Proposal for structure revision of pinofuranoxin A through total syntheses of stereoisomers.

The relative configuration of the epoxide functionality in pinofuranoxin A (1), α-alkylidene-ß-hydroxy-γ-methyl-γ-butyrolactone with trans-epoxy side chain isolated by Evidente et al. in 2021, was revised by DFT-based spectral reinvestigations and stereo-controlled synthesis. The present investigation demonstrates the difficulty of the configurational elucidation of the stereogenic centers on the conformationally flexible acyclic side-chains. Sharpless's enantioselective epoxidations and dihydroxylations were quite effective in the reinvestigations of the configurations. As our syntheses made all diastereomers available, these would be quite effective in the next structure-biological activity relationship studies.

Structure-Activity Relationship of Anti-malarial Allylpyrocatechol Isolated from Piper betle.

Malaria disease remains a serious worldwide health problem. In South-East Asia, one of the malaria infection "hot-spots," medicinal plants such as Piper betle have traditionally been used for the treatment of malaria, and allylpyrocatechol (1), a constituent of P. betle, has been shown to exhibit anti-malarial activities. In this study, we verified that 1 showed in vivo anti-malarial activity through not only intraperitoneal (i.p.) but also peroral (p.o.) administration. Additionally, some analogs of 1 were synthesized and the structure-activity relationship was analyzed to disclose the crucial sub-structures for the potent activity.

Toosendanin relatives, trypanocidal principles from Meliae Cortex.

Africa Trypanosomiasis remains a serious health problem, but the approved drugs for this disease are so few that novel trypanocidal compounds are demanded. In search for trypanocidal principles from medicinal plants, we found MeOH extracts of Meliae Cortex with potent activity through the screening from about 300 kinds of methanolic extract. By bioassay-guided fractionation from this extract through the liquid-liquid partition and subsequent chromatographic technique using silica gel and ODS, finally we disclosed toosendanin (1) and its relatives as active principles. These active congeners showed not only potent trypanocidal activity but also little cytotoxicity to display the excellent selective index. Taking the isolated amount as well as trypanocidal activity into consideration, 1 was disclosed to be the responsible active principle in Meliae Cortex. Additionally, the derivatives of 1 were chemically prepared from 1 and bioactivity of them were also evaluated. Through the comparison with their trypanocidal activity among the isolated relatives and the synthesized derivatives of 1, the epoxide moiety was revealed to be essential for their potent trypanocidal activity. Furthermore, 3-O-acetyl group and 7-hydroxyl group were presumed to be important functional groups and introduction of methylpropionyl group into hemiacetal hydroxy moiety was clarified to enhance their typanocidal activity.

Oenothein B, dimeric hydrolysable tannin inhibiting HCV invasion from Oenothera erythrosepala.

The envelope proteins of the hepatitis C virus (HCV), E1 and E2, have been revealed to be essential for invasion of HCV. Thus, we were engaged in the search for the inhibitors against HCV invasion through the assay system using the model virus expressing recombinant HCV envelopes, E1 and E2. Now, we disclosed dimeric hydrolysable tannin oenothein B (1) from MeOH extract of Oenothera erythrosepala as an active principle for inhibition of HCV invasion and its potency was almost the same as that of monomeric hydrolysable tannin, tellimagrandin I (2). Furthermore, by use of stereoselectively prepared 1-ß- and 1-α-O-methyl tellimagrandin Is (4 and 5), the introduction of methyl moiety into 1-hydroxy group of 2 was clarified to result in slightly reduction of activity and ß-isomer was revealed to exhibit a little stronger activity than α-one.

Inhibitor for FcεRI expression on mast cell from Verbasucum thapsus L.

We found out 2',3'-dihydroxypuberulin from South American medicinal plant, V. thapsus L., as a candidate of an anti-allergic lead which inhibits the expression of high-affinity receptor of IgE (FcεRI) on the surface of mast cells. Furthermore, the analysis of structure-activity relationship by using synthesized 2',3'-dihydroxypuberulin analogs revealed that both hydroxy groups in the side chain and both of methyl moieties on phenolic hydroxy groups were crucial for potent activity, but absolute configuration of C-3' position wasn't. The active principle, 2',3'-dihydroxypuberulin, was disclosed to down-regulate the mRNA level of ß-chain of FcεRI, different from previous reported active natural product reducing γ-chain level.