Synthesis of L‐Altrose and Some Derivatives

Abstract

A convenient approach to the chemical synthesis of L‐altrose (1) and its 6‐deoxy derivative 2 has been developed by starting from D‐galactose (9) and D‐fucose (10), respectively. The 5‐epimerization by a Mitsunobu inversion of the open‐chain D‐hexoses was the key step for these routes. Furthermore, the conversion of 2 into peracetylated TDP‐6‐deoxy‐α‐L‐altrose (3a) was achieved by the cycloSal approach. However, the final deacetylation led to an unexpected side‐reaction resulting in the previously unknown 6‐deoxy‐α‐L‐altropyranose 1,3‐cyclophosphate (4).

Synthesis of l-Hexoses

“…The synthesis started from D-galactose and afforded the corresponding Laltrose. 124 Although Mitsunobu inversion gave moderate to good yield (71%) the installation of the anomeric dithioacetal only gave moderate yield (58%).…”

“…Lunau and Meier also explored C5 epimerization under Mitsunobu conditions of acyclic dithioacetals. The synthesis started from d -galactose and afforded the corresponding l -altrose . Although Mitsunobu inversion gave moderate to good yield (71%) the installation of the anomeric dithioacetal only gave moderate yield (58%).…”

“…Lunau and Meier explored C5 epimerization under Mitsunobu conditions of acyclic dithioacetals. The synthesis started from d -fucose derivative 526 and afforded the corresponding 6-deoxy- l -altrose 530 . Although the crucial Mitsunobu inversion from 527 to 528 gave a good yield (61%), installation of the anomeric dithioacetal ( 527 ) only a gave low yield (28%), thereby limiting the utility of this procedure.…”

One-Pot Domino Aldol Reaction of Indium Enolates Affording 6-Deoxy-α-D,L-altropyranose Derivatives: Synthesis, Mechanism, and Computational Results

“…Herein, we demonstrate that an unusual domino-aldol-aldol-hemiacetal-reaction of group 13 metals, operating best with indium, allows the fabrication of five stereogenic centers in a one-pot reaction thus opening an entry to racemic 6-deoxy altrose derivatives (Scheme ). The temperature dependence of product formation suggests kinetic control at 0–25 °C and thermodynamic bias at 67 °C.…”

Synthesis of All Eight L‐Glycopyranosyl Donors Using CH Activation

“…[11e] Methods of C5 epimeriza-tion include the direct nucleophilic replacement of a leaving group at C5, [12] replacement of a leaving group in constrained pentoses, [13] and the nucleophilic opening of 5,6-anhydropentoses [14a,b] and 4,5-anhydrohexoses. [14c-e] Epimerization at C5 has also been reported to proceed under Mitsunobu conditions, [15] through oxidation/stereoselective reduction, [16] base-catalyzed epimerization of uronic acids, [17] radicalinduced epimerization at C5, [18] and diastereoselective hydroboration of exo-or endocyclic double bonds in unsaturated sugars. [2b, 19] Homologation of sugars with shorter chains has also been reported mainly for the synthesis of l-idose.…”