The Synthesis Of Digitoxin And Fucose Oligosacharides

The article includes three parts. The first, a steroselective and regioselective synthesis of digitoxin with glycosyl ortho-alkynylbenzoates as doners. The second, synthesis of different length chain of L-fucose with a SO3Na group in the position of C-2 hydroxy. The third, improve an existed route to synthesis voglibose.1. The article used two methods to synthesis all Ac protected cymarose glycosyl ortho-alkynylbenzoates doner 16 (in liner 10 steps, 21.5% yield in total) and MBz and Ac protected cymarose glycosyl ortho-alkynylbenzoates doner 34 (in liner 11 steps, 45.7% yield in total) from methyl glucose. Compound 15 and 17 were used to synthesis Schimidt and trifluoroacetimidates glycosyl doner but unfortunately they couldn't work at all in different solvent ( DCM and Acetone) and using all common used base(DBU, NaH and k2CO3). Degration of digitoxin with 5% H2SO4 / CH3OH in 85% yield to get Digitoxigenin 36. Under the catalyst of PPh3AuOTf, glycosyl doner 34 and glycosyl acceptor in mixed solvent (DCM : Tol = 2 : 1) at suitable temperature and in appropriate experiment operation got the target digitoxin 1 and its monosachride derivate 39 and dissacharide derivates 46. In the process of experiment, selectively cleave of Ac protection became a big problem. Using LiOH / NH3 / DBU / Bu2SnO / (Bu3Sn)2O / NaOMe in different solvent (THF, CH3OH, H2O et al) couldn't get ideal result. Having no alternate, cleaving all protection groups, using regioselective glycosation method got the expected effect. The regioselectivity was 6 : 1 and steroselectivity was 8 : 1 in the process of experiment to get compound 45 and 47. At last, complete the synthesis of digitoxin in liner 17 steps in 16.2% yield. 2. L-fucose, as raw material, protected with ortho ester, synthesized the glycosyl acceptor 60, 76, thioglycoside doner 57,61,62, fluorglycoside 65,66 and Schimidt doner 68, 70 in a simple and efficient way. Thioglycoside doner was promoted by NIS / AgOTf and Tf2O / BSP (or DPSO) / TTBP; fluorglycoside and thioglycoside acceptor 60 were condensed in ideal yield to get 88; Schimidt doner was promoted by TMSOTf. In the process of our work, we got the fucose chain from 4 to 7 sacharide (84,87,98,99) in ideal yield and excellent steroseclectivity with linear strategies glycosylation and convergent block synthesis. Unfortunately, sectively cleave of Bn protection group became a shackle and couldn't be overcome though we used all known methods. After that, changing the Ac group with other group made it possible and we had got the desired product. The newly designed route was finished by another colleague.3. the improved synthesis of voglibose was described. The glucose, as raw material, underwent glycuronic inner ester 109, cyclohexanone 113 and amination reduction important process to afford the target product in 13 steps. This improved route gave a good yield 23.5% in total. This work reduces the production cost, makes the experiment operation simple and can be apply in the large-scale production.