C_(30)-C_(32) LANOSTANES——A NOVEL SERIES OF TETRACYCLIC TRITERPENOID HYDROCARBONS IDENTIFIED IN CHINESE TERTIARY LACUSTRINE SEDIMENTS

A series of novel tetracyclic triterpanes based on the lanostane skeleton, ranging in cars-bon number from C30 to C32, were identified for the first time in Eocene lacustrine depo-its of Biyang Depression, China. These compounds have been identified by GC, GC- MS, andcoinjection with authentic standard, as 8β（H）, 9α（H）- lanostane (C30), 24-methyl- lanostane(C31) and 24- ethyl- lanostane (C32). Mechanisms are proposed for the origin and geologicalfate of these compounds. To the best of our knowledge, this is the first confirmed occur-rence of lanostanes in the sedimentary record.

IDENTIFICATION OF LANOSTANES AND THEIR POSSIBLY GEOCHEMICAL SIGNIFICANCE IN BIYANG DEPRESSION

In the study, a series of C30-C32 lanostane homologs have been identified from Eogene source rocks and crude oils of Biyang depression in Henan Province, China. Based upon the geochemical investigations and simulating experiments, the idea that the generation of lanostane may mainly be related to the specific original organic inputs and low maturity has been proposed.

Four 14(13→12)‑Abeolanostane Triterpenoids with 6/6/5/6‑Fused Ring System from the Roots of Kadsura coccinea

Four new rearranged 6/6/5/6-fused lanostane-type triterpenoids,kadcoccitanes A-D(1-4),were isolated from the roots of Kadsura coccinea,and their structures were mainly elucidated by comprehensive analysis of their spectroscopic data.Additionally,the structure of 1 was ambiguously verifed by single-crystal X-ray difraction,while the structure of 2,which features a novel 8,16-epoxy motif,was validated by quantum chemical calculation of NMR parameters and ECD spectrum.Moreover,1 and 4 were found to exhibited anticoagulant activity,while 3 and 4 were found to possess anti-platelet aggregation activity.

Intestinal Absorption of Ergostane and Lanostane Triterpenoids from Antrodia cinnamomea Using Caco-2 Cell Monolayer Model

Antrodia cinnamomea is a precious medicinal mushroom.It exhibits promising therapeutic effects on cancer,intoxication,hypertension,hepatitis,and inflammation.Its major bioactive constituents are ergostane and lanostane triterpenoids.In this study,we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A.cinnamomea.The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method.In the case of pure compounds,ergostanes 5(25R-antcin H),6(25Santcin H)and 10(25R-antcin B)could readily pass through the Caco-2 cell layer,whereas lanostanes 13(dehydroeburicoic acid)and 14(eburicoic acid)could hardly pass through.When the cells were treated with A.cinnamomea extract,antcins A,B,C,H and K(1–6 and 9–11)were absorbed via passive transcellular diffusion,and showed high PAB and PBA values(>2.5×10^(-5) cm/s).Meanwhile,the lanostanes dehydrosulphurenic acid(8),15a-acetyldehydrosulphurenic acid(12),13 and 14 exhibited poor permeability.Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats.This study could also be helpful in predicting the intestinal absorption of A.cinnamomea in human.

Lanostane-Type Triterpenoids from Scilla scilloides and Structure Revision of Drimiopsin D

Two hitherto unknown lanostane-type triterpenoids,namely scillascillol(1)and scillascillone(2),and a hitherto unknown norlanostane-triterpene glycoside,namely scillascilloside B-1(3),were isolated from the ethanol extract of the whole plants of Scilla scilloides.Their structures were elucidated on the basis of extensive spectroscopic studies.In addition,the structure of drimiopsin D(6a)has been revised as 2,5-dimethoxy-8-methyl-1,3,6-trihydroxyxanthone(6)by reanalysis of the spectroscopic data.

Two new lanostane triterpenoids from Abies sachalinensis

The continuous chemical investigation on the ethyl acetate （EtOAc） soluble fraction of the MeOH extract afforded two new lanostane triterpenoid derivatives including one with a rearranged lanostane skeleton. They were identified as 3,4-seco-8-（14→13R）abeo-17,13-friedo-9β-lanosta-4（28）, 7,14（30）,24-tetraen-26,23-olide-23-hydroxy-3-oic acid （1） and 7,14-mariesa- dien-3oL-hydroxy-25-methoxy-26-oic acid （2）. Structural determination of these compounds were carried out by the spectral studies especially by the two digital （2D）-NMR and high-resolution MS experiences.

Triterpenoids and phenolics from the fruiting bodies of Inonotus hispidus and their activations of melanogenesis and tyrosinase

Two new 24-methyl lanostane triterpenoids,hispindic acids A and B（1 and 2）,and a new phenolic compound,hispinine（7）,along with nine known compounds（3-6,and 8-12）,were isolated from the fruiting bodies of Inonotus hispidus.Their structures were elucidated based on the extensive analysis of spectroscopic data（NMR and HRMS）.Hispindic acid A（1） possesses an unusual formyl group at C-30.Compounds 1,3-4,and 8 showed stronger activate abilities of melanogenesis and tyrosinase in B16 melanoma cells than those of positive control,8-methoxypsoralen,at 50 μmol/L

Applanoids A—E as the First Examples of C-15/C-20 Michael Adducts in Ganoderma Triterpenoids and Their PXR Agonistic Activity

Ganoderma triterpenoids(GTs),a class of major active constituents of Ganoderma fungi,possess diverse structures and remarkable activities.In the present study,nine new GTs,namely applanoids A—I(1—9),were isolated from the medicinal fungus of Ganoderma applanatum.Their structures including absolute configurations were established by comprehensive spectroscopic analyses and ECD calculation.Applanoids A—E(1—5)represent the first example of GTs with 6/6/5/6/5 pentacyclic system and the formation of the ether ring between C-15 and C-20 involves Michael addition reaction.Furthermore,compounds 1—8 were evaluated for their human pregnane X receptor(hPXR)agonistic activity using dual-luciferase reporter gene assay,and the results showed that compounds 1,2 and 4 can dose-dependently activate hPXR.This investigation further illustrated the structural diversity of GTs and provided new insights for searching PXR agonists from GTs.

Lanostane Tetracyclic Triterpenoids as Important Sources for Anti-Inflammatory Drug Discovery

Inflammation is a defensive reaction of the human body to numerous detrimental stimuli,including physical trauma,noxious chemicals,as well as microbial agents.Uncontrolled inflammation is the pathological basis of multiple diseases,such as rheumatoid arthritis(RA),neurodegenerative diseases,liver disease,and lung inflammation.Lanostane triterpenoids are natural tetracyclic triterpenoids with significant anti-inflammatory activity.An extensive review of the published literature regarding the phytochemistry and anti-inflammatory pharmacology of lanostane triterpenoids has been performed and analyzed using several search engines,such as SciFinder,Web of Science,Scopus,PubMed,Google Scholar,and ScienceDirect.This review is devoted to naturally occurring lanostane-type triterpenes with anti-inflammatory activity,including their sources,biosynthesis,and mechanism of action.This review also discusses the inflammation-related diseases and the clinical significance of traditional Chinese medicine as multi-target therapeutic agents for the prevention and treatment of inflammatory diseases.In the past 30 years,more than 100 new lanostane-type triterpenes have been reported from the families Schisandraceae,Ganodermataceae,and Polyporaceae.Six compounds,fomitopinic acid A,fomitosides E and F,obtusifoliol,4α,l4α-dimethyl-5α-ergosta-7,9(11),24(28)-trien-3β-ol,and gramisterol exhibited the most potent anti-inflammatory activity against cyclooxygenase-1(COX-1)and COX-2,with IC50 values ranging from 0.087 to 1.15μM.Some of these compounds exhibited significant activity by mediating the inhibition of the pro-inflammatory cytokines,inducible nitric oxide synthase,and COX-2 expression.This review provides a basis for identifying anti-inflammatory drugs with high selectivity,high potency,and few adverse effects from lanostane-type triterpenes.