N-Phosphorylated Serine Model For Chemical Origin Of Glycerophosphatide And Gold (Ⅰ)-Catalyzed Chiral Homopropargyl Sulfonamides Tandem Reaction

This thesis mainly completes two parts of work:The first part is based on the N→O migration reaction of N-phosphatidylserine to study the chemical origin of glycerophospholipids in cell membrane.The second part is the research on gold(Ⅰ)-catalyzed isomerization cascade reaction for the synthesis of chiral pyrrolidine derivatives.The specific two contents are as follows:In the first part,based on the CAPA intermediate of N-DIPP-Ser,the chemical reaction between N-phosphorylated serine and glycerol was explored.The solvation effect of N-phosphatidylserine and glycerol was found to be significant,and the molecular mechanism of various solvation effects was explained from the Berry pseudorotation(BPR)process of the key reaction intermediate CAPA.By optimizing the synthesis method,we obtained a five-membered cyclic glycerophosphate ester with 84%yield in acetonitrile.Then we also achieved a six-membered cyclic 1,3-glycerophosphate ester with isolated yield of 88%,when using DMF instead of acetonitrile.Besides,an undesired O-DIPP-Ser-glycerine was observed with 97%yield in 31P nuclear magnetic resonance with glycerol as a solvent.In addition,we also explored the purification methods for the polar glycerophosphoric acid derivatives and developed a separation technique based on ODS C18 reversed-phase column chromatography.With cyclic 1,3-glycerophosphate ester in hand,we further optimized the initial design,and synthesized diverse glycerophospholipids.we got glycerophosphatidylethanolamine(GPE)with a yield of 36%,when cyclic 1,3-glycerophosphate ester reacted with ethanolamine.We then use the same stateg-y for the synthesis of glycerophosphatidylcholine(GPC),finally obtain its pure product with a yield of 43%.Considering the stereoselectivity of sn-3-glycerophosphoryl-L-serine(a-GPS),1,3-glycerophosphate ester was reacted with L-serine,and calcium chloride was used as an additive at the same time,resulting in a stereogenic configuration of a-GPS with a yield of 47%.Further more,PS and lyso-Ps were observerd from a mixture of a-GPS,palmic acid and kieselguhr.With these achievements,N-phosphoserine considerd as a chemical evolutionary model of phospholipids is proposed,which provides a new research perspective for the hypothesis "common origin regulated by N-phosphorylated amino acids".In the second part,a novel strategy on the gold(I)-catalyzed cycloisomerization/dimerization cascade reaction of chiral homopropargylamine was carried out.18 highly stereoselective pyrrolidine diastereomers were obtained with a yield of 75%-92%(Chapter 4).The chapter 5 is based on the homogeneous gold(Ⅰ)-catalyzed hydroamination reaction for the synthesis of chiral 2,3-dihydropyrrole compounds.19 kinds of high stereoselective 2,3-dihydropyrrole derivatives are obtained with a yield of 91%-99%.This synthetic strategy is further used in the synt hesis of the natural base(+)-preussin precursor.In the sixth chapter,a new strategy combined the gold(I)catalyst with organic reductive reagents for the synthesis of chiral pyrrolidines is carried out.20 highly stereoselective pyrrolidine enantiomers were obtained with a yield of 90%-99%.With this synthetic strategy,alkaloids(-)-irniine,(-)-bgugaine,and S-MMP were efficiently constructed.This synthetic methodology has broad application prospects,due to the high catalytic activity of gold(Ⅰ),mild reaction conditions,and satisfactory compatibility of chemical groups.