Reaction Kinetics and Mechanism of Sulfuric Acid‐Catalyzed Acetolysis of Acylated Methyl L‐Ribofuranosides

Abstract

The mechanism of the sulfuric acid‐catalyzed acetolysis of methyl 2,3,5‐tri‐O‐acetyl‐ and methyl 2,3,5‐tri‐O‐benzoyl‐L‐ribofuranosides and the accompanying anomerization of both the starting material and the 1,2,3,5‐tetra‐O‐acetyl‐ and 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐L‐ribofuranoses formed was investigated. The progress of the reactions was followed by 1H NMR spectroscopy and the rate constants for the reactions were determined for a proposed kinetic model. The role of H+ and Ac+ as the catalytically active species was clarified, proving that the anomerization of the acylated methyl furanosides is activated by protonation, while, on the contrary, the anomerization of the 1‐O‐acetyl ribofuranoses is activated by the acetyl cation. The anomerization of the acylated methyl furanosides was verified to be activated on the ring oxygen leading to endocyclic CO‐bond rupture while the 1‐O‐acetyl ribofuranoses are activated on the acetyloxy group on C(1) leading to exocyclic cleavage.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis and evaluation of N-alkylated analogues of aza-galacto-fagomine – potential pharmacological chaperones for Krabbe disease

“…NMR data was in accordance with previously reported values. 24 Methyl 2,3,5-tri-O-benzyl-L-ribofuranoside (11α and 11β). The crude methyl L-ribofuranoside (10) (7.56 mmol) was dissolved in anhydrous DMF and cooled to 0 °C.…”

“…R f ( pentane/ethyl acetate 2 : 1) 0.18; 1 H-NMR (400 MHz, CDCl 3 ): δ H 7.41-7.07 (m, 14.8H), 4.99 (q, J 4.9 Hz, 0.5H), 4.93 (q, J 5.4 Hz, 0.3H), 4 Complicated spectrum due to a mixture of rotamers (3R,4S,5R)-1-N-Palmitoyl-3-benzyloxymethyl-4,5-di-O-benzyl-4,5-dihydroxyhexahydropyrizadine (24). The crude mesylate 20 (0.948 mmol) was dissolved in anhydrous nitromethane (8 mL), added N,N-diisopropylethylamine (0.49 mL, 2.86 mmol, 3 eq.)…”

Reaction mechanisms : Part (iii) Polar reactions

“…Acetolysis of acylated methyl L-ribofuranosides, under sulphuric acid-catalysed conditions, has been investigated in detail using 1 H NMR methods. 20 By comparing the rates of acetolysis of methyl L-ribofuranosides, protected with either benzoyl groups or acetyl groups, in a mixture of acetic acid/acetic anhydride with 0.75% sulphuric acid, both kinetic modelling and the observed formation of methyl hydrogen sulfate allowed protonation of the exocyclic oxygen to be identified as the key process preceding aglycone formation.…”

Larger laboratory scale synthesis of 5-methyluridine and formal synthesis of its L-enantiomer

“…It is obvious that the same sequence of reactions performed on L-glucose will furnish L 5-methyluridine 5. Compound 15 can be directly prepared form D-ribose using HCl-MeOH (→ 13), 5,6 H2SO4-MeOH 7 or AcCl-MeOH 8 followed by benzoylation (→ 14) and acetolysis (→ 15), but since D-glucose is abundant and is one of the cheapest chiral compounds available, we used it to obtain D-ribose and finally 1 at a larger laboratory scale (> 60 g per run) in excellent cumulative yields of ca. 90% for the sequence 15→ 17→ 1.…”