A deamination-driven biocatalytic cascade for the synthesis of ribose-1-phosphate

Abstract

Ribose-1-phosphate (Rib1P) is a key substrate for the synthesis of difficult-to-access nucleoside analogues by nucleoside phosphorylases. However, its use in preparative synthesis is hampered by low yields and low selectivity during its preparation by conventional methods. Although biocatalysis permits straightforward access to Rib1P directly from natural nucleosides, these transformations are tightly thermodynamically controlled and suffer from low yields and non-trivial work-up procedures. To address these challenges, we developed a biocatalytic cascade that allows near-total conversions of natural guanosine into α-anomerically pure Rib1P. The key to this route is a guanine deaminase, which removes the accumulated guanine byproduct. Under optimised conditions, this cascade proved readily scalable to the gram scale, delivering isolated yields of up to 79% and a purity of 94% without any chromatography. Our cascade approach reduced the need for toxic reagents and purification steps inherent to previous methods, reducing the environmental burden of the route, as confirmed by CHEM21 Zero Pass and E-factor calculations. Thus, our work will broadly strengthen the applicability of nucleoside phosphorylase-mediated chemistry.