Studies On The Cross-coupling Reaction Between Chrial Nitrones And Carbonyl Compounds In The Presence Of SmI₂, And The Total Synthesis Of Swainsonine Epimers

Natural products which contain (3S,4R)-3,4-dihydroxy-pyrrolidine-ring possess a variety of important bioactivities and many of them show high potential for medical and biological application. Consequently, the asymmetric synthesis of these compounds have been a hotspot in organic synthesis field, and especially the synthesis of those compounds containing N-αhydroxyalkyl side chain is the most interesting research among them. For the polyhydroxylated alkaloids, such as (-)-swainsonine, a t effective retrosynthetic analysis involves the N-αhydroxyalkylation of (3S,4R)-3,4-dihydroxypyrrolidine.(?)A mild and high effective method to N-αhydroxylalkylation is pinacol-type coupling reaction between chiral nitrones and aldehydes (ketones) in the presence of SmI₂. Up to now, many of the researchs have focused on the reaction that the two gloup both in a chiral molecule or an intermolecular reactions between two achiral molecules. However, the research of pinacol-type coupling reaction between a chiral nitrones and aldehydes (or ketones), and its applications on asymmetric synthesis of natural alkaloids, remain challenging work and has not been reported.(?)One aim of this thesis was to develop the N-αhydroxyl-alkylation of (3S,4R)-3,4-dihydroxy-pyrrolidine in the presence of SmI₂, includes its application in the asymmetric synthesis of the indolizidine alkaloids (-)-swainsonine. The main results are listed as follows:1. In the presence of SmI₂, the pinacol-type cross-coupling reaction between the chiral nitrones 5 and aldehydes (ketones) was studied. Furthermore, different carbonyl compounds were attempted to react with the chiral nitrone 5 and derivatives in 49%-91% yields. Since the N-OH bond of the products could be easily cut off to give an amine, a high effective method for the synthesis of (3S,4R)-3,4-dihydroxy- pyrrolidine N-αhydroxyl-alkylation was established.(?)2. The asymmetric total synthesis of (-)-8a-epi-swainsonine 2 and (-)-8,8a-di-epi-swainsonine 3 have been achieved in an overall 39% (for 2: 24%; for 3: 15%) in four steps, through the pyrrolidine nitron N-αhydroxyl-alylation method.(?) (?)(-)-8,8a-di-epi-swainsonine 3 (-)-8a-epi-swainsonine 2(3S,4R)-3,4-Dihydroxyl pyrrolidine block is contained in many bioactive alkaloids. A feasible retrosynthetic analysis of the natural alkaloids such as DRB and (-)-swainsonine, both involve (3S,4R)-3,4-dihydroxyl-pyrrolidin-2-one. Thus it is significant to develop a compendious and high efficient method to synthesize (3R,4R)-3,4-dihydroxy-pyrrolidin-2-one.The another aim of this thesis is to establish a straightforward and feasible method to synthesize (3R,4R)-3,4-dihydroxy-pyrrolidin-2-one, starting from (-)-2,3-O- iso-propylidene-D-erythronolactone which is a facile and inexpensive material. Then we use the block to achieve the total synthesis of LRB (1,4-dideoxy-1,4- imino-L-ribitol). The results are listed follows: 1. Starting from (-)-2,3-O-isopropylidene-D-erythronolactone, the dihydroxy-protected (3R,4R)-3,4-dihydroxyl-pyrrolidin-2-one {4-Amino-4-deoxy-2,3-O-isopropy lidine-D-erythronolactam} was prepared in a total yield of 50% over 3 steps.(?)2. Starting from 4-amino-4-deoxy-2,3-O-isopropylidine-D-erythronolactam, asymmetric total synthesis of LRB (1,4-dideoxy-1,4-imino-L-ribitol) was achieved in 6 steps and in an overall yield of 58%.(?)...