An Improved Study Of The Synthesis Of Phyllanthusols Agglutinin Precursor And Related Chemical Thermodynamics Calculations

Phyllanthusol A (4) and Phyllanthusol B (5) are new-style and high oxidized nonbisabolane compounds which was separated from the roots of P. acidus(Linn.)Skeel. These compounds showed obvious biological activitives, such as they are cytotoxic that can inhibit the BC and KB cell lines. These two new polyhydroxy myrrh sesquiterpene alkanes with spiro ketal structure element and complex chiral system structure are rare in nature, so there is important significance to synthesis it.This thesis first reported the synthetic conditions improvement for the compound 1,3-Dioxane-5-one derivatives’s, which are important precursor of 2,4-Dioxa-bicyclo [3.3.1] nonane (77). To synthesis compounds 1,3-Dioxane-5-one derivative (84,89), we first try to directly synthesis ketones from by dimer of 1,3-Dihydroxyacetone (82) and it monomer form (86), unfortunately, this route is not successful after various attempts. So we used glycerol instead to synthesize hydroxy compound 90, and then translated its hydroxyl group to carbonyl group by oxidation, and at last got the compound 2-Methoxy-l,3-dioxane-5-one (89) successfully.Later, we tried to asymmetric synthesis to introduce chiral center in our key intermediate 100,4-Phenyl-2-oxazolidinone (98-1) was choosed as the chiral auxiliary reagent for the asymmetric Aldol reaction. We screen the experimental conditions and hydroxyl protection groups selections, and at last got the compound 101 successfully.Then we used of ab initio method of the computational chemistry, the molecular structure of the above reactions by Gaussian software for geometry optimization and frequency analysis, following thermodynamic data to calculate the overall reaction. By the compare of relevant calculation data and actual experimental results, we found that the use of thermodynamic calculation method has some guidance and reference value for the design and concept of synthetic precursor compound.In the future work, we expect to complete the spiro ketal structure of Phyllanthusol. In addition, more different types of chiral auxiliary reagent and reaction conditions should be studied to introduce chiral center and ultimately synthesis the target compounds succesfully.All the structure of compounds reported in this thesis were all confirmed by and 13C-NMR spectrometer.