Recent Developments in the Synthesis of 2‐C‐Branched and 1,2‐Annulated Carbohydrates

Abstract

The importance of carbohydrate chemistry in biological and medicinal chemistry has led to enormous developments in the synthesis of carbohydrate mimics. In this context, the synthesis of branched sugars in general and of 2‐C‐branched carbohydrates in particular, as well as the synthesis of 1,2‐annulated sugars, have received immense attention. They serve not only as carbohydrate mimics in the form of stand‐alone molecules, but also as useful intermediates in the synthesis of many natural products, their analogues, and glycosidase inhibitors. This microreview covers the recent synthetic efforts in this area and puts the subject matter into proper perspective for future developments.

2-C-Alkynyl and 2-C-cis-Alkenyl β-Mannosides with Acetal Protected γ-Aldehyde Functionality via 2-Uloside Alkynylation and Lindlar Hydrogenation

“…The molecular structure ( Figure 1) revealed a carbonyl bond length of 1.204 Å (C2-O21) as well as carbonyl angles of 115.3 Å (C1-C2-C3) and 122.3 • (C1-C2-O21 and C3-C2-O21). The carbohydrate system was found to comprise a distorted 4 Our synthetic sequence started by subjecting benzyl β-glucoside 1 [7] to Dess-Martin oxidation to afford the corresponding perbenzylated 2-uloside 2 (Scheme 1). Previously, Fokt et al [8] described the synthesis of 2 via glycosylation reactions with a 2-ulosyl bromide.…”

“…aqueous NaCl solution (25 mL), allowed to warm to ambient temperature, diluted with chloroform (200 mL) and washed with water, satd. aqueous NH 4 Cl solution, satd. aqueous NaHCO 3 solution and water (100 mL each).…”

“…Carbon-branched carbohydrates and especially 1,2-annulated carbohydrates have been the target of considerable synthetic efforts in recent years, for such sugar derivatives may have potential medical application as glycosidase inhibitors [1][2][3][4]. In the context of our current project regarding the development of synthetic strategies towards bicyclic annulated carbohydrate derivatives [5,6], we became interested in the synthesis of 2-C-cis-alkenyl substituted β-mannosides bearing a γ-formyl moiety.…”

1,2‐Annulated Sugars: Synthesis of Polyhydroxylated 2,10‐Dioxadecalins with β‐manno Configuration

“…After 15 min, TLC (toluene/ethyl acetate, 4:1) showed no more progression of the reaction. At -78°C a saturated NH 4 Cl solution (5 mL) was added dropwise, and the reaction mixture was warmed to ambient temperature. The solution was diluted with CH 2 Cl 2 (120 mL) and washed with water (3 × 50 mL).…”

“…Within the structurally rich class of carbon-branched carbohydrates, [1,2] 1,2-annulated carbohydrates have attracted special interest, because they are expected to mimic the transition state in glycosidase-catalyzed reactions. [3][4][5][6][7][8][9][10] Therefore, considerable effort has been invested in the design and the synthesis of such compounds. While bicyclic C-or N-glycosides have been predominantly synthesized in this regard, Ansari et al recently described the synthesis and enzymatic inhibitory evaluation of an O-glycosidic 2,10-dioxadecalin system A ( Figure 1) featuring an α-D-galacto-configured parent carbohydrate moiety.…”