Bis- and Trisuracil Nucleosides with Nucleobases Anchored to 11-, 12-, and 16-Membered Macrocyclic Scaffolds:  Synthesis and Aggregation Study

Abstract

Bis- and trisuracil nucleosides, in which the nucleobases are anchored to isoxazoline ring-fused 11-, 12-, and 16-membered macrooxacycles, were synthesized by nucleosidation of 1,2-isopropylidenefuranose ring-fused macrocycles. The nucleosides exhibited spherical and fiber-like morphologies in water. In one case, the morphology was significantly altered by complexation with an adenine nucleoside via complementary base pairing.

Synthesis and Applications of Carbohydrate-Derived Macrocyclic Compounds

“…These compounds were derivatized to the corresponding cyclic bis- and trisuracil nucleosides 834 – 836 by isopropylidene deprotection, acetylation, and N -glycosylation with uracil, in the presence of BSA and TMSOTf (Scheme ) . These nucleoside-functionalized macrocycles exhibited interesting aggregation properties in water, as revealed by TEM, with various morphologies such as spheres, fibers, rods, or nanotubes depending on the concentration and on the presence of a complementary adenine nucleoside 837 …”

Transglycosylation Reaction: Synthesis and Supramolecular Study of Carbohydrate‐Cased C2‐Symmetric 20‐ and 22‐Membered Macrocyclic Dinucleosides

“…Deprotection of 1, 2‐position of CSM‐1 with 4 % aqueous mineral acid (H 2 SO 4 ) followed by acetylation gave diastereomeric mixture of acetylated products 9 , which was evident from proton‐NMR.Treatment of acetylated compounds with uracil and thymine in the presence of N , O ‐bis(trimethylsilyl)acetamide (BSA) and trimethylsilyl triflate (TMSOTf) led to the uracil ribonucleoside 10 , [25] thymine ribonucleoside 11 [25] in 65 % and 44 % yields, respectively (Scheme 2). The structures of 10 and 11 was established by 1 H and 13 C NMR spectra.…”

“…The C 2 -symmetric macrocycles CSM-1, CSM-2, CSM-3 and CSM-4 were synthesised following the known protocol. [25] The C 2 -symmetric macrocyclic nucleosides 3, 4, 5, 6, 7, 15 and 16 were synthesized from the above mentioned macrocycles by Vorbruggen transglycosidation method. On the other hand, the monosugar unit derived from hydrolysis of CSM-1, on nucleosidation give rise to nucleosides 10, 11 and 12.…”

Ring-Closing Metathesis and Glycosylation Reactions: Synthesis and Biophysical Studies of Polyether-Linked Carbohydrate-Based Macrocyclic Nucleosides

“…Using a ring-closing-metathesis(RCM)-based strategy on a carbohydrate backbone using a Grubbs catalyst has been considered a useful method for the construction of difficult-to-access cyclic rings of varied sizes present in naturally occurring bioactive compounds, conformationally restricted β-turn mimics, and cyclic nucleosides and nucleotides . However, very few carbohydrate-based macrocyclic nucleosides with polyether linkages (crown-ether-type) are known in the literature. , Therefore, we made sustained efforts to build an array of diverse macrocycles and their nucleoside analogues to find out their important properties. The strategy was to synthesize them from easily available carbohydrates via operationally simple routes that are fundamentally different from the methods routinely exploited.…”