Development of a novel phosphoramidite-selenide ligand for Pd-catalyzed asymmetric allylic substitution.

A novel chiral P,Se-heterodonor ligand has been designed and prepared through an efficient and simple operation. This ligand can be successfully applied to Pd-catalyzed asymmetric allylic substitution with C- and N-nucleophiles, producing a diverse range of chiral allylic products in high yields and enantioselectivities (up to 99% yield and 95% ee).

Neo-clerodane Diterpenoids with Hypoglycemic Effects in Vivo from the Aerial Parts of Salvia hispanica L.

A new neo-clerodane diterpenoid, salvihispin H (1), and six known ones (2-7) were identified from the aerial parts of Salvia hispanica L. The structure and absolute configuration of 1 were elucidated by extensive analysis of spectroscopic (1 H, 13 C, and 2D NMR, and HR-ESI-MS) and single-crystal X-ray diffraction data. The anti-diabetic effects of salvihispin H (1) and salvifaricin (2) were evaluated in diabetic db/db mice. The data showed that 1 and 2 could significantly reduce fasting blood glucose level and improve insulin resistance, and compound 1 exerted glucose-lowering effect more quickly than metformin. In addition, 1 and 2 could also reduce serum TG level in db/db mice. These results demonstrated that compounds 1 and 2 could be considered as potent candidates for the therapy of type 2 diabetes mellitus (T2DM).

Huperserratines A and B, Two Macrocyclic Lycopodium Alkaloids with an Unusual Skeleton from Huperzia serrata.

Huperserratines A (1) and B (2), two Lycopodium alkaloids with an unprecedented 5-aza-bicyclo[10.4.0]hexadecane skeleton and an oxime function, were isolated from Huperzia serrata. Their structures including absolute configurations were determined by extensive NMR spectroscopic and X-ray diffraction analysis. Compounds 1 and 2 were the first examples of macrocyclic Lycopodium alkaloids with an aza-12-membered ring. A plausible biogenetic pathway of these compounds was also proposed. Compound 1 exhibited moderate anti-HIV-1 activity with an EC50 of 52.91 µg/mL and a therapy index greater than 3.78.

Three new Lycopodium alkaloids from Lycopodium japonicum.

Three new Lycopodium alkaloids (1-3), together with 15 known alkaloids, were isolated from club moss Lycopodium japonicum. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR spectra. Compound 1 has an unusual ß-oriented methyl group substituted at C-15 and an α-hydroxy cyclopentenone moiety. All new alkaloids were evaluated for the inhibition of T-type calcium channel.

Guaiane-Type Sesquiterpenoids from Alismatis Rhizoma and Their Anti-inflammatory Activity.

Twelve guaiane-type sesquiterpenoids, including four new ones, 10-O-methyl-orientalol A (1), 10-O-ethyl-alismoxide (2), 3ß,4ß-expoxy-chrysothol (3), orientalol G (4), and a new norsesquiterpenoid, orientalol H (5), were isolated from Chinese Alismatis Rhizoma, the dried rhizome of Alisma orientale. The structures of new compounds were elucidated on the basis of spectroscopic data. Moreover, the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells of all compounds was tested.

Protostane-Type Triterpenoids from Alisma orientale.

Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16ß-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.

Sesquiterpenoids from the twigs and leaves of Fokienia hodginsii.

A rare carotane-type sesquiterpenoid, forkienin A (1), a new eudesmane-type sesquiterpenoid, forkienin B (2), and a new natural eudesmane-type sesquiterpenoid, forkienin C (3), were isolated from the twigs and leaves of Fokienia hodginsii, along with eight known sesquiterpenoids. The structures of the new compounds were elucidated on the basis of their spectroscopic analysis, including 1D and 2D NMR methods. All compounds were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines.

Lignan Glucosides from the Stem Barks of Illicium difengpi.

In this study, four new lignan glucosides, named difengpiosides A-D (1-4), were isolated from the stem barks of Illicium difengpi, together with seven known compounds 5-11. Their structures were identified on the basis of spectroscopic analyses (1D and 2D NMR, HRESIMS, CD) and a comparison with literature data. All the compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.

Hupehenols A-E, selective 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors from Viburnum hupehense.

Five selective 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) competitive inhibitors, hupehenols A-E (1-5), were isolated from Viburnum hupehense. The structure elucidation indicated that compounds 1-5 are new 20,21,22,23,24,25,26,27-octanordammarane triterpenoids. Their structures were established on the basis of NMR spectroscopic and mass spectrometric analysis. Hupehenols A-E (1-5) showed inhibition against human 11ß-HSD1, with hupehenols B (2) and E (5) having IC50 values of 15.3 and 34.0 nM, respectively. Moreover, hupehenols C (3) and D (4) are highly selective inhibitors of human 11ß-HSD1 when compared to murine 11ß-HSD1.

Three new iridoids from two Viburnum species.

Three new iridoids, 10-deacetyl suspensolide A aglycone (1), 7-deacetyl suspensolide A aglycone (2), and 7,10-dideacetyl suspensolide A aglycone (3), were isolated from two species of Viburnum. Their structures were elucidated on the basis of spectroscopic methods, including 1D and 2D NMR techniques. Compound 2 exhibited moderate anti-inflammatory activity against NO production in LPS-stimulated RAW 264.7 cells with IC50 of 17.2 µM.

Four new fawcettimine-related alkaloids from Phlegmariurus squarrosus.

Four new fawcettimine-related alkaloids (1-4), together with 17 known ones, were isolated from club moss Phlegmariurus squarrosus. Notably, compound 1 was the derivative of lycoflexine with an unprecedented additional methyl group at C-17. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-MS, as well as by comparison with the literature data. All new compounds were tested for their ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) inhibitory activities.

Sesquiterpenoids from Tussilago farfara and their inhibitory effects on nitric oxide production.

Tussilagone (TSL) and its allied sesquiterpenoids were considered as the main active principles of the flower buds of Tussilago farfara, which has been widely used in China as an antitussive herbal medicine. Six new bisabolane-type sesquiterpenoids, tussfararins A-F (1-6), along with 12 known sesquiterpenoids, were isolated from the flower buds of T. farfara. Structures of the new compounds were elucidated by extensive spectroscopic analysis. The biological analysis showed that compounds 1, 3, 6, and 7 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with IC50 values of 13.6-24.4 µM.

New Lycopodium alkaloids from Phlegmariurus squarrosus.

Four new Lycopodium alkaloids (1-4), together with 15 known ones, were isolated from club moss Phlegmariurus squarrosus. Notably, 8α-hydroxylycojapodine A (1) was the first derivative of lycojapodine A (5) which was a novel C16N-type Lycopodium alkaloid with an unprecedented 6/6/6/7 tetracyclic ring system. Their structures were elucidated based on the spectroscopic data, including 1D and 2D NMR techniques.

Diterpenoids from the twigs and leaves of Fokienia hodginsii.

Five new isopimarane diterpenoids, fokihodgins A-E (1-5), four new labdane diterpenoids, fokihodgins F-I (6-9), and one new icetexane diterpenoid, fokihodgin J (10), as well as 18 known diterpenoids were isolated from Fokienia hodginsii. The structures of the new compounds were determined on the basis of their spectroscopic analysis, and the absolute configurations of 1 and 6 were established by X-ray crystallographic analysis. Compound 9 showed moderate cytotoxicity against HL-60 and SMMC-7721 cell lines, with IC50 values of 9.10 and 7.50 µM, respectively.

Further lignans from Saururus chinensis.

Three new sauchinone analogues, sauchinones B-D (1-3), together with sauchinone (4), were isolated from the aerial part of Saururus chinensis. Structures of the new compounds were determined by extensive spectroscopic data as well as X-ray analysis. Compounds 3 and 4 inhibited nitric oxide production in lipopolysaccharide stimulated RAW 264.7 cells with IC50 values of 13.0 and 14.2 µM, respectively.

Triterpenoids and steroids with cytotoxic activity from Emmenopterys henryi.

Two new ursane-type triterpenoids, 3ß,19α,23-trihydroxyurs-12-en-24-al-28-oic acid (1) and 3ß,19α,24-trihydroxy-23-norurs-12-en-28-oic acid (2), two new pregnane derivatives, 3ß,12ß-dihydroxy-5α-pregnane-14,16-dien-20-one (9) and 12ß-hydroxy-5α-pregnane-14,16-dien-3,20-dione (10), and eight known compounds were isolated from the twigs and leaves of Emmenopterys henryi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 4, 11, and 12 showed cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines with IC50 values in the range of 3.11-20.12 µM.

Discovery and Biomimetic Semisynthesis of Spirophyllines A-D from Uncaria rhynchophylla.

Spirophyllines A-D (1-4), four new spirooxindole alkaloids all characterized by the spiro[pyrrolidin-3,3'-oxindole] core and a rare isoxazolidine ring, were isolated from Uncaria rhynchophylla. Their structures were determined by spectroscopic methods and confirmed by X-ray crystallography. Based on the biomimetic semisynthesis strategy, compounds 1-8 were synthesized in three steps via the key reactions of 1,3-dipolar cycloaddition and Krapcho decarboxylation from corynoxeine. Interestingly, compound 3 showed moderate inhibitory activity against the Kv1.5 potassium channel (IC50 = 9.1 µM).

Polycyclic polyprenylated acylphloroglucinols and cytotoxic constituents of Hypericum androsaemum.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), androforin A and hyperandrone A, together with twelve known compounds, were isolated from the aerial parts of Hypericum androsaemum. Their structures were established by detailed spectral analysis. In the cytotoxic assay, 1,4-O-diferuloylsecoisolariciresinol showed activities comparable with those of cisplatin, and acetyloleanolic acid exhibited moderate inhibitory effects against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cancer cell lines.

Eleven undescribed alkaloids from the rhizomes of Sinomenium acutum and their IDO1 and TDO inhibitory activities.

Eleven previously undescribed alkaloids, named sinometumines A-K, along with three known alkaloids, were isolated from the rhizomes of Sinomenium acutum. The chemical structures of these unreported compounds were established using extensive spectroscopic methods (IR, UV, HRESIMS, and NMR), and their absolute configurations were determined by single crystal X-ray diffraction analyses and calculated electronic circular dichroism spectroscopy (ECD). Sinometumine D was the first aporphine-type derived alkaloid inner salt with a rearranged dibenzofuran ring backbone. Sinometumine E was a rare protoberberine-type alkaloid with a complex 6/6/6/6/6/6 hexacyclic skeleton. This was the first report of alkaloids with these two skeletons isolated from S. acutum. All isolates were evaluated for their inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). Lysicamine possessed noteworthy inhibitory activities as an IDO1/TDO dual inhibitor with IC50 values of 6.22 ± 0.26 µM and 23.76 ± 2.93 µM, respectively, and liriodenine revealed moderate dual inhibition with IC50 values of 31.65 ± 4.44 µM and 15.64 ± 0.26 µM. The intermolecular interactions and binding modes between lysicamine and IDO1/TDO were elaborated by molecular docking studies.

Cassane diterpenoids from the seeds of Caesalpinia bonduc and their nitric oxide production and α-glucosidase inhibitory activities.

Ten previously undescribed cassane diterpenoids, cassabonducins A-J, and eleven known compounds were isolated from the seeds of Caesalpinia bonduc. The structures of the undescribed compounds were elucidated by extensive analysis of spectroscopic data (IR, HRESIMS, and 1H, 13C and 2D NMR) and their absolute configurations were determined by the ECD data and single-crystal X-ray diffraction analysis. ε-Caesalpin-Ⅶ was obtained from natural resources for the first time. Cassabonducin A possessed noteworthy inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 value of 6.12 µM. Cassabonducin D and neocaesalpin N showed moderate α-glucosidase inhibition at the concentration of 50 µM with inhibitory capacities of 47.17% and 43.83%, respectively.