Crystal structures of the synthetic intermediate 3-[(6-chloro-7H-purin-7-yl)methyl]cyclobutan-1-one, and of two oxetanocin derivatives: 3-[(6-chloro-8,9-dihydro-7H-purin-7-yl)methyl]cyclobutan-1-ol and 3-[(6-chloro-9H-purin-9-yl)methyl]cyclobutan-1-ol

Abstract

The crystal structures of an intermediate, C10H9ClN4O, 3-[(6-chloro-7H-purin-7-yl)methyl]cyclobutan-1-one (I), and two N-7 and N-9 regioisomeric oxetanocin nucleoside analogs, C10H13ClN4O, 3-[(6-chloro-8,9-dihydro-7H-purin-7-yl)methyl]cyclobutan-1-ol (II) and C10H11ClN4O, 3-[(6-chloro-9H-purin-9-yl)methyl]cyclobutan-1-ol (IV), are reported. The crystal structures of the nucleoside analogs confirmed the reduction of the N-7- and N-9-substituted cyclobutanones with LiAl(OtBu)3 to occur with facial selectivity, yielding cis-nucleosides analogs similar to those found in nature. Reduction of the purine ring of the N-7 cyclobutanone to a dihydropurine was observed for compound (II) but not for the purine ring of the N-9 cyclobutanone on formation of compound (IV). In the crystal of (I), molecules are linked by a weak Cl...O interaction, forming a 21 helix along [010]. The helices are linked by offset π–π interactions [intercentroid distance = 3.498 (1) Å], forming layers parallel to (101). In the crystal of (II), molecules are linked by pairs of O—H...N hydrogen bonds, forming inversion dimers with an R22(8) ring motif. The dimers are linked by O—H...N hydrogen bonds, forming chains along [001], which in turn are linked by C—H...π and offset π–π interactions [intercentroid distance = 3.509 (1) Å], forming slabs parallel to the ac plane. In the crystal of (IV), molecules are linked by O—H...N hydrogen bonds, forming chains along [101]. The chains are linked by C—H...N and C—H...O hydrogen bonds and C—H...π and offset π–π interactions [intercentroid distance = 3.364 (1) Å], forming a supramolecular framework.

Keywords

• crystal structure
• oxetonacin
• cyclobutanone
• cyclobutanol
• HIV
• hydrogen bonding
• offset π–π interactions
• supramolecular framework