STRUCTURE AND REACTION OF ARTEANNUIN

Arteannuin (1) ,a new sesquiterpene containing a peroxide group,has beenisolated from Artemisia annua L.It crystallizes in colorless needle.The high resolutionmass spectrum indicated the moleculer formula,C_(15) H_(22) O_5. Its infra red spectrum showsa δ-lactone group at 1745cm~(-1) and a peroxide group at 831,881,1115cm~(-1) .The NMRspectrum of Arteannuin (1) has a tertiary methyl group at δ 1,36 and two secondarymethyl group at δ0. 93 (J=6 Hz) and δ 1. 06 (J=6. 5 Hz) respectively and a multipletat δ3. 08～3. 44. A sharp proton singlet at δ5. 68 is assigned to an acetal hydrogen.Irradiation of the multiplet proton at δ3. 08～3. 44 in the spectrum of (1) causes threeproton doublet at δ1. 06 to collapse to a singlet.Furthermore,irradiation of the methylgroup signal at δ1. 06 causes the multiplet at δ3. 08～3. 44 to change into an oneproton doublet (J=4. 5Hz) which can be assigned to a proton on the carbon adjacentto methyl group and it appears clearly that only one proton is attached to the adjacentcarbon.The wide band ~1H decoupled at ~(13) C NMR data of Arteannuin (1) has 15 carbonresonances.The off resonance ~(13) C NMR data allows the observed resonances to beassigned to three methyl-,four methylene-,five methine-and two quaternary carbonstogether with one carbonyl-carbon.The presence of peroxide group is further proved by quantitative reaction withtriphenyl phosphine.Catalytic hydrogenation of Arteannuin (1) over palladium-calcium carbonate catalyst yields the epoxy compound (2) with loss of one oxygenatom.When compound (1) is reduced with sodium borohydride,it gives the hydroxycompound (3) which can be further hydrogenated under the above mentioned conditionto yield compound (4) .Compound (4) also obtained by reduction of compound (2)with diisobutylaluminum hydride can be reoxidized with chromic anhydride-pyridineinto compound (2)The partial structures Ⅰ,Ⅱ,Ⅲ,Ⅳ and Ⅴ have been deduced by the chemicaland spectroscopic evidences.The structure and relative configuration was ultimatelydetermined by X-ray diffraction The structure picture of Ⅰ is shown in Figure1. The trans configuration of the lactono ring was deduced as (1) by comparison of its ORD spectrum with that of compound (6) obtained from arteannuin B.Theabsolute configuration of arteannuin (1) was determined using anomalous dispersionof Cu-radiation by oxygen atoms and was shown in 1. Stereoview of 1 is shown inFigure 1.It is known that the reduction of dialkyl peroxides to the corresponding alcoholsand/or ethers may be carried out with a variety of reducing agents such as titaniumtrichloride,lithium aluminum hydride and hydrogen with catalysts.Arteannuin(1) furnished the dihydroxy compound (A) in catalytic hydrogenation over palladiumcalcium carbonate,and underwent deacetalization to give unstable compound (B)whichquantitatively converted into the lactone (2) ,in the presence of trace amount of acid.Its formation may be considered as a result of an intramolecular ketal and acetel for-mation.Arteannuin (1) on treatment with potassium carbonate in methanol at roomtemperature for an hour undergoes an intramolecular epoxidation to give the α-epoxide(10) .The hydrogenolytic product (2) is converted by 10% alcoholic potassium hydro-xide solution at room tempereture through a keto-aldebyde reaction into α,β-unsaturat-ed ketone(9) which on treating with 30% hydrogen peroxide affords the β-epoxide(11) .From the NMR spectra of 10 and 11 (Table 2) it is evident that H-4 of β-epo-xide undergoes the rather down field shift arising from deshieding effect of the lactonecarbonyl group,since from the molecular model the H-4 seems much closer to thelactone ring.With 10% sulfuric acid in glacial acetic acid at room temperature,Arte-annuin (1) gives the compound (16) .This reaction seems to proceed through a carbo-nium-ion intermediate (12) formed by carbon-oxygen fission in acid.Compound (16)on treatment with dilute alkali gives α,β-unsaturated carbonyl compound (17) ,whichon further acidification is retransformed into the original compound (16) .This furtherproves that the γ-lactone ring of compound(16) is in the cis-form,because the forma-tion of cis lactone ring is much easier then the trans one.Compound (17) on treat-ment with triethyl oxonium fluoroborate gives the ethyl ester of(18) .Since its opticalrotatory dispersion coincides with that of compoud (19) ,therefore,the C_1-H ofArteannuin (1) is also α-orientated.