Asymmetric Construction of Substituted Purine Esters with Tunable N‐9/N‐7 Regioselectivity via Enzymatic Dynamic Kinetic Resolution

Abstract

We report an enzyme‐catalyzed dynamic kinetic resolution protocol for the one‐pot asymmetric synthesis of substituted purine derivatives with high product yield (up to 96%) and enantio purity (up to 99%). The controllable N‐9/N‐7 substitution, which posed formidable challenges in organic synthesis, could be accomplished by choosing different types of enzymes as the catalyst. This method was proved easily scalable and was successfully used to prepare a series of prodrugs of medicinally active acids. In addition, the biocatalysts exhibited good recyclability, indicating the potential of this strategy for practical applications in the pharmaceutical industry.

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“…An enzyme catalysed dynamic kinetic resolution (DKR) method has been reported for the one-pot asymmetric synthesis of substituted purine derivatives. 32 Following reaction of the purine with aldehydes, combined acetyl transfer and DKR using lipase from Thermomices lanuginosus (TL-IM, immobilised on maltodextrin) gave the substituted purines in high yields and excellent enantioselectivity (Scheme 5). Using different enzymes, the position of purine substitution (N-9 versus N-7) could also be controlled.…”