Manganese-catalyzed intermolecular oxidative annulation of alkynes with γ-vinyl aldehydes involving acylation and alkylation is described, thus providing a scenario for the divergent synthesis of bridged carbocyclic systems. By means of this manganese-catalyzed alkyne dicarbofunctionalization strategy, three chemical bonds, including two C–C bonds and one C–H bond, are formed via an aldehyde C(sp2)–H oxidative functionalization/[4 + 2] annulation/protonation cascade.

Two series of 12 novel thioxoflavones Mannich base derivatives 5a–f and 6a–f were synthesized via Mannich reaction of 4′,7-dimethoxy-5-hydroxyflavothione (3) or 3′,4′,7-trimethoxy-5-hydroxyflavothione (4) with appropriate aliphatic amines or alicyclic amines and formaldehyde. Thioxoflavones 3 and 4 were prepared from 4′,7-dimethoxy-5-hydroxyflavone (1) and 3′,4′,7-trimethoxy-5-hydroxyflavone (2) with Lawesson's reagent, respectively. Their antiproliferative activities in vitro were evaluated on a panel of three human cell lines (HeLa, HCC1954, and SK-OV-3) by CCK-8 assay. The results showed that most of the thioxoflavones and their Mannich base derivatives exhibited potential antiproliferative activities on the tested cancer cell lines, with IC50 values ranging from 9.16 to 55.50 μM. In particular, thioxoflavone 4 and the thioxoflavone Mannich base derivatives 5a and 5d showed the best antiproliferative activity on all three human cancer cell lines; they are promising candidates worthy of further development. The structures of all synthesized compounds were confirmed by 1H NMR, 13C NMR, IR, and MS techniques.

A series of polymethoxyflavonoids (3–16) were synthesized through dehydrogenation, O-methylation, glycoside hydrolysis, bromination, microwave-assisted aromatic nucleophilic substitution, dimethyldioxirane oxidation and regioselective demethylation, starting from abundant and inexpensive natural sources naringin and hesperidin. All the synthetic compounds were test for antiproliferative activities on human cervical carcinoma Hela cell line by the standard CCK-8 assay, the result showed that most of the target compounds exhibited moderate to potent antiproliferative activities on Hela cells comparable with the positive control cis-Platin. Among them, 5-hydroxypolymethoxy flavonoid 13 showed the strongest activity (IC50 0.791 μM).Open image in new window

Two novel series of sixteen aminoalkyl-substituted polymethoxychalcone derivatives 2a―2h and 3a―3h were synthesized from 2′-hydroxy-3,4,5,4′,6′-pentamethoxy chalcone(1) through extending alkoxy side chain at the 2′-position, and introducing amine hydrogen bond receptor at the end of the side chain. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR and MS techniques. Furthermore, all the compounds were tested for antiproliferative activities in vitro against a panel of three human cell lines(HeLa, HCC1954 and SK-OV-3) via CCK-8 assay. The results show that all the target compounds exhibit antiproliferative activities against the three human cancer cells with IC50 values of 4.62―48.21 μmol/L, except compound 2h against SK-OV-3 cells. Most of these compounds were more active when compared to the positive control cis-Platin.

A series of novel coumarin glycoside esters(1—9) was synthesized through the acylation reaction of 4-methylcoumarin-7-O-β-D-glucoside(11) with different long chain fatty acids catalyzed by lipase in organic medium. The acylation occurred regioselectively at the 6′-OH of glycosyl moiety. The enzymatic synthesis was optimized to achieve 54%—70% yield using immobilized lipase(Novozym 435, 10 mg/mL) as catalyst and acetone and pyridine( 9:1, volume ratio, water content<1%) as solvent with an acyl donor/coumarin glycoside molar ratio of 10:1 at a temperature of 40—50 °C for 96 h. All the synthesized compounds were confirmed.

Fourteen novel pterostilbene (1) and \(3^\prime \)-methoxy pterostilbene (2) Mannich base derivatives (3–16) were synthesized via the microwave-assisted Mannich reaction of 1 or 2 with various secondary amines and formaldehyde. The regioselectivity of the reaction occurred preferentially at \(\hbox {C-3}^\prime (\hbox {and /or C-5}^\prime )\) position of the B-ring of stilbene. The biological testing results showed that all the target compounds exhibit antiproliferative activity against Hela cells from \(\hbox {IC}_{50}=22.5\)–\(65.3\,\upmu \hbox {M}\). Compounds 1–3, 7, 11–13, and 16 displayed higher (lower \(\hbox {IC}_{50}\) values) activity than the positive control cisplatin \((\hbox {IC}_{50}= 41.3\,\upmu \hbox {M})\).

Four coumarin glycosides(1–4) and four coumarin triazoylglycosides(5–8) were synthesized by phase transfer catalytic glycosylation and copper-catalyzed azide-alkyne cycloaddition(CuAAC) respectively from 4-methyl-7-hydroxyl coumarin(4-methylumbelliferone). The structures were characterized by 1H NMR, MS or IR. The fluorescent properties of the coumarin glycosides and triazoylglycosides were studied in different solvents and compared to those of 4-methyl-7-hydroxyl coumarin.

Two natural dihydrobenzofuran neolignans licarin A(1) and dihydrocarinatin(2) were systhesized from isoeugenol with Ag2O-catalyzed biomimetic oxidative coupling as the key step. Four novel dihydrobenzofuran triazolylglycoside(3–6) were achieved in good yields via Cu(I)-catalyzed azide-alkyne cycloadditions of licarin A terminal alkynes with different azide acetylated sugar and deacetylation with sodium methoxide in anhydrous methanol. The structures of all the compounds synthesized were determined by elemental analysis, MS, 1H NMR and 13C NMR. And the inhibition activity of synthesized compounds on α-glucosidase was determined by in vitro experiments. The results show that triazolyglycosides 3, 4, 5 and 6 show moderate inhibitory activity on α-glucosidase.

Apigenin-7-O-β-d-glycosides 1–8 and acacetin-7-O-β-d-glycosides 9–16 were semisynthesized from 4′-O-benzyl apigenin 17 and acacetin 18 by glycosidation and deprotection with the corresponding α-acetylglycosyl bromide, respectively. Compounds 17 and 18 were prepared by iodination followed by base-induced elimination, 4′-O-benzylation, or 4′-O-methylation and acid hydrolysis using naringin as starting material which is readily available and cheap. Their cytotoxic potential against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) was evaluated by standard MTT method. The results show that compounds 2, 9, and 19 exhibit moderate cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480, while compound 3 exhibits potent cytotoxicity against MCF-7 selectively. Among the synthesized target compounds, 3, 4, 7, 11, 12, 15, and 16 were new compounds, the natural product 8 was the first synthesized and the synthesis of natural products 5, 6, 13, and 14 was efficiently improved by the new synthetic routes.Apigenin-7-O-β-d-glycosides 1–8 and acacetin-7-O-β-d-glycosides 9–16 were semisynthesized and their cytotoxic activities were evaluated.