Hai-Yan Wu

New Bicyclo[3.1.0]hexane Unit ent-Kaurane Diterpene and Its seco-Derivative from Isodon eriocalyx var. laxiflora

Neolaxiflorin A (1), an unprecedented ent-kaurane diterpenoid with a bicyclo[3.1.0]hexane unit, and its seco-derivative, neolaxiflorin B (2), along with two known compounds 3 and 4 were isolated from the leaves of Isodon eriocalyx var. laxiflora. The absolute configuration of 1 was determined by spectral methods and single crystal X-ray diffraction analysis. Compound 4 and the synthesized compound 5 exhibited significant cytotoxicity.

Bioactive Enmein-Type ent-Kaurane Diterpenoids from Isodon phyllostachys

Thirty-two enmein-type ent-kaurane diterpenoids, including 13 new compounds, were isolated from the aerial parts of Isodon phyllostachys. Compounds 1 and 2 are the first examples of 3,20:6,20-diepoxyenmein-type ent-kauranoids, and the structures of these new compounds were established mainly by analyzing NMR and HREIMS data. The absolute configurations of 1 and 8 and the relative configuration of 9 were determined using single-crystal X-ray diffraction. Compounds 11, 15, 20, and 21 were active against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), with IC50 values ranging from 1.2 to 5.0 μM. Compounds 3, 11, 15, 17, 20, 21, 25, and 29 strongly inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values ranging from 0.74 to 4.93 μM.

Cytotoxic ent-Kaurane Diterpenoids from Isodon wikstroemioides

Phytochemical investigation of EtOAc extracts of the aerial parts of Isodon wikstroemioides afforded 18 new ent-kaurane diterpenoids (wikstroemioidins E-V, 1-18), along with 17 known analogues (19-35). The absolute configurations of 1 and 16 were confirmed by single-crystal X-ray diffraction analysis. The isolates were screened against five human tumor cell lines; compounds 3, 4, 9, 11-13, 23, 25-28, and 33 exhibited significant cytotoxic activity against all five, with IC50 values ranging from 0.4 to 5.1 μM. In addition, 17 of the isolates strongly inhibited nitric oxide production in LPS-activated RAW264.7 macrophages.

Enmein-type 6,7-seco-ent-Kauranoids from Isodon sculponeatus

Fourteen enmein-type 6,7-seco-ent-kaurane diterpenoids, seven new ones (sculponins M-S, 1-7) and seven known compounds (8-14), were isolated from the aerial parts of Isodon sculponeatus . Compound 1 is the first example of an ent-kauranoid, possessing a 11,12-epoxy group, and compounds 6 and 7 have a rare 3,6-epoxy group. The structures were established primarily by NMR and MS methods, and the absolute configurations of 1, 3, and 6 were determined by single-crystal X-ray diffraction. Compound 14 showed significant cytotoxic activity against five human tumor lines, with IC50 values ranging from 1.0 to 3.5 μM, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC50 value of 2.2 μM.

Laxiflorolides A and B, epimeric bishomoditerpene lactones from Isodon eriocalyx.

Laxiflorolides A (1) and B (2), two unprecedented epimeric bishomoditerpene lactones with a unique C(22) framework, along with laxiflorins P-R (3-5), maoecrystal P (6), maoecrystal C (7), and eriocalyxin B (8), were isolated from the leaves of I. eriocalyx var. laxiflora. The structures of 1 and 2, including the absolute configurations, were determined by spectroscopic methods and single-crystal X-ray diffraction analysis. All of the compounds isolated were evaluated for their cytotoxicity against five tumor cell lines. Compounds 3, 6, and 8 showed remarkable cytotoxic activity against certain cell lines compared with the positive control.

Diterpenoids from Isodon sculponeatus

Phytochemical investigation of the aerial parts of Isodon sculponeatus afforded six new 7,20-epoxy-ent-kauranoids, sculponins U-Z (1-6), and 11 known diterpenoids (7-17). The structures of these new compounds were elucidated primarily by means of extensive spectroscopic analysis, and the absolute configuration of 1 was determined by single crystal X-ray diffraction. Compound 5 exhibited weak cytotoxic activity against HL-60, SMMC-7721, MCF-7, and SW-480 cell lines, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 value of 13.8 μM.

Four new diterpenoids from Isodon eriocalyx var. laxiflora

Four new diterpenoids, laxiflorins S-V (1–4), bearing four different types, and one known compound, laxiflorin O (5), were isolated from Isodon eriocalyx var. laxiflora. Compound 1 was the first example of ent-kauranoids bearing a unique C24 carbon framework and compound 4 was the first example of 3,4-seco-ent-abietane diterpenoids from the Isodon genus. Their structures were determined by spectroscopic methods (UV, IR, MS, NMR).

Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon wikstroemioides.

Seven new ent-kaurane diterpenoids, isowikstroemins A-G (1-7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1-4 exhibited significant activity with IC50 values ranging from 0.9 to 7.0 μM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages.

Laxiflorol A, the first example of 7,8:15,16-di-seco-15-nor-21-homo-ent-kauranoid from Isodon eriocalyx var. laxiflora

Laxiflorol A (1), an unprecedented 7,8:15,16-di-seco-15-nor-21-homo-ent-kauranoid, and its precursor analogue, laxiflorol B (2), were isolated from the leaves of Isodon eriocalyx var. laxiflora. The absolute configuration of 1 was determined by spectral methods and quantum chemical calculations. Compound 2 exhibited weak cytotoxicity.

Ent-kaurane and ent-abietane diterpenoids from Isodon phyllostachys

Four new diterpenoids, phyllostachysins I–L (1–4), along with a known one, hebeiabinin B (5), were isolated from the aerial parts of Isodon phyllostachys (I. phyllostachys). Compounds 1 and 2 feature an ent-kaurane backbone, and 3, 4 and 5 bear an ent-abietane skeleton. Their structures were elucidated by means of spectroscopic analysis. Compounds 3 and 4 exhibited significant cytotoxic activity against human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and strongly inhibited NO production in LPS-stimulated RAW264.7 cells.