Development and Application ofEnzymatic Asymmetric Synthesis ofFunctionalized Alcohols

Sammanfattning: The main focus of this thesis lies on enzymatic asymmetric organic reactions. In the first part ofthis work, we looked into the lipase-catalyzed transesterification and hydrolysis at the molecularlevel. It was shown that the low enantioselectivity of CALB-catalyzed transesterification of a δ-functionalized alkan-2-ol to its acetate does not correlate at all with the high enantioselectivity ofthe CALB-catalyzed hydrolysis of the corresponding acetate in water. This lack of correlation isunusual and for unfunctionalized alkan-2-ol derivatives there is a very good correlation betweenthe enantioselectivity of transesterification of the alcohol and hydrolysis of the correspondingacetate with a high enantioseletivity in both cases. The results confirm previous predictions frommolecular modeling. The water effect was mimicked by CALB variant Ala281Ser, whichshowed an enhanced enantioselectivity in transesterification of δ-functionalized alkan-2-olscompared to wild type CALB.In the second part of the thesis, enzymatic kinetic resolution to resolve 1-substituted buta-2,3-dien-1-ol was studied. The initial goal was to use Shvo catalyst as racemization catalyst for anenvisioned dynamic kinetic resolution of this substrate. To our surprise, 2,3-dihydrofurans wasformed when α-allenic alcohols was treated with Shvo catalyst and the chiral center that endedup in the product was unchanged. Based on the KR and cycloisomerization, we furthermoredeveloped a one-pot procedure combining kinetic resolution and cyclization to optically pureoxygen-containing heterocycles. The mechanism of the Ru-catalyzed cycloisomerization wasstudied and a Ru-carbenoid was suggested as a crucial intermediate for forming the 2,3-dihydrofurans.