d-生物素的不对称全合成研究(Ⅴ)

Studies on the Asymmetric Total Synthesis of d-Biotin(Ⅴ)

以二异丁基氢化铝使 (3 a S,6a R) -1 ,3 -二苄基 -四氢 -4H-噻吩并 [3 ,4-d]-咪唑 -2 ,4(1 H) -二酮 (1 )高立体选择性地还原成 (3 a S,4S,6a R) -1 ,3 -二苄基 -4-羟基 -四氢 -1 H-噻吩并 [3 ,4-d]-咪唑 -2 (3 H) -酮 (2 ) ,再经缩合 ,Witting烯化成 (3 a S,6a R) -1 ,3 -二苄基 -四氢 -1 H-噻吩并 [3 ,4-d]咪唑 -2 (3 ) -酮 -4-烯戊酸 (4 ) ,后者经催化氢转移还原、脱苄即得 d-生物素 ,以化合物 1计算总产率为 42 % .

An efficient, high yielding and stereoselective synthesis of d biotin(6) is described. The stereoselective reduction of the known(3a S , 6a R ) 1,3 dibenzyl tetrahydro 4H thieno imidazol 2,4(1H) dione(1) with diisobutylaluminum hydride(DIBAL H) in toluene gave(3a S , 4 S , 6a R ) 1,3 dibenzyl 4 hydroxy tetrahydro 1H thieno imidazol 2(3H) one(2) in 91% yield with 99.7% e.e. . Alcohol 2 was directly converted into(3a S , 4 S , 6a R ) phosphonium salt 3 upon reaction with triphenylphosphine hydrogen tetrafluoroborate. Condensation of the corresponding ylide with 4 formylbutric acid afforded unsaturated acid 4. Catalytic hydrogen transfer hydrogenation of compound 4 with Pd D297 resin/ammonium formate system led stereoselectively to(3a S , 4 S , 6a S ) dibenzylbiotion(5), which was debenzylated by treatment with orthophospaoric acid in the presence of phenol to yield d biotin(6). The overall yield of d biotin was 42% from thiolactone 1.