Hypercohones A-C,acylphloroglucinol derivatives with homo-adamantane cores from Hypericum cohaerens

Three new homo-adamantanyl type natural products were derived from polyprenylated polycyclic acylphloroglucinol.Hypercohones A-C(1-3),along with five other known hypercohones(4-8),were isolated from the aerial parts of Hypericum cohaerens.The structures of 1-3 were elucidated on the basis of comprehensive spectroscopic analysis.The inhibitory activities of these isolates against five human cancer cell lines in vitro were tested.

Lycopodine-Type Alkaloids from Lycopodium japonicum

Three new lycopodine-type alkaloids,4a-hydroxyanhydrolycodoline(1),4a,6a-dihydroxyanhydrolycodoline(2),and 6-epi-8b-acetoxylycoclavine(3),and an artifact,lycoposerramine G nitrate(4),along with seventeen related known compounds,were isolated from the club moss Lycopodium japonicum Thunb.ex Murray(Lycopodiaceae).Their structures were elucidated by extensive spectroscopic methods as well as X-ray analysis.Compounds 1–4 were evaluated for their acetylcholine esterase inhibitory activity.

Chemical constituents from the aerial parts of Musella lasiocarpa

Phytochemical investigation of the aerial parts of the monotypic plant,Musella lasiocarpa,led to the isolation of four rare bicyclic diarylheptanoids,musellarins B-E(2-5),two new phenylphenalenones,2-methoxy-9-(3′,4′-dihydroxyphenyl)-1H-phenalen-1-one(9),2-methoxy-9-(3′-methoxy-4′-hydroxyphenyl)-1H-phenalen-1-one(10),a new acenaphtylene derivative,trans-(1S,2S)-3-(4′-methoxyphenyl)-acenaphthene-1,2-diol(13),and two new sucrose esters,1,2′,3′,4′,6′-O-pentaacetyl-3-O-trans-p-coumaroylsucrose(16),1,2′,3′,4′,6′-O-pentaacetyl-3-O-cis-p-coumaroylsucrose(17),together with nine known compounds.In addition,(4E,6E)-1-(3′,4′-dihydroxyphenyl)-7-(4′′-hydroxyphenyl)-hepta-4,6-dien-3-one(15)was isolated for the first time from a natural source.The structures of new compounds were elucidated by analysis of their spectroscopic data.Compounds 2,6,8-10,12,and 14 were cytotoxic toward several of the human tumor cell lines(HL-60,SMMC-7721,A-549,MCF-7,and SW480).Of these,the new compound 9 was the most potent one,with IC50 values of 5.8,10.3,6.3,3.3,and 2.3μM,respectively.

Lycodine-Type Lycopodium Alkaloids from the Whole Plants of Huperzia serrata

t Three new lycodine-type Lycopodium alkaloids,namely 1-methyllycodine(1),8a-hydroxy-15,16-dehydro-desN-methyl-a-obscurine(2),N-methyl-16-hydroxyhuperzine B(3),and one new natural lycodine-type Lycopodium alkaloid,N-methylhuperzine A(4),along with 11 known analogues(5–15),were isolated from the whole plants of club moss Huperzia serrata.The structures of 1–4 were elucidated on the basis of NMR spectroscopic and mass spectrometry data.Among them,compound 1 was the first lycodine-type alkaloid possessing a methyl group at C-1.In addition,the structure of 5 was confirmed by the single-crystal X-ray crystallography data and its^(13)C NMR was reported for the first time in current study.Compounds 1–5 were tested their BACE1 inhibitory activity.

Carinatines A and B,Lycopodium Alkaloids from Phlegmariurus carinatus

Carinatine A(1),a C16N2-type Lycopodium alkaloid possessing a 5/6/6/6 ring system formed by a new C-4/C-12 bond,and carinatine B(2),the first derivative of lycojaponicumin C,along 16 known compounds,were isolated from the whole plant of Phlegmariurus carinatus.Their structures were elucidated based on the spectroscopic data.The two new isolates were no inhibitory activity for the acetylcholinesterase(AChE).

New Lycopodium alkaloids from Lycopodium obscurum

Three new Lycopodium alkaloids,obscurumines C-E(1-3),along with nine known compounds,were isolated from the club moss Lycopodium obscurum L.Structures of the new compounds were determined on the basis of their spectroscopic analysis and the relative configurations of 1 were established by X-ray crystallographic analysis.All the new isolates were tested for the acetylcholinesterase(AChE)inhibitory activity.

neo-Clerodane diterpenoids from Salvia dugesii and their bioactive studies

Salvia dugesii is an invasive plant in Yunnan,China.To tentatively explore its utilization,a systematic phytochemical investigation was carried out on this plant,which led to the isolation of five new neo-clerodane diterpenoids,dugesins C-G(1-5),together with six known ones.Their structures were determined by comprehensive NMR and MS spectroscopic analysis.It was noteworthy that the eleven isolates,composed of five different carbocyclic systems derived from the neo-clerodane diterpenoid skeleton,were reported from the same plant for the first time.The anti-feedantial,cytotoxic,and antiviral activities of the isolates were evaluated.Dugesin F(4)was tested to be a non-toxic antiviral compound against influenza virus FM1.

(±)-Evodiakine,A Pair of Rearranged Rutaecarpine-Type Alkaloids From Evodia rutaecarpa

(±)-Evodiakine(1a and 1b),a pair of rearranged rutaecarpine-type alkaloids with an unprecedented 6/5/5/7/6 ring system,were isolated from the nearly ripe fruits of Evodia rutaecarpa.Separation of the enantiomers have been achieved by chiral HPLC column.The structures of(±)-evodiakine were unambiguously elucidated by 1D and 2D NMR spectra,mass spectrometry,and single-crystal X-ray diffraction.Their absolute configurations were determined by comparison of experimental and calculated electronic circular dichroism spectra.A hypothetical biogenetic pathway for(±)-evodiakine was also proposed.Compounds 1a,1b,and the racemate(1)were tested for their cytotoxic and anti-inflammatory activities.

Isolation,Structural Assignment of Isoselagintamarlin A from Selaginella tamariscina and Its Biomimetic Synthesis

Isoselagintamarlin A(1),a selaginellin analogue featured a rare benzofuran unit,was isolated from Selaginella tamariscina.Its complete structural assignment was established through a combination of high-feld NMR technique and biomimetic synthesis.Notably,isoselagintamarlin A(1)was successfully synthesized via sequential oxidations and intramolecular cyclization.

Lycoplanines B-D,Three Lycopodium Alkaloids from Lycopodium complanatum

A novel Ci7N Lycopodium alkaloid(LA),lycoplanine B(1),containing an unusual formyl group,along with two new LAs,lycoplanines C(2)and D(3),were isolated from the whole plant of Lycopodium complanatum.Their structures were elucidated by extensive NMR techniques,including 1D-and 2D-NMR experiments,as well as comparing their spectral data with those of the known analogues.A possible biogenetic pathway for 1 was also proposed.

Exploring of drug leads from diversity-oriented Michael-acceptor library derived from natural products

A potential strategy for drug lead identification and in-active natural products re-discovery is elaborated.Starting from fifteen structurally diverse natural products,a focused library featured by Michael acceptors is constructed with IBX mediated oxidation.Biological assay on five tumor cell lines indicates that four Michael acceptors,8a,11a,12a,14a,are with improved cytotoxicity(3-10 folds more potent than the parent compounds),which merit further investigations.Further thiol-sensitive assay of the active hit 8a revealed that it was an irreversible Michael acceptor.The results suggest that the strategy is not only effective and relatively high discovery rate(28%),but also resource saving.

Euglobal-IIIa, a novel acylphloroglucinol-sesquiterpene derivative from Eucalyptus robusta: absolute structure and cytotoxicity

Euglobal-IIIa (1), a novel acylphloroglucinol-sesquiterpene derivative, and a known analogue, have been isolated from leaves of Eucalyptus robusta. The structures was elucidated by extensive spectroscopic data and by comparison with data reported in literature, while the absolute configuration of 1 was determined by the X-ray diffraction analysis. Compound 1 exhibited comparable cytotoxicity with that of cisplatin against five human cancer cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480 with IC50 values of 15.7, 15.5, 17.6, 14.3, and 21.8 μM, respectively.

Lyconadins G and H,Two Rare Lyconadin-Type Lycopodium Alkaloids from Lycopodium complanatum

Two rare lyconadin-type Lycopodium alkaloids,lyconadins G(1)and H(2),together with four known ones(3–6),were isolated from Lycopodium complanatum.The structures were determined on the basis of their spectroscopic analyses,and the absolute configuration of 1 was established by an X-ray crystallographic analysis.It is the first time to establish the absolute configuration of lyconadin-type Lycopodium alkaloid by an X-ray diffraction experiment.In addition,these findings may provide more information for the biosynthesis of lyconadins.

Four new labdane-type diterpenoid glycosides from Diplopterygium laevissimum

Four new labdane-type diterpenoid glycosides,laevissiosides A-D(1-4)were isolated from the 95%ethanol extract of Diplopterygium laevissimum(Christ)Nakai,along with two known analogues,18-b-D-glucopyranosyl ester-sclareol(5)and 18-hydroxy-sclareol(6).The structures of compounds 1-4 were elucidated by extensive 1D and 2D NMR spectroscopy as well as high-resolution MS analyses.All isolated compounds were evaluated for their cytotoxic effects.

Development and structure-activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors

11β-Hydroxysteroid dehydrogenase 1(11β-HSD1)represents a promising drug target for metabolic syndrome,includ-ing obesity and type 2 diabetes.Our initial screen of a collection of natural products from Danshen led to the identi-fication of tanshinones as the potent and selective 11β-HSD1 inhibitors.To improve the druggability and explore the structure-activity relationships(SARs),more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials.More than 10 derivatives exhibited potent in vitro 11β-HSD1 inhibitory activity and good selectivity over 11β-HSD2 across human and mouse species.Based on the biological results,SARs were further discussed,which was also partially rationalized by a molecular docking model of 1 bound to the 11β-HSD1.Remarkably,compounds 1,17 and 30 significantly inhibited 11β-HSD1 in 3T3-L1 adipocyte and in livers of ob/ob mice,which merits further investigations as anti-diabetic agents.This study not only provides a series of novel selective 11β-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes,but also expands the boundaries of the chemical and biological spaces of tanshinones.

Synthesis of L-Ascorbic Acid Lactone Derivatives

A small focused library which comprised of L-AA lactone derivatives was built with a facile method.This reported method was optimized by modifying the acidity of the solvent.As a result,12 L-AA lactones were synthesized.Among these lactones,lactones 8–12 were new compounds.The cytotoxicity of these synthetic compounds were investigated.