Total Synthesis Of 4-Hydroxytrilobin And Study On Syntheses And Activities Of Thienopyrimidine Derivatives

This research project is mainly focused on (1) total synthesis of 4-Hydroxytrilobin; (2) cleavage of terminal epoxides toβ-halohydrins using active magnesium halides with high reigoselectivity; (3) syntheses and activities evaluation of thienopyrimidine derivatives and (4) L-proline-catalyzed Gewald reaction for the preparation of 2-aminothiophenes.In this section, the aldehyde 10 and the terminal alkyne 17 are prepared from (S)-glycidyl and (D)-mannitol, respectively. Next, some chiral centers of target molecule are obtained from the asymmetric addition reactions of the compound 17 with the compound 10 and 25, respectively, controlled by the chiral ligand 20. And the key fragment of bis-THF ring is prepared through some reactions. Finally, the unsuccessful attempt on the coupling of fragment 34 and 35 may be owing to the low subtrate loading, and further synthesis is going on.At the same time, a new exploration on the fragment of bis-THF ring using asymmetric Aldol reaction catalyzed by D-proline as a key step has been developed. The compound of mono-THF ring 50 is obtained, and further exploration is going on.The second section describes an efficient, practical procedure for the transformation of terminal epoxides into P-halohydrins with high regioselectivity using active magnesium halides. This procedure features good functional-group tolerance, considerably fast reaction and high yielding.Four series of various phenols and anlines substituted thienopyrimidine derivatives have been designed and synthesized according to the structure of lead compound in the third section. Initial screening of GPR40 receptor antagonist with the A series of compounds has been done, and the results show that the activities of two compounds (A-10 and A-15) are better.The last section communicates an efficient and convenient L-proline-catalyzed Gewald reaction in one-pot technique for the synthesis of 2-aminothiophenes, and this protocol features more convenient and efficient procedure using lower catalyst loading (10 mol%) with high yields, comparing to the traditional Gewald reaction conditions using 50～100 mol% or even more catalyst loading.