TY - JOUR A1 - Kumar, Sandeep A1 - Maity, Jyotirmoy A1 - Kumar, Banty A1 - Kumar, Sumit A1 - Prasad, Ashok K. T1 - Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues JF - Beilstein Journal of Organic Chemistry PY - 2022/// VL - 18 SP - 95 EP - 101 SN - 1860-5397 DO - 10.3762/bjoc.18.10 PB - Beilstein-Institut JA - Beilstein J. Org. Chem. UR - https://doi.org/10.3762/bjoc.18.10 KW - bicyclic AZT analogues KW - bridged homoarabinofuranosylpyrimidine nucleosides KW - chemical pathway KW - Lipozyme® TL IM KW - regioselective enzymatic acetylation N2 - Conformationally restricted diastereomeric homoarabinofuranosylpyrimidines (AZT analogue), i.e., (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosylthymine and -uracil had been synthesized starting from diacetone ᴅ-glucofuranose following chemoenzymatic and chemical routes in 34–35% and 24–25% overall yields, respectively. The quantitative and diastereoselective acetylation of primary hydroxy over two secondary hydroxy groups present in the key nucleoside precursor was mediated with Lipozyme® TL IM in 2-methyltetrahydrofuran following a chemoenzymatic pathway. Whereas, the protection of the primary hydroxy over the lone secondary hydroxy group in the key azido sugar precursor was achieved using bulky tert-butyldiphenylsilyl chloride (TBDPS-Cl) in pyridine in 92% yield following a chemical synthetic pathway. The chemoenzymatic method was found to be superior over the chemical method in respect of the number of synthetic steps and overall yield of the final product. ER -