Asymmetric Synthesis of Scillascillin-Type Homoisoflavonoid.

The first asymmetric synthesis of a scillascillin-type homoisoflavonoid was reported. Key reactions for the asymmetric synthesis of benzocyclobutene include catalytic reductive desymmetrization of malonic ester and an intramolecular C-H activation of the methyl group.

Synthetic study toward the diterpenoid aberrarone.

An approach to aberrarone, an antimalarial diterpenoid natural product with tetracyclic skeleton is reported. Key to the stereoselective preparation of the 6-5-5 tricyclic skeleton includes the mediation of Nagata reagent for constructing the C1 all-carbon quaternary centers and gold-catalyzed cyclopentenone synthesis through C-H insertion.

Total Synthesis of (±)-Codonopiloneolignanin A.

An intramolecular formal [3 + 2] cationic cycloaddition between benzylic carbocation and styrene was developed for the total synthesis of codonopiloneolignanin A. Further study shows benzocycloheptene as a good substrate for 1,3-dipolar cycloaddition, and a model study toward cephalocyclidine A skeleton was reported.

Recent advances on synthesis and biological activities of aurones.

Aurones are naturally occurring structural isomerides of flavones that have diverse bioactivities including antiviral, antibacterial, antifungal, anti-inflammatory, antitumor, antimalarial, antioxidant, neuropharmacological activities and so on. They constitute an important class of pharmacologically active scaffolds that exhibit multiple biological activities via diverse mechanisms. This review article provides an update on the recent advances (2013-2020.4) in the synthesis and biological activities of these derivatives. In the cases where sufficient information is available, some important structure-activity relationships (SAR) of their biological activities were presented, and on the strength of our expertise in medicinal chemistry and careful analysis of the recent literature, for the potential of aurones as medicinal drugs is proposed.

Design, synthesis and antifungal activity of amide and imine derivatives containing a kakuol moiety.

In continuation of our program to discover new potential antifungal agents, a series of amide and imine derivatives containing a kakuol moiety were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against four plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Compounds 7d, 7e, 7h, 7i and 7r showed obvious inhibitory activity against the corresponding tested fungi at 50 µg/mL. Especially, compounds 7e and 7r displayed more potent antifungal activity against B. cinerea than that of thiabendazole (a positive control). Moreover, compound 7e also exhibited good activity against A. alternata with EC50 values of 11.0 µg/mL, and the value was slightly superior to that of thiabendazole (EC50 = 14.9 µg/mL). SAR analysis showed that the ether group was a highly sensitive structural moiety to the activity and the type as well as position of substituents on benzene ring could make some effects on the activity.

Design, synthesis and biological evaluation of novel neuchromenin analogues as potential antifungal agents.

In continuation of our program to discover new potential antifungal agents, thirty-two neuchromenin analogues were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Compounds 6b-c, and 6l showed obvious inhibition activity on each of the fungi at 50 µg/mL. For the corresponding fungi, 7 of the compounds showed average inhibition rates of >80% at 50 µg/mL; especially, compounds 6b, 6d-e, and 6i-l displayed more potent antifungal activity against A. solani than that of thiabendazole (a positive control). Moreover, compound 6c also exhibited good activity against C. lunata with EC50 values of 12.7 µg/mL, and the value was much superior to that of thiabendazole (EC50 = 59.7 µg/mL). SAR analysis showed that the presence of conjugated structure, bearing a C=C bond conjugated to the C=O group, obviously decreased the activity; the type and position of the substituted R5 significantly influenced the activity. Furthermore, the significantly bioactive compounds 6b-e, 6g, 6i and 6l showed very low toxicities against HL-7702, BEL-7402 and HCT-8 cells. Resistance development assay indicated that compounds 6b-e and 6l failed to induce the two tested strains of fungi to develop resistance. SEM analysis initially revealed that compound 6d may exert its antifungal effect by damaging fungal cell wall.

Stereoselective Total Synthesis of (±)-5- epi-Cyanthiwigin I via an Intramolecular Pauson-Khand Reaction as the Key Step.

A convenient approach to the construction of the 5-6-7 tricarbocyclic fused core structure of cyanthiwigins via a Co-mediated Pauson-Khand reaction as a key step has been developed. The cyathane core intermediate obtained by this strategy was used in the concise synthesis of (±)-5- epi-cyanthiwigin I. The developed chemistry paves the way for the total synthesis of structurally diverse cyanthiwigins.

Furans as Versatile Synthons: Total Syntheses of Caribenol A and Caribenol B.

Two complex norditerpenoids, caribenols A and B, were accessed from a common building block. Our synthesis of caribenol A features the diastereoselective formation of the seven-membered ring through a Friedel-Crafts triflation and a late-stage oxidation of a furan ring. The first synthesis of caribenol B was achieved using an intramolecular organocatalytic α-arylation. An unusual intramolecular aldol addition was developed for the assembly of its cyclopentenone moiety, and the challenging trans-diol moiety was installed through a selective nucleophilic addition to a hydroxy 1,2-diketone. Our overall synthetic strategy, which also resulted in a second-generation synthesis of amphilectolide, confirms the usefulness of furans as powerful nucleophiles and versatile synthons.

Potent antimalarial 1,2,4-trioxanes through perhydrolysis of epoxides.

Perhydrolysis of a sterically congested multifunctional epoxide was achieved in ethereal H2O2 with the aid of a recently developed Mo catalyst. The resulting hydroperoxide cyclized to give a 1,2,4-trioxane, which could be readily elaborated into qinghaosu and a range of novel analogues. Some of the compounds with two such trioxane moieties showed in vitro antimalarial activity comparable to or even better than that of artesunate or chloroquine.

Simple analogues of qinghaosu (artemisinin).

A series of 1,2,4-trioxanes were synthesized in which the key peroxy bonds were installed through a molybdenum-catalyzed perhydrolysis of the epoxy rings. A core structure was identified that may serve as a promising lead structure for further investigations because of its high antimalarial activity (comparable to that of artesunate and chloroquine), apparent potential for scale-up and derivatization, and facile monitoring/tracing by using UV light.

A hydrogen peroxide based access to qinghaosu (artemisinin).

Attachment of H(2)O(2) onto the highly hindered quaternary C-12a in an advanced qinghaosu (artemisinin) precursor has been achieved through a facile perhydrolysis of a spiro epoxy ring with the aid of a previously unknown molybdenum species without involving any special equipment or complicated operations. The resultant ß-hydroxyhydroperoxide can be further elaborated into qinghaosu, illustrating an entry fundamentally different from the existing ones to this outstanding natural product of great importance in malaria chemotherapy.

Facile ring-opening of oxiranes by H(2)O(2) catalyzed by phosphomolybdic acid.

At ambient temperature, in the presence of catalytic amounts of phosphomolybdic acid (PMA), ethereal hydrogen peroxide reacted readily with a range of epoxides, giving corresponding beta-hydroxyhydroperoxides in high yields.

A broadly applicable mild method for the synthesis of gem-diperoxides from corresponding ketones or 1,3-dioxolanes.

Ketones or ketals were readily converted into the corresponding gem-dihydroperoxides in high yields by treatment with ethereal H(2)O(2) at ambient temperature in the presence of 2-5 mol % of phosphomolybdic acid.