Chemoenzymatic arabinosylation of 2-aminopurines bearing the chiral fragment of 7,8-difluoro-3-methyl-3,4-dihydro-2H-[1,4]benzoxazines

Enzymatic synthesis of novel purine nucleosides bearing a chiral benzoxazine fragment

“…In the case of the ( S )‐configuration of the benzoxazine substituent, the rate of the ribosylation reaction of ( S )‐ 1 was lower than that for ( R )‐isomer. Earlier, we found that ( S )‐ 1 ‐arabinoside cannot be obtained using transglycosylation reaction (Eletskaya et al., ).…”

“…The method used to produce recombinant E. coli adenosine deaminase was described in Supporting information. Bases ( R )‐ 1 and ( S )‐ 1 (Eletskaya et al., ), ( R )‐ 2 and ( S )‐ 2 (Krasnov et al, ) were obtained according to the known procedures.…”

“…Preparation of adenine deaminase from E. coli ( Ec ADA) and determination of enzymatic activity are presented in Supporting information. Experimental data for the substrate specificity of adenosine deaminase E. coli ( Ec ADA) and ADA from calf intestine ( Ci ADA) with respect to nucleosides 3 – 6 , adenosine (Ado), 2′‐deoxyadenosine (2′‐dAdo), and 9‐(β‐ D ‐arabinofuranosyl)adenine (AraA), as well as previously synthesized arabinosides ( R )‐ 1 ‐Ara ( R )‐ 2 ‐Ara and ( S )‐ 2 ‐Ara, (Eletskaya et al., ), given in Table .…”

“…Recently, we have synthesized a number of 6‐substituted derivatives of purine and 2‐aminopurine containing amino acids (Krasnov et al., , ; Vigorov et al., ) and heterocyclic amines (Eletskaya et al., ; Gruzdev, Musiyak, Chulakov, Levit, & Krasnov, ) fragments. Among them, compounds with high antimycobacterial were found (Krasnov et al., ).…”

“…To obtain enantiomerically pure heterocyclic amines (the precursors of bases 1 and 2 ), the method of kinetic resolution of racemates was used (Gruzdev, Vakarov, Levit, & Krasnov, ; Gruzdev et al., ; Krasnov et al., ). Four bases of the series (conjugates of 2‐aminopurine with the enantiomers of 7,8‐difluoro‐3,4‐dihydro‐3‐methyl‐2 H ‐[1,4]benzoxazine [( R )‐ 1, 2 and ( S )‐ 1 , 2 ], (Figure ) were used in the enzymatic synthesis of β‐ D ‐arabinosides (Eletskaya et al., ). Unfortunately, bases 1 and 2 , as well as their arabinosides, did not show a high level of anti‐herpes activity in in vitro experiments on the HSV type‐1 model.…”