2',2″-(3,7,10-triaza-1,5(2,6)-dipyridinacycloundecaphane-3,7,10-triyl)triacetamide (DETA) are reported here. Both [Fe(DETA)]

An (N-heterocyclic carbene)nickel(I) cation precursor reacts with the corresponding nickel(0) complex to form a dinickel(I,0) monocation. The Ni···Ni distance in this cation is 0.93 Å shorter than in the analogous dinickel(0) complex. Although the solid-state structure shows equivalent Ni centers, density functional theory calculations indicate significant electronic localization. Reactions with CO and NO form mononuclear carbonyl and nitrosyl complexes. Oxidative addition of an aryl bromide results in

A pharmacophore-directed retrosynthetic (PDR) strategy was applied to the first total synthesis of the cembranoid, rameswaralide, in order to simultaneously achieve a total synthesis while also developing a structure-activity relationship profile throughout the synthetic effort. The synthesis utilized a Diels-Alder-Lactonization, including a rare kinetic resolution to demonstrate the potential of this strategy for an enantioselective synthesis providing both 5,5,6- and, through a ring expansion, the 5,5,7-tricyclic ring systems present in several Sinularia soft coral cembranoids. A pivotal synthetic intermediate, a tricyclic epoxy α-bromo cycloheptenone, displayed high cytotoxicity with interesting selectivity toward the HCT-116 colon cancer cell line. This intermediate enabled the pursuit of three unique D-ring annulation strategies including a photocatalyzed intramolecular Giese-type radical cyclization and a diastereoselective, intramolecular enamine-mediated Michael addition with the latter annulation constructing the final D-ring to deliver rameswaralide. The discovery of a serendipitous oxidation state transposition of the tricyclic epoxy cycloheptenone proceeding through a presumed doubly vinylogous, E1-type elimination, enabled facile introduction of the required α-methylene butyrolactone. Preliminary biological tests of rameswaralide and precursors demonstrated weak cytotoxicity however the comparable cytotoxicity of a simple 6,7-bicyclic β-keto ester, corresponding to the CD-ring system of rameswaralide, to the natural product itself suggests that such bicyclic β-ketoesters may constitute an interesting pharmacophore that warrants further exploration.

Photochemical behaviors of pyruvic acid in multiple phases have been extensively studied, while those of its conjugate base, the pyruvate anion (CH

A genomic and spectroscopic signature-based search revealed a cycloaromatized enediyne, jejucarboside A (

Aspertaichunol A (b1/b), a polyketide with a novel scaffold, was isolated from the medicinal insect (iPeriplaneta americana/i)-derived endophyticiAspergillus taichungensis/iSMU01. Its structure was assigned on the basis of spectroscopic data and quantum chemical computational methods. Notably,b1/bpossesses an uncommon tricyclo[6.2.0.0sup2,6/sup]decane motif and an unusual bridgehead double bond (anti-Bredt system). A plausible biosynthetic pathway, involving a key intramolecular [2+2] cycloaddition and a reductive cyclization, is postulated. Finally, the immunomodulatory activity ofb1/bat 20 nM was evaluated by promoting Th9 cell differentiation from naive CD4sup+/supCD62Lsup+/supT cells.

A neighboring boronate group in the substrate provides a dramatic rate acceleration in transmetalation to copper and thereby enables organoboronic esters to participate in unprecedented site-selective cross-couplings. This cross-coupling operates under practical experimental conditions and allows for coupling between vicinal bis(boronic esters) and allyl, alkynyl, and propargyl electrophiles as well as a simple proton. Because the reactive substrates are vicinal bis(boronic esters), the cross-coupling described herein provides an expedient new method for the construction of boron-containing reaction products from alkenes. Mechanistic experiments suggest that chelated cyclic ate complexes may play a role in the transmetalation.

A Rh(III)-catalyzed weak enone carbonyl/ketone-assisted aerobic oxidative C-H olefination of aromatics with unactivated alkenes has been developed. This protocol involves cross-dehydrogenative Heck-type olefination reaction of various substituted biologically relevant chalcones and aromatic ketones such as acetophenones and chromones with various functionalized unactivated olefins in moderate to good yields. Further

An efficacious method for building fluorovinyl spiro-[imidazole-indene] and α-amino-β-naphthalenone skeletons synchronously has been shown to consist of Rh(III)-catalyzed C-H functionalization between 2

Computational programs accelerate the chemical discovery processes but often need proper 3-dimensional molecular information as part of the input. Getting optimal molecular structures is challenging because it requires enumerating and optimizing a huge space of stereoisomers and conformers. We developed the Python-based Auto3D package for generating the low-energy 3D structures using SMILES as the input. Auto3D is based on state-of-the-art algorithms and can automatize the isomer enumeration and duplicate filtering process, 3D building process, geometry optimization and ranking process. Tested on 50 molecules with multiple unspecified stereocenters, Auto3D is guaranteed to find the stereo-configuration that yields the lowest-energy conformer. With Auto3D we provide an extension of the ANI model. The new model, dubbed ANI-2xt, is trained on a tautomer-rich dataset. ANI-2xt is benchmarked with DFT methods on geometry optimization, electronic and Gibbs free energy calculations. Compared with ANI-2x, ANI-2xt provides a 42% error reduction for tautomeric reaction energy calculations when using the gold-standard coupled-cluster calculation as the reference. ANI-2xt can accurately predict the energies and is several orders of magnitude faster than DFT methods.

π-Molecules play important roles in many applications such as organic light-emitting devices, photocatalysis, photovoltaics, biosensors, and medicine. Very often, π-conjugated molecules with high utilization of excited states in the solid state are of great research interest. However, owing to the gap between molecular structure and effective molecular packing, there are very few designs toward π molecules with very high exciton utilization in the solid state. Herein, we report a new π skeleton, folded π, to achieve high exciton utilization in the solid state. Based on a "folded π" formula, 12 compounds with two or three folding π planes were designed and synthesized. We found that folded π molecules tend to form well-aligned 1D molecular columns of patterns ("box", "braid", or "stair") with high packing energy, which is mainly contributed by numerous weak π interactions. As a result of effective suppression of molecular motion, all the compounds show very high exciton utilization in solids.

A demethylative silyl radical cascade cyclization of 2-isocyanothioanisoles toward 2-silylated benzothiazole building blocks has been developed. The development of a "radical initiator-inhibitor symbiosis" system solves the challenge of otherwise dominant methyl radical-triggered side reactions brought about by kinetically unfavored generation of reactive silyl radical species. The products accessed in this protocol are amendable to various downstream functionalization reactions, including the quick construction of a topoisomerase II inhibitor via a Hiyama cross-coupling reaction and of an antiviral agent via a fluoride-/hydroxide-free nucleophilic substitution to acyl chloride.