Two-Step Synthesis of Per-O-acetylfuranoses: Optimization and Rationalization

Abstract

A simple two-step procedure yielding peracetylated furanoses directly from free aldoses was implemented. Key steps of the method are (i) highly selective formation of per-O-(tert-butyldimethylsilyl)furanoses and (ii) their clean conversion into acetyl ones without isomerization. This approach was easily applied to galactose and structurally related carbohydrates such as arabinose, fucose, methyl galacturonate and N-acetylgalactosamine to give the corresponding peracetylated targets. The success of this procedure relied on the control of at least three parameters: (i) the tautomeric equilibrium of the starting unprotected oses, (ii) the steric hindrance of both targeted furanoses and silylating agent, and finally, (iii) the reactivity of each soft nucleophile during the protecting group interconversion.

Synthesis and evaluation of 1,2-trans alkyl galactofuranoside mimetics as mycobacteriostatic agents

“…High Resolution Masses were measured by electrospray with a MS/MS ZabSpec TOF Micromass using m-nitrobenzylic alcohol as a matrix and accelerated caesium ions for ionization (Centre Regional des Mesures Physiques de l'Ouest, Université de 55 Rennes 1). Compounds 8, 27 19, 28 21, 28 26, 29 32, 31 37 32 and 39 33 were prepared according to reported procedures.…”

“…We previously described the formation of the oxazoline derivative of 2-acetamido-2-deoxy-D-galactofuranose (D-GalfNHAc) 30 thanks to the acetylation of per-O-silylated GalfNHAc in presence of acetic anhydride and a large excess of 20 p-toluenesulfonic acid (pTSA). 29 Such oxazoline could nevertheless undergo nucleophilic attack by methanol to give selectively the methyl β-D-GalfNHAc in excellent yield. Unfortunately no reaction occurred when using octanol as nucleophile in presence of various Lewis acids like BF 3 .Et 2 O or 25 TMSOTf.…”

“…The more hydrosoluble and pH-sensitive octyl-D-galactofuranoside uronic acid (octyl D-GalfA) 8 was obtained according to the reported furanosylation strategy of octanol in the presence of calcium chloride. 22 The same procedure was implemented to access the octyl(methyl-β-D-galactofuranosid)uronate 9 using (methyl-β-D-galactopyranoside)uronate 26 29 (Scheme 2). The resulting uronate 9 was obtained as a mixture of anomers with a slight excess towards the β-one.…”

“…Such activated furanoses were easily obtained from the parent sugars as described previously. 29 Glycosylation of octanol by 27, 28 or 29, in the presence of a trifluoroboron etherate complex, generated again the 1,2-trans anomers as the major isomers. They were purified first to remove the 1,2-cis anomer before the subsequent transesterification to give 10, 11 or 12, respectively.…”

“…The reaction mixture was stirred at 50 °C for 2 days. The solvent was evaporated and the residue was CH 2 ),29.4, 29.2, 29.1, 26.0, 22.5 [(CH 2 ) 5 ], 17.4 (CCH 3 ), 13.9 (CH 2 CH 3 ). HRMS (ESI): calcd for C 20 H 34 O 3 Na [M+Na] + 345.2406, found 345.2409.General Procedure for the synthesis of per-O-acetylatedTo a solution of 39 33 (100 mg, 0.23 mmol) in dry DCM (10 mL) were added successively alcohol 32, 34 or 38 (0.31 mmol) and molecular sieves (500 mg).…”