Chemo-enzymatic syntheses of natural and unnatural 2′-deoxynucleosides

A chemo-enzymatic method for preparations of natural and unnatural deoxynucleosides was developed. The method consists of chemical synthesis of natural and unnatural deoxyribose 1-phosphates and their enzymatic conversion to deoxynucleosides. A highly stereoselective synthesis of 2-deoxyribose 1-phosphate was first achieved by an unprecedented application of crystallization-induced asymmetric transformation. Additionally, we first discovered a 2′-deoxycytidine producing enzyme. The discovery and the development of a scalable synthetic process of 2-deoxyribose 1-phosphate enabled us to manufacture all four natural 2′-deoxynucleosides practically. The methodology was applied to the synthesis of 2′,3′-dideoxy-3′-fluoroguanosine via synthetic 2,3-dideoxy-3-fluororibose 1-phosphate.