Stereocontrolled Synthesis of β-d-Mannuronic Acid Esters:  Synthesis of an Alginate Trisaccharide

Abstract

A facile synthesis route toward beta-linked mannuronic acid oligomers using the corresponding 1-thiomannuronic acid esters in combination with the Ph2SO/Tf2O or NIS/TMSOTf reagent combinations is presented. The presence of the remotely attached carboxylic ester sufficiently influences the electronic environment to allow good to excellent beta-selectivities.

Stereoselective Synthesis of L‐Guluronic Acid Alginates

“…Other promoter systems were investigated to modulate the reactivity of the activated donor species. Iodonium-mediated glycosylations with NIS/trimethylsilyl trifluoromethanesulfonate (TMSOTf) and iodonium dicollidine perchlorate (IDCP) [4,14] resulted in the same stereoselectivity, although the yield did not improve (results not shown). Next, a dehydrative condensation strategy, originally devised by Gin and co-workers, [15] was explored.…”

“…The acetone was removed in vacuo, and the residue was taken up in Et 2 O and washed twice with H 2 O. The organic layer was dried over MgSO 4 and concentrated in vacuo. The residue was dissolved in toluene (2.0 L) and DIBAL-H (137 mL, 1.7 m solution in toluene) was slowly added at 0 8C.…”

“…The reaction was quenched with EtOAc (20 mL) after 20 min, 2 m NaOH (215 mL) was added under vigorous stirring, and the reaction mixture was filtered over Hyflo Gel. The aqueous layer was extracted twice with EtOAc and the combined organic layers dried over MgSO 4 and concentrated in vacuo to afford 2 as a white solid (49 g, 84 %). a,b-l-Gulose (3): Compound 2 (75.5 g, 290 mmol) was added to H 2 O (870 mL) and TFA (174 mL) at 0 8C, after which the reaction mixture was allowed to warm to room temperature.…”

“…The layers were separated and the aqueous phase acidified with 1 m HCl and extracted three times with CH 2 Cl 2 . The combined organic layers were dried over MgSO 4 and concentrated in vacuo. The residue was taken up in DMF (20 mL) and K 2 CO 3 (2.49 g, 18 mmol) and MeI (0.56 mL, 9.0 mmol) was added.…”

“…[4] The present study is focused on the development of a synthetic route to the corresponding 1,2-cis-linked l-guluronic acid oligomers. Analogously to other acidic oligosaccharides, [5] the carboxylate function in l-guluronic acid oligomers can be introduced at the monosaccharide stage by the use of suitably protected lguluronate ester building blocks or at the oligomer level by selective deprotection and oxidation of the incorporated orthogonally protected l-gulose residues.…”