The Skeleton Construction Research Of Highly Oxygenated Norbisabolane Compounds

Highly oxygenated norbisabolane compounds are a class of bisabolane sesquiterpene compounds with the similar spiro ketal structure.At present,the compounds with these characteristic structures discovered from nature were comparatively rare.Most of them showed some biological activitives and several reports on their synthetic studies were published.Phyllanthusol A and B are one of these kinds of compounds and were isolated from the root of Phyllanthus acidus by Prasat Kittakoop in 2000.They showed cytotoxic activity.Phyllanthusol A and B could be hydrolyzed to yield the norbisabolane aglycon and the saccharide residue by basic solution.The glycoside compounds belong to highly oxygenate nor-bisabolane.This thesis reported the studies of skeleton constructions of this highly oxygenate nor-bisabolane.First of all,we synthesized two important intermediates,cis-3,5-two-hydroxy-4-carbonyl methyl formate derivative 102 and dihydroxy methyl ketone derivative 108-1 by a mature route from our group.But we could not obtain the desired compound with whole skeleton structure,no matter we try to connect these two fragments by aldol condensation,Mukaiyama aldol and relative condensations.We thought that the protecting group of 108-1 was not stable enough and try to chang it to others.When we try to protect the hydroxy with benzyl,we found that the CH2 between the hydroxyl and carbonyl was very easy to form carbon anion under strong base.This suggested that a-methyl group in the carbonyl compounds should be more acidic for our subsequent synthesis.Later,we redesigned the synthetic route.Cis-3,5-two-hydroxy-4-carbonyl methyl formate derivative 102 and 6-benzyl-4-hydroxy-5-methyl-2-carbonyl-demethyl hexylphosphonate(157)were two important intermediates of the route.Finally,we obtained the compound 106 with good yield from compounds 157 and 102 by HWE reaction.Compound 106 contained all the carbon skeleton of our target molecule Phyllanthusols.But our structural modification for further synthese was failed.In future work,we will try to finish our synthese work from compound 106.We will also try the asymmetric synthesis of aglycone moiety through the chiral starting material or chiral auxiliary.All the structures of compounds reported in the synthesis were characterized by H-NMR and 13C-NMR spectrometer.