CAJ | 학술논문

以商业化易得的具有碱性氮原子的手性药物为有机催化剂,用于催化β-酮酸酯不对称α-羟基化反应,发现以噻吗洛尔或普萘洛尔为催化剂,反应对映选择性分别可达32%和18%.对噻吗洛尔和普萘洛尔进行结构修饰,合成了12个洛尔药物类似物,并考察了其催化效果,发现在优化的反应条件下,以30 mol%(R)-1-叔丁胺基-3-(2-萘氧基)-2-丙醇(7f)为催化剂,20 mol%β-环糊精为助催化剂,叔丁基过氧化氢为氧化剂,正己烷为溶剂,反应对映选择性最高可达57%,收率92%.不对称α-羟基化产物(S)-5-氯-2-羟基-1-茚酮-2-甲酸甲酯(2a)在乙酸乙酯中一次重结晶后,对映体光学纯度可达99%,收率68%.
이상업화역득적구유감성담원자적수성약물위유궤최화제,용우최화β-동산지불대칭α-간기화반응,발현이새마락이혹보내락이위최화제,반응대영선택성분별가체32%화18%.대새마락이화보내락이진행결구수식,합성료12개락이약물유사물,병고찰료기최화효과,발현재우화적반응조건하,이30 mol%(R)-1-숙정알기-3-(2-내양기)-2-병순(7f)위최화제,20 mol%β-배호정위조최화제,숙정기과양화경위양화제,정기완위용제,반응대영선택성최고가체57%,수솔92%.불대칭α-간기화산물(S)-5-록-2-간기-1-인동-2-갑산갑지(2a)재을산을지중일차중결정후,대영체광학순도가체99%,수솔68%.
Using commercially available, basic nitrogen atom containing chiral drugs as the organocatalysts for asymmetric α-hydroxylation of β-keto esters, it was found that the enantioselectivity reached 32% and 18% when using timolol and propranolol as the organocatalyst, respectively. The structures of timolol and propranolol were then modified and twelve analogs were synthesized to investigate the catalysis perform-ance. It was found that under the optimized reaction conditions, using 30 mol% of (R)-1-(tert-butylamino)-3-(naphthalen-2-yloxy)propan-2-ol (7t) as the organocatalyst, 20 mol% of β-cyclod-extrin as the cocatalyst, tert-butyl hydroperoxide as oxidant and n-hexane as solvent, the enantioselectivity reached up to 57% with the yield of 92%. The ee value of (S)-methyl-5-chloro-2-hydroxy-l-oxo-2,3-dihydro-1H-indene-2-carboxy-late (28) reached up to 99% with the yield of 68% after a single recrystallization from ethyl acetate.