Construction of oxygenated 2-azabicyclo[2.2.1]heptanes via palladium-catalyzed 1,2-aminoacyloxylation of cyclopentenes.

Herein, we describe a palladium-catalyzed 1,2-aminoacyloxylation of cyclopentenes to synthesize oxygenated 2-azabicyclo[2.2.1]heptanes. This reaction proceeds efficiently with a broad array of substrates. The products could be further functionalized to build up a library of bridged aza-bicyclic structures.

Stereoselective Synthesis of Monofluoroalkenylphosphine Oxides via Photoinduced Decarboxylative Coupling of α-Fluoroacrylic Acids with P(O)H Compounds.

Herein, a practical and efficient method for synthesizing monofluoroalkenyl phosphine oxides via photoinduced decarboxylative/dehydrogenative coupling of α-fluoroacrylic acids with phosphine oxides and phosphonates has been developed. Various α-fluoroacrylic acids and P(O)H compounds containing relevant functional groups, including tetrafluorobenzene and pentafluorobenzene, were converted into corresponding products with excellent E-stereoselectivity in satisfactory yields. This method can be extended to achieve the synthesis of monofluoroalkenyl silanes under similar conditions.

[Research progress on camptothecin and its derivative nano-prodrugs based on tumor microenvironment response].

Nano-prodrug, one of the most widely used nano-formulation at present, has excellent efficacies in tumor treatment with high potential and clinical value. Camptothecin and its derivatives have broad prospects in the preparation of prodrugs for the treatment of tumors. Given the special microenvironment of tumors, including partial acidity, high concentration of reactive oxygen species, high concentration of glutathione and enzyme concentration, a large number of tumor microenvironment-responsive camptothecin and its derivative prodrugs were prepared. This paper classified them from the microenvironment response types and drug release characteristics, reviewed the research progress of camptothecin and its derivative prodrugs based on safety and clinical trials, and analyzed the existing problems and deficiencies, hoping to provide references for the development of camptothecin and its derivatives.

Synthesis, biological evaluation and mechanism studies of C-3 substituted nitrogenous heterocyclic 23-Hydroxybetulinic acid derivatives as anticancer agents.

A series of novel nitrogenous heterocycle substituted 23-Hydroxybetulinic acid (23-HBA) derivatives with amide linkages at the C-3 position were designed, synthesized and evaluated for their antitumor activities. The biological screening results showed that most of the derivatives exhibited more potent antiproliferative activities than 23-HBA. In particular compound II-9 exhibited the most potent activities with IC50 values ranging from 1.96 µM to 6.20 µM against five cancer cell lines (B16, HepG2, A2780, MCF-7 and A549). The preliminary mechanism study showed that compound II-9 caused cell cycle arrest at G1 phase, induced cell apoptosis and depolarized mitochondria of B16 cells in a dose dependent manner. Moreover, western blot analysis indicated that compound II-9 down-regulated the expression of anti-apoptotic protein Bcl-2, up-regulated the expression of pro-apoptotic protein Bad, and activated cytochrome C and caspase 3 to cause cell apoptosis. In summary, II-9 may serve as a promising lead for the development of new natural product-based antitumor agents and deserve further investigation.

First total synthesis of hoshinoamide A.

Hoshinoamides A, B and C, linear lipopeptides, were isolated from the marine cyanobacterium Caldora penicillata, with potent antiplasmodial activity against chloroquine-sensitive Plasmodium falciparum. Herein, we describe the first total synthesis of hoshinoamide A by the combination of liquid-phase and solid-phase peptide synthesis. Liquid-phase synthesis is to improve the coupling yield of ʟ-Val3 and N-Me-ᴅ-Phe2. Connecting other amino acids efficiency and convergence is achieved by solid-state synthesis. Our synthetic strategy could synthesize the target peptide in high yield with good purity.

Development of a novel truncated deguelin derivative possessing nitric oxide donor as a potential anti-lung cancer agent.

Lung cancer is the leading cause of cancer death in the world. Natural product deguelin and its truncated analogs have been reported to be potential therapeutic agents for lung cancer. In order to improve the potency, a novel truncated deguelin derivative (4) possessing nitric oxide (NO) donor was designed and synthesized. The biological evaluation showed that hybrid 4 exerted potent activity with an IC50 value of 0.41 µM in H1299 cells. Mechanism studies showed that it arrested the cell cycle at G2/M phase and suppressed Hsp90 function. In addition, hybrid 4 demonstrated potent inhibitory activity on the migration and invasion of lung cancer cells. Together, the promising results warrant further development of hybrid 4 as a potential anticancer agent for the treatment of lung cancer.

Synthesis of gem-difluoroalkenes via nickel-catalyzed allylic defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides.

A nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides has been developed. Various substituted trifluoromethyl alkenes and epoxides were found to be suitable reaction substrates. This reaction enabled C(sp3)-C(sp3) bond construction through allylic defluorinative cross-coupling of trifluoromethyl alkenes under mild reaction conditions. This methodology was highly compatible with various sensitive functional groups, providing access to a diverse array of functionalized gem-difluoroalkene-containing alcohol compounds.

Base-free Ni-catalyzed Suzuki-type cross-coupling reactions of epoxides with boronic acids.

A Ni-catalyzed Suzuki-type cross-coupling of boronic acids with epoxides without an exogenous base and with broad substrate scope has been developed. The product selectivity of styrenyl epoxides is different from that of previous work. This methodology uses readily available starting materials to access a range of substituted alcohols, which are valuable feedstock chemicals.

Pd-Catalyzed decarboxylative cross-coupling reactions of epoxides with α,ß-unsaturated carboxylic acids.

A Pd-catalyzed decarboxylative cross-coupling of α,ß-unsaturated carboxylic acids with cyclic and acyclic epoxides has been developed. Both ß-monosubstituted and ß-disubstituted unsaturated carboxylic acids, as well as conjugated diene unsaturated carboxylic acids are suitable reaction substrates. Substituted homoallylic alcohols were obtained in moderate to good yields. The product was obtained as a mixture of diastereomers favoring the anti diastereomer of the cyclic epoxides. This work provides a method for the modification of complex organic molecules containing α,ß-unsaturated carboxylic acids.

Chemodivergent synthesis of N-(pyridin-2-yl)amides and 3-bromoimidazo[1,2-a]pyridines from α-bromoketones and 2-aminopyridines.

N-(Pyridin-2-yl)amides and 3-bromoimidazo[1,2-a]pyridines were synthesized respectively from α-bromoketones and 2-aminopyridine under different reaction conditions. N-(Pyridin-2-yl)amides were formed in toluene via C-C bond cleavage promoted by I2 and TBHP and the reaction conditions were mild and metal-free. Whereas 3-bromoimidazopyridines were obtained in ethyl acetate via one-pot tandem cyclization/bromination when only TBHP was added, the cyclization to form imidazopyridines was promoted by the further bromination, no base was needed, and the versatile 3-bromoimidazopyridines could be further transferred to other skeletons.

Trisubstituted olefin synthesis via Ni-catalyzed hydroalkylation of internal alkynes with non-activated alkyl halides.

The stereoselective synthesis of tri-substituted alkenes is challenging. Herein, we report a Ni-catalyzed regio- and stereo-selective hydroalkylation of internal alkynes with non-activated alkyl halides. This method does not use any sensitive organometallic reagents and shows good functional group compatibility, which enables the efficient synthesis of many tri-substituted olefins from readily available coupling partners. It also provides a straightforward method for the modification of bioactive organic molecules.

Palladium-catalyzed oxidative cross-coupling of azole-4-carboxylates with indoles: an approach to the synthesis of pimprinine.

An efficient and straightforward method for the production of 5-(3-indolyl)azoles incorporating the privileged structures indoles and azoles via palladium-catalyzed double C-H bond cleavage under mild conditions was disclosed. As expected, this protocol provided an easy method for the synthesis of indole alkaloids pimprinine and WS-30581 A in moderate yields.

Solvent-controlled switchable C-H alkenylation of 4-aryl-1H-pyrrole-3-carboxylates: application to the total synthesis of (±)-rhazinilam.

A solvent-controlled switchable C-H alkenylation of 4-aryl-1H-pyrrole-3-carboxylates via a Pd(OAc)2 catalyzed oxidative Heck reaction was first realized. The corresponding C2 and C5 alkenylation products were obtained in good yields with high regioselectivities, respectively. The selective C5-alkenylation was successfully applied to the total synthesis of (±)-rhazinilam.

Advances in chemical synthesis of structurally modified bioactive RNAs.

Methods for the chemical synthesis of RNA have been available for almost half century, and presently, RNA could be chemically synthesized by automated synthesizers, using protected ribonucleosides preactivated as phosphoramidites, which has already been covered by many reviews. In addition to advancement on synthetic methods, a variety of modifications have also been made on the synthesized oligonucleotides, and previous reviews on the general synthesis of RNAs have not covered this area. In this tutorial review, three types of modifications have been summarized standing at the viewpoint of medicinal chemistry: (1) modifications on nucleobase, comprising substituent introduction and replacement with pseudobase; (2) modifications on ribose, consisting of modifications on the 2', 3' or 5'-position, alternation of configuration, and conformational restriction on ribose; (3) modifications on internucleoside linkages, including amide, formacetal, sulfide, sulfone, ether, phosphorothiolate and phosphorothioate linkages. Synthetic methods achieving these modifications along with the functions or values of these modifications have also been discussed and commented on.