Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro

Abstract

A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of E. coli adenosine deaminase. The antiproliferative activity of the synthesized nucleosides was studied on human acute myeloid leukemia cell line U937. Among all the compounds, the serine derivative exhibited an activity level (IC50 = 16 μM) close to that of Nelarabine (IC50 = 3 μM) and was evaluated as active.

Intramolecular Hydrogen Bonding in N6-Substituted 2-Chloroadenosines: Evidence from NMR Spectroscopy

“…In the NMR spectra of substituted adenosines, the second form is usually registered as broadened signals at N 6 H-CH [16][17][18][19][20], or not registered at all. The NMR spectra of the purines with an electron-withdrawing substituent (Cl, F) at position 2 show the presence of the second form at room temperature [11], and the authors often do not discuss the second form, but it can be seen in NMR spectra in the Supplementary Information [21][22][23][24][25][26]. Various C2-substituted purines with optically active substituents at C6 were obtained.…”