Search

Bioassay-directed fractionation of a n-hexane extract of Couepia polyandra using an assay to detect inhibitors of the lyase activity of DNA polymerase β resulted in the isolation of the new triterpene 3β,16β,23-triacetoxyolean-12-en-28-oic acid (1) and four known compounds, oleanolic acid, betulinic acid, stigmasterol, and β-sitosterol. The structure of the new compound was established on the basis of extensive 1D and 2D NMR spectroscopic interpretation. All five compounds inhibited DNA polymerase β lyase activity.

Bioassay-guided fractionation of a CH2Cl2/MeOH extract of the wood of Vepris punctata resulted in the isolation of three new furoquinoline alkaloids, 5-methoxymaculine (1), 5,8-dimethoxymaculine (2), and 4,5,6,7,8-pentamethoxyfuroquinoline (3), in addition to the four known alkaloids flindersiamine (4), kokusaginine (5), maculine (6), and skimmianine (7). The structures of the new alkaloids 1−3 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All the isolated compounds were tested against the A2780 human ovarian cancer cell line, and all seven alkaloids showed weak cytotoxic activity.

Bioassay-guided fractionation of a CH2Cl2/MeOH extract of the small twigs of Brachylaena ramiflora var. ramiflora resulted in the isolation of the two new triterpene esters 1 and 2 and five known triterpenoids, α-amyrin palmitate (3), β-amyrin palmitate (4), β-amyrin acetate (5), lupeyl acetate (6), and lupeol (7). The structures of the two new compounds were established as kairatenyl palmitate (1) and hopenyl palmitate (2) on the basis of 1D and 2D NMR spectroscopic data interpretation and chemical conversions. All the isolated compounds showed weak cytotoxicity against the A2780 human ovarian cancer cell line.

Bioassay-guided fractionation of the plant Acacia aulacocarpa, guided by a bioassay for Tie2 tyrosine kinase activity, yielded the novel triterpene 3,21-dioxo-olean-18-en-oic acid (1) as the first naturally occurring non-protein inhibitor of Tie2 kinase. The structure of 1 was assigned by analysis of spectral data. In addition to its activity as an inhibitor of Tie2 kinase, compound 1 also shows modest activity against a variety of cultured mammalian cells.

The structure of apakaochtodene A, the minor isomer of two tetrahalogenated ochtodene monoterpenes, isolated from the red marine alga Portieria hornemannii (Lyngbye) Silva has been identified as 6(S*)-bromo-1,4(S*),8(R*)-trichloro-2(Z)-ochtodene (1) by NMR spectral and X-ray crystallographic analysis. Its geometrical isomer, apakaochtodene B (2), which could not be separated from 1 and thus characterized as a 95:5 mixture of 2:1 had ¹H and ¹³C NMR spectral characteristics similar to previously known ochtodene (3) and the related tetrahalogenated monoterpene 4.

Bioassay-directed fractionation of the MeOH extract of Solanum umbelliferum afforded solasodine (1), O-acetylsolasodine (2), and solasodine 3-O-β-d-glucopyranoside (3). Alkaloids 1 and 2 exhibited significant activity toward DNA repair-deficient yeast mutants, whereas 3 and the synthetic analogues N-acetylsolasodine (4) and N,O-diacetylsolasodine (5) were found to be inactive. Compounds 2 and 3 are new natural products.

In a continuation of our search for potential tumor inhibitors from plants, it was found that the CH2Cl2−MeOH (1:1) extracts from Digitalis purpurea and Penstemon linarioides both showed PKCα-inhibitory bioactivity. Bioassay-directed fractionation of the extract from D. purpurea yielded the new, weakly active phenylethanoid glycoside 2-(3-hydroxy-4-methoxy-phenyl)-ethyl-O-(α-l-rhamnosyl)-(1→3)-O-(α-l-rhamnosyl)-(1→6)-4-O-E-feruloyl-β-d-glucopyranoside (1) together with the four known compounds calceolarioside A (2), calceolarioside B (3), forsythiaside (4), and plantainoside D (5). The extract from P. linarioides yielded the three known glycosides leucosceptoside A (6), acteoside (7), and poliumoside (8), together with the iridoid plantarenaloside (9). All of the isolated compounds, except compound 9, showed inhibitory activity against PKCα with IC50 values (in μM) of 125 (1), 0.6 (2), 4.6 (3), 1.9 (4), 14.8 (5), 19.0 (6), 9.3 (7), and 24.4 (8).

Bioassay-guided fractionation of the CH2Cl2−MeOH extract of Pinus flexilis using an assay for protein kinase C (PKC) inhibitory activity led to the isolation of the two new bioactive diarylheptanoids (3R)-1,7-bis(3,4-dihydroxyphenyl)-3-(β-d-glucopyranosyl)heptan-3-ol (1) and its aglycon (3R)-1,7-bis(3,4-dihydroxyphenyl)heptan-3-ol (2), together with the three known bioactive compounds, hirsutenone (3), oregonin (4), and hirsutanonol (5). The IC50 values of compounds 1−5 in the PKC assay were 1.4, 1.6, 1.4, 8.6, and 4.6 μg/mL, respectively.

Fractionation of the MeCOEt extract of Mimulus clevelandii yielded the novel 4-geranyl-5-hydroxy-2(3H)-benzofuranone (1) and the five known 6-geranylflavanones diplacone (2a), 3‘-O-methyldiplacone (2b), diplacol (2c), mimulone (2d), and 3‘-O-methyldiplacol (2e). 2D-NMR methods required revision of assignments for diplacone and diplacol and resolved the uncertainty in the site of methylation for the methyl ethers.

Continuation of a previous study on Renealmia alpinia resulted in the isolation of the new labdane diterpenoid 3, together with two known diterpenoids. The structure of the new diterpenoid was determined by a combination of NMR techniques and HRFABMS.

Treatment of a mixture of paclitaxel and cephalomannine with bromine under mild conditions yields a readily separable mixture of paclitaxel and 2‘‘,3‘‘-dibromocephalomannine. Cephalomannine can be regenerated by treating 2‘‘,3‘‘-dibromocephalomannine with zinc in acetic acid.