Study On The Chemical Constituents And Their Biological Activity Of The Medicinal Plant Clerodendranthus Spicatus

The chemical constituents for the aerial parts of the medicinal plant Clerodendranthus spicatus were isolated by means of various chromatographic methods including normal-phase silica gel column chromatography（CC）,Sephadex LH-20 CC,analytical&preparative HPLC,etc.Their structures were elucidated by extensive spectroscopic methods including 1D&2D NMR,HRMS,IR,UV,and ORD.As a result,43 compounds were isolated and identified,including 17 previously undescribed compounds.The new compounds contain 15 isopimarane-type diterpenes including clerodendranthins A-O（1-15）and two linear sesquiterpenes of 2,6,10-trimethyldodeca-6,11-diene-2,3,5,10-tetraol（16）and（2E,7E）-6,10-dihydroxy-2,6-dimethyldodeca-2,7,11-trienal（17）.The known compounds were identified as orthosiphonnones A（18）and B（19）,orthosiphols M（20）and N（21）,3-O-deacetylorthosiphols I（22）and J（23）,orthosiphols A（24）,B（25）,G（26）,K（27）,O（28）,P（29）,V（30）and W（31）,orthosiphol R（32）,6-hydroxyorthosiphol B（33）,neoorthosiphols A（34）and B（35）,nororthosiphonolide A（36）,orthosiphol Q（37）,axillactone B（38）,loliolide（39）,5-hydroxy-3,4-dimethyl-5-pentylfuran-2（5H）-one（40）,chensianol A（41）,（Z）-6-（（2R）-5-（2-hydroxypropan-2-yl）-2-methyltetrahydrofuran-2-yl）-3methylhexa-1,5-dien-3-ol（42）and（E）-4-（（1R,4R,6S）-4-hydroxy-2,2,6-trimethyl-7-oxabicyclo[4.1.0]heptan-1-yl）but-3-en-2-one（43）.Compounds 7-15 possess an unusual moiety with a nitrogen-containing side chain.They represent the first cases of isopimarane diterpenes from C.spicatus.These compounds were subjected to evaluate their immunosuppressive activity and anti-inflammatory production activity by the lymphocyte proliferation assay and their anti-NO production functions.The ³H-thymidine incorporation assay on the murine lymphocyte proliferation showed that compounds 10 and 35 significantly inhibited the proliferation on T lymphocytes with IC₅₀ values of 1.84（select index,SI=15.7）and 1.37μM（SI=277.9）,respectively.Compound 35 also selectively inhibited the proliferation on B lymphocytes with an IC₅₀ value of 8.7μM（SI=43.9）.The anti-NO production assay on RAW 264.7 macrophages suggested that compounds 9,26,34 and 35 showed weak inhibition on NO production with IC₅₀ values of 40.1,41.3,49.7 and 35.9μM.In addition,compound 14 showed cytotoxicity against the RAW 264.7 macrophages.In addition,two cadinene-type sesquiterpenoids rigidoporones A（44）and B（45）,a racemic alkaloid（?）-rigidoporine A（46）were isolated from the rice fermentation of the wood-decay fungus Rigidoporus microporus.The structures of the compounds were established by extensive spectroscopic methods,including 1D&2D NMR and HRMS spectroscopic analysis.