Organocatalytic Synthesis of Higher-Carbon Sugars: Efficient Protocol for the Synthesis of Natural Sedoheptulose and d-Glycero-l-galacto-oct-2-ulose

Abstract

Herein we report a short and efficient protocol for the synthesis of naturally occurring higher-carbon sugars-sedoheptulose (d-altro-hept-2-ulose) and d-glycero-l-galacto-oct-2-ulose-from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn-selective aldol reaction of DHA with d-erythrose and d-xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn-selective carbon-carbon-bond-forming aldol reactions promoted by primary-based organocatalysts. For example, this methodology provided useful access to d-glycero-d-galacto-oct-2-ulose and 1-deoxy-d-glycero-d-galacto-oct-2-ulose from d-arabinose in high yield (85 and 74 %, respectively) and high stereoselectivity (99:1).

Keywords: aldol reaction; asymmetric synthesis; carbohydrates; natural products; organocatalysis.

Scheme 1

Natural higher‐carbon heptose and octose.

Scheme 2

Retrosynthetic analysis of hept‐2‐ulose and oct‐2‐ulose.

Scheme 3

Stereoselective synthesis of sedoheptulose. Reagents and conditions: a) BnBr, NaH, imidazole, Bu₄NI, DMF, 0 °C, 2 h, 79 %; b) Amberlyst 15 hydrogen form, MeOH, RT, 24 h, 82 %; c) H₂, Pd/C, MeOH, RT, 20 h, 98 %. Overall yield: 63 %.

Scheme 4

Stereoselective synthesis of d‐glycero‐l‐galacto‐oct‐2‐ulose.

Scheme 5

Stereoselective synthesis of d‐glycero‐d‐galacto‐oct‐2‐ulose and 1‐deoxy‐d‐glycero‐d‐galacto‐oct‐2‐ulose.