Normal-phase and reversed-phase silica gel column chromatography and semi-preparative high performance liquid chromatography were applied to study the chemical constituents of the stems and twigs of the Hainan mangrove plant, Excoecaria agallocha L. A new 3,4-seco-ent-kaurane diterpenoid, named agallochanin acid A (1), and a rare ent-tetranorlabdane diterpenoid, named agallochanin acid B (2), along with four known diterpenoids were isolated. Their structures including absolute configurations were characterized via HR-ESI-MS, extensive 1D and 2D NMR investigations and calculated and experimental electronic circular dichroism (ECD) data. All isolates were tested for their inhibitory effects on NO production in lipopolysaccharide (LPS)-activated BV-2 cells. ent-3,4-Seco-17-oxo-kaur-4(19),15(16)-dien-3-oic acid (3) and ent-15-hydroxy- labda-8(17),13E-dien-3-one (5) exhibited considerable anti-neuroinflammatory activities with IC₅₀ values of (14.32±1.99) and (4.24±0.37) μmol/L.

The propargylation of various nucleophiles including indoles, phenol, anisole, enoxysilanes, and alcohols was rapidly achieved using catalytic copper(II) triflate. The reaction conditions are mild, allowing for quick reactions in an undried solvent and under atmospheric air. The desired products are obtained with good yields.

In order to obtain antibacterial candidate compounds, using the principle of pharmacodynamic fragment combination, the thiazole fragment was introduced into the structure of the seedling compound osthole. Twenty-six osthole derivatives were designed and synthesized, and confirmed by ¹H NMR, ¹³C NMR and elemental analysis. The antibacterial activities against S. aureus, E. coli, methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FREC) were evaluated. The results showed that the minimum inhibitory concentrations (MICs) of N-(4-(2-fluorophenyl)thiazol-2-yl)-2-((8-(3-methyl- but-2-en-1-yl)-2-oxo-2H-chromen-7-yl)oxy)acetamide (5g) were 2, 4, 2, 4 μg/mL, respectively. The MICs of N-(4-cyclo- propylthiazol-2-yl)-2-((8-(3-methylbut-2-en-1-yl)-2-oxo-2H-chromen-7-yl)oxy)acetamide (5w) were 2, 2, 4, 4 μg/mL, respectively. The MICs of N-([2,4'-bithiazol]-2'-yl)-2-((8-(3-methylbut-2-en-1-yl)-2-oxo-2H-chromen-7-yl)oxy)acetamide (5x) were 1, 2, 2, 2 μg/mL. respectively. Their anti-S. aureu activities were comparable to the control drug oxacillin and superior to norfloxacin, and anti-E. coli, MRSA, and FREC were superior to the control drugs oxacillin and norfloxacin. The connection of thiazole fragment to the structure of osthole can effectively enhance antibacterial activities.

A more feasibly convergent synthesis of selective estrogen receptor degrading agent (S)-8-(4-((1-(3-fluoropropyl)- pyrrolidin-3-yl)oxy)phenyl)-7-(4-hydroxyphenyl)-5,6-dihydronaphthalen-2-ol was reported, featured with concise work up and absence of regioselectivity dilemma.

A Pd(OAc)₂-catalyzed efficient synthesis of 2-(1-isochromen-3-yl)acetaldehyde derivatives was achieved by the carboxyl-directed C—H bond alkylation/annulation of aryl acids with vinyl ethylene carbonate. This method has the advan- tages of ready availability of starting materials and operational simplicity, providing an alternative access to isochroman-1-one derivatives.

One new germacrane-type sesquiterpene lactone, named as salviatanolide A (1) was isolated from an ethanol extract of the whole plant of Salvia castanea. Its structure was elucidated by 1D and 2D-NMR and HRESIMS spectra, and its absolute configuration was determined by single crystal X-ray crystallography. The anti-Alzheimer’s disease (AD) activity of 1 was evaluated using humanized Caenorhabditis elegans AD pathological model. Compound 1 significantly delayed AD-like symptoms of worm paralysis phenotype, which may be potential to be served as anti-AD agent candidate.

In order to find pesticide lead compounds with high fungicidal activity, a series of unreported allyl benzoate compounds containing triazole were designed and synthesized. The structures were confirmed by ¹H NMR and HRMS, and the crystal structure of (R,S)-(Z)-1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl)allyl 2,3-dichlorobenzoate (5j) was determined by X-ray single crystal diffraction. The bioassay results showed that (R,S)-(Z)-1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl)allyl benzoate (5a), (R,S)-(Z)-1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl)allyl 2-fluorobenzoate (5g) and (R,S)-(Z)-1,3-diphenyl-2-(1H-1,2,4-triazol-1- yl)allyl 3-methylbenzoate (5n) exhibited good control efficacy against Sclerotinia sclerotiorummore than 70% at 50 mg/L.

A novel visible-light-introduced reaction for the construction of quinazolinone derivatives via radical cyclization of 2-aminobenzamides with benzyl alochols under water phase has been developed. The reaction has been achieved in high yield under mild conditions by using I₂ as photocatalyst, which is cheap, available and easy to handle. A variety of quinazolinones were obtained in yields up to 92%. It might provide a promising protocol for the synthesis of quinazolinone derivatives. Its application was performed by the synthesis of N-(2-fluoro-5-methylphenyl)-6-(2,2,2-trifluoroethoxy)pteridin-4-amine, which displayed significant inhibitory activity.

Thirteen novel pyridyl oxazoamide compounds were synthesized using pyridine-2-formaldehyde as the starting material through cyclization, oxidation, substitution, hydrolysis, chlorination and ammonolysis reactions via the disclosed intermediate derivatization method (IDM). The structures of title compounds were characterized by ¹H NMR and HRMS. Preliminary bioassay results indicated that at 100 mg/L, 7 compounds exhibited 100% fungicidal activities against Botrytis cinerea, and N-(4-fluorophenyl)-2-(pyridin-2-yl)oxazole-4-carboxamide (7b) exhibited 100% fungicidal activities against Rhizoctonia solani. Further fungicidal activity test results suggested that some of the target compounds had better fungicidal activity than azoxystrobin, which was worthy of further study.

A palladium-catalyzed migratory diarylation of unconjugated cyclohexadiene is disclosed, which exihibits high 1,3-regioselectivity and exclusive cis-diastereoselectivity. The excellent selectivity suggests that the olefin does not dissocate from the palladium during chain-walking. This study provides a simple method for the synthesis of 1,3-diaryl-substituted cyclohexanes

The enantioselective syntheses of (-)-indolizidine 167B and (+)-coniine were described based on the asymmetric hydrogenation of racemic δ-hydroxy esters via kinetic resolution. With optically active chiral δ-hydroxy ester (S)-4 and chiral 1,5-diol (R)-5 obtained by asymmetric hydrogenation of racemic ethyl 5-hydroxyoctanoate (rac-4) with chiral spiro iridium catalyst Ir-(R)-SpiroPAP as chiral starting materials, the efficient enantioselective syntheses of (-)-indolizidine 167B and (+)-coniine were achieved by using intramolecular reductive amination and N-substitution/cyclization, respectively, as a key step to construct the chiral aza-bicyclic[4.3.0]nonane skeleton and chiral piperidine ring. This provides new efficient methods for enantioselective syntheses of indolizidine and piperidine alkaloids.

A new method for the synthesis of 8-hydroxyisocoumarin is reported. 8-Hydroxyisocoumarin was synthesized from Meldrum's acid by Friedel-Crafts acylation, carbonyl protection, ester reduction and deprotection. The key intermediate 3-ethynyl-2-(hydroxymethyl)cyclohex-2-en-1-one was synthesized by acidic cycloaddition, aromatization of cyclohexanone ring and 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) oxidation. The structures were characterized by ¹H NMR, ¹³C NMR, IR, and HRMS.

A series of 3-arylisoxazoline-pyrazole-5-carboxamide derivatives derived from ethyl 5,5-dimethoxy-2,4-dioxopentanoate were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR and HRMS. The preliminary bioassay indicated that most title compounds exhibited positive potency against Mythimna separate (Walker) at 500 mg/L. At the concentration of 100 mg/L, three compounds were still moderately active against Mythimna separate (Walker) (lethal rate≈60%). At 500 mg/L, four compounds were also active against Aphis craccivora. The results indicated that the potential of these 3-arylisoxazoline-pyrazole-5-carboxamide derivatives can be utilized in insecticide research with further optimization.

Three kinds of C(3)-1,2,4-triazolyl-1,5-benzothiazepines, 2,3-dihydro/2,5-dihydro/2,3,4,5-tetrahydro-3-(1,2,4-tria-zolyl)-4-aryl-1,5-benzothiazepines, were designed and synthesized. The synthesis conditions of intermediates and target products were studied, and the structures of two by-products were determined. The antimicrobial activity test of the target products showed that 2,3-dihydro/2,5-dihydro-3-(1,2,4-triazolyl)-4-aryl-1,5-benzothiazepines exhibited high inhibitory effects on C. neoformans and C. albicans. At concentration of 200 μg/disc, the inhibitory effects of four compounds on C. neoformans were stronger than that of fluconazol, and the inhibitory effects of three compounds on C. albicans were stronger than that of fluconazol. The preliminary study on the structure-activity relationship of antifungal revealed that 1,2,4-triazolyl and C=N double bond were the key function groups in the antifungal activity of 2,3-dihydro-3-(1,2,4-triazolyl)-4-aryl-1,5-benzothiazepines.

A concise synthesis of 3-dehydroxyphomonol has been accomplished in six steps from commercially available (R)-4-chloro-3-hydroxy-butyric acid ethyl ester or (S)-2-propyl-oxirane. The key steps involved Grignard reaction, Prins cyclization and palladium-catalyzed intramolecular alkoxycarbonylation to install the tetrahydropyran ring. The synthesis demonstrated an application of protecting-group-free strategy.

Puquitinib mesylate is a novel phosphatidylinositol 3-kinases (PI3K) inhibitor, which has been shown to be effective in the treatment of cancer. A convenient protocol for the synthesis of the compound at kilogram scale is described, using 2,6-dichloropurine as starting material through amino-protection, S_N2 reaction with high regioselectivity, Buchwald-Hartwig coupling reaction, amino-deprotection and salt-forming reaction. The process is easy to operate and provides an effective way at kilogram scale produce with 48% yield in total.

In the presence of triphenylarsine and catalytic amount of Rh₂(OAc)₄, one pot reactions with carbonyl compounds and dimethyl diazomalonate give the corresponding alkylidene and arylidene malonates in moderate to excellent yields (59%~99%). The scope of the carbonyl compounds covered a broad range, including aromatic and aliphatic aldehydes and ketone. The reaction was easily scaled up to gram scale with 0.5 mol% rhodium catalyst loading. The preliminary mechanistic studies showed that the olefination proceeded via a rhodium-carbene transformed arsonium ylide pathway.

Five clerodane diterpenes were isolated from the roots of Polyalthia laui during a systematic phytochemical investigation. Their structures were elucidated by the NMR and HRMS data as methyl (4→2)-abeo-2,13-diformyl-cleroda-2,12E-dien-15-ate (1), (E)-ent-cleroda-3,12-diene-15,16-dioic acid (2), 14,15-dinorclerod-3-ene-2,13-dione (3), solidagolactone (4), and 16-hydroxy-3,13Z-kolavadien-16,15-olide (5). Among them, compounds 1~2 are new clerodane diterpenes. Biological evaluation of compounds 1~5 against human Hela, A549, MCF-7 and HL-60 human cancer cell lines showed that all com-pounds displayed moderate cytotoxicities against various human cancer cell lines with IC₅₀ ranged from 13.22 to 37.16 μmol/L.

A series of novel pyridine derivatives containing oxime esters have been synthesized from 3-methylpyridine, ethyl pivalate, hydroxylamine hydrochloride and substituted benzoic acid by addition, oximization and esterification reactions,which has the advantages of moderate reaction condition and high yield. Their structures were elucidated by IR, ¹H NMR, ¹³C NMR and elemental analysis. Moreover, the target compounds were evaluated for their antifungal activity against two plant pathogens by the mycelium growth rate method. The results indicated that O-(4-bromobenzoyl)-3,3-dimethyl-1-(pyridin-3-yl)butan-2-one oxime (3h) and O-(4-chlorobenzoyl)-3,3-dimethyl-1-(pyridin-3-yl)butan-2-one oxime (3j) exhibited strong antifungal activity against S. sclerotiorum with EC₅₀ values of 5.07 and 4.81 μg/mL, and 3h, 3j and O-(3,4-dichlorobenzoyl)-3,3-dimethyl-1-(pyridin-3-yl)butan-2-one oxime (3l) displayed high antifungal activity against B. cinerea with EC₅₀ values of 4.98, 5.44 and 6.34 μg/mL, respectively.

Through a variety of chromatographic techniques and spectroscopic methods, sixteen diterpenes were isolated and identified from the ethanol extraction of the roots of Salvia kiaometiensis Lévl. Their structures were identified to be 6,8,11,13-abietatetraen-12-ol dimer (1), kiaometin (2), miltirone (3), tanshinone ⅡA (4), crypotanshione (5), tanshindiol C (6), ferruginol (7), 2-isopropyl-8-methylphenanthrene-3,4-dione (8), tanshinone I (9), trijuganone B (10), dihydrotanshinone I (11), grandifolias C (12), przewalskin (13), tanshinlactone (14), 6,7,8,9-tetrahydro-1,6,6-trimethylfuro[3,2-c]naphtha[2,1-e]oxepine-10,12-dione (15), and salmilalbanone (16). Compound 1 is a new abietane diterpenes dimer, and compound 2 is a new 7,8:7,20-diepoxy-nor-abietane diterpenes. All of the diterpenes were isolated from this plant for the first time.

Chiral spirooxindole γ-lactones with three stereogenic centres are rare. An efficient asymmetric construction of novel spiro-fused 2-oxindole/α-methy-paraconnic ester is reported, which was offered via organocatalytic Michael reaction of propaldehyde and olefinic oxindoles, with subsequent H₂O₂/K₂CO₃ system-mediated α-hydroxylation/hemiacetalization cascade reaction under oil/water two-phase conditions, and final oxidative γ-lactonization by pyridinium chlorochromate (PCC). The presented strategy features mild reaction conditions, excellent yields (91%~98%) and enatioselectiveties (87%~95%), and accordingly constitutes a facile and new method for the synthesis of chiral multisubstituted spirooxindole γ-lactones. All structures of new products were confirmed by ¹H NMR, ¹³C NMR and HRMS techniques.

Totally 21 compounds were isolated from the EtOAc extract of fermentation broth of fungus Xylaria polymorpha (Pers.: Fr.) Grer, including two new drimane-type sesquiterpenoids named polymorphines A and B (1~2) and one new phenyloxolane compound named 2-methyl-2-(4-hydroxymethylphenyl) oxolane (3), together with 18 known compounds 4~21. The structures of these compounds were elucidated by NMR and single-crystal X-ray diffraction analysis. Compound 2 exhibited anti-acetylcholinesterase and α-glucosidase inhibitory activities. Moreover, compound 3 showed moderate inhibitory activitiy against the nematode Panagrellus redivivus with mortality ratio of 59.6% at 2.5 mg/mL.

In order to find new cyanoacrylate lead compounds, a series of novel cyanoacrylates containing substituted pyridyl moiety were prepared by the method of active substructure combination. The structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR and elemental analyses. Preliminary bioassay data displayed that in postemergence treatment 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino(2-methoxy)ethyl ester (7l) had 95% herbicidal activity against Brassica juncea at 1500 g/ha and 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino-[2-(2,4-difluorophenoxy)]ethyl ester (7e), 7l and 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino-(2-ethoxy)ethyl ester (7m) showed 80%, 80% and 100% herbicidal activity against Stellaria media, respectively. Additionally, 2-cyano-3-methylthio-3-[4-(5-trifluoromethylpyridyl-2-amino)]benzylamino[2-(2-fluorophenoxy)]ethyl ester (7b), 7l and 7m all exhibited 100% herbicidal activity against Chenopodium serotinum L. at 1500 g/ha.

The berberine chloride was synthesized starting from benzo[d][1,3]dioxole with the mild condition and the simple operation in overall 33% yield. The route includes the five steps of nucleophilic ring opening, deprotection and cyclization and so on. All intermediates were determined by ¹H NMR, ¹³C NMR and MS techniques.