Stereoselective And Enantioselective Synthesis Of Trans-2, 5-disubstituted Tetrahydrofurans

Platelet-Activating Factor (PAF) was discovered as a powerful platelet-stimulating agent which leads to some diseases, e.g. inflammation. Researching antagonists of platelet activating factor is one of the most important tasks of the medicine in the world today. Natural 2,5-disubstituted tetrahydrofiiran series ,whose resources are limited, were identified as competitive PAF-receptor antagonists. There are problems in some synthetic processes, for example, low yields, difficult separation of stereoisomers and /or poor stereoselectivity. The key problem is to synthesize high stereoselectively trans- 2,5- disubstituted tetrahydrofurans. This thesis sets up a new method to synthesize stereoselectively ?ra玸--2,5-disubstituted tetrahydrofurans by introducing two alkyl(aryl) groups in 3-C and 5-C of lactol, flash decomposition and hydrogenation. MK-287 analogues, (2S,5S) and (2R,5R)- trans-2,5-diaryl tetrahydrofurans, are synthesized enantioselectively by a serieous of reactions of addition, oxidation, addition, reduction, flash decomposition and hydrogenation from (-)-lactol or (+)-lactol . the optic purity of MK-287 is 100 %. (2S,3S,4R)-2-n- pentyl-3,4-dihydroxy tetrahydrothiofuran is synthesized from (+)-lactol by six steps: addition, sulfonylation by TsCl, cyclization, flash decomposition, oxidation and hydrogenation. This work present a new process to synthesize some chiral five-membre hetrocyclocompounds, such as MK-287, antagonists ofPAF, and biotin or deoxybiotin.