Straightforward Synthesis of Labeled and Unlabeled Pyrimidine d4Ns via 2′,3′‐Diyne seco Analogues through Olefin Metathesis Reactions

Abstract

The synthesis of dideoxynucleosides (ddNs) or didehydro-dideoxynucleosides (d4Ns) from nucleosides has been extensively reviewed. While previously described methods are based on the modification of the 2Ј-and/or 3Ј-OH group of the intact ribose moiety, the use of a ring-closing metathesis (RCM) for the formation of the unsaturated cyclic system of nucleosides could be a straightforward approach to the d4Ns. Thus, as part of our drug labeling program, this paper reports

Structure Binding Relationship of Galactosylated Glycoclusters toward Pseudomonas aeruginosa Lectin LecA Using a DNA-Based Carbohydrate Microarray

“…This analogue was designed to may form additional hydrogen bonds between the heteroatoms of the thymine and the amino acid of the lectin leading to a possible better affinity. To this end, the azide derivative 4f was prepared according to a protocol described in the literature for the synthesis of glucose-thymidine . The 1,2,3,4,6-penta- O -acetyl- d -galactopyranose was glycosylated with 2,4-bis- O -trimethylsilyl-thymine affording the N 1 -(2′,3′,4′,6′-tetra- O -acetyl-β- d -galactopyranosyl)-thymine 15 (T-Gal) (Scheme ).…”

“…To this end, the azide derivative 4f was prepared according to a protocol described in the literature for the synthesis of glucose-thymidine. 53 For the synthesis of the new glycoclusters exhibiting either AcNPh-Gal or BuT-Gal motifs, the solid-supported mannose 7 was phosphorylated using either diethylene glycol propargyl phosphoramidite (1a), bis-pent-4-ynyl phosphoramidite (1b), or 2,2-(bis-propargyloxymethyl)propyl phosphoramidite (1c) (Scheme 4). Then, after oligonucleotide elongation and labeling, the tetra/octa alkyne constructions (17a−c) were conjugated to 4d affording the expected mannose-centered tetra/octagalactocluster oligonucleotide conjugates Man-(EG 2 MTzAcNPh-Gal) 4 G19, Man(ProTzAcNPh-Gal) 8 G21, and Man[THME(MTzAcNPh-Gal) 2 ] 4 G22, respectively, after ammonia treatment.…”

Synthesis of Pyranonucleoside‐6′‐triphosphates through the cycloSal‐Method

“…[16] 1,2,3,4,6-Penta-O-acetyl-d-galactopyranose (7; 2.00 g, 5.12 mmol) and thymine (646 mg, 5.12 mmol) were suspended in anhydrous MeCN (30 mL), N,O-bis(trimethylsilyl)acetamide (2.9 mL, 11.8 mmol) was added. [16] 1,2,3,4,6-Penta-O-acetyl-d-galactopyranose (7; 2.00 g, 5.12 mmol) and thymine (646 mg, 5.12 mmol) were suspended in anhydrous MeCN (30 mL), N,O-bis(trimethylsilyl)acetamide (2.9 mL, 11.8 mmol) was added.…”

Olefin Metathesis Route to Antiviral Nucleosides

“…While those methods are based onto the modification of 2'-and/or 3'-OH of the intact ribose moiety, the use of a RCM protocol, a promising tool in nucleoside chemistry [24,32,43], for the formation of the unsaturated cyclic system of nucleosides could be a straightforward approach to the d4Ns. Our team [44] reported a similar and optimized strategy for the synthesis of isotopically stable ( 13 C and 15 N)-d4T 80 from 13 C-labeled α-D-glucose (56) are of promising interest for pharmacokinetics studies by NMR. The key step of this chemical pathway is the formation starting from the hexonucleoside 57 of the dialdehyde 58 and its conversion into the diyne 59.…”