Acyl Glycosides through Stereospecific Glycosyl Cross-Coupling: Rapid Access to C(sp³)-Linked Glycomimetics

Abstract

Replacement of a glycosidic bond with hydrolytically stable C–C surrogates is an efficient strategy to access glycomimetics with improved physicochemical and pharmacological properties. We describe here a stereoretentive cross-coupling reaction of glycosyl stannanes with C(sp2)- and C(sp3)-thio(seleno)esters suitable for the preparation C-acyl glycosides as synthetic building blocks to obtain C(sp3)-linked and fluorinated glycomimetics. First, we identified a set of standardized conditions employing a Pd(0) precatalyst, CuCl additive, and phosphite ligand that provided access to C-acyl glycosides without deterioration of anomeric integrity and decarbonylation of the acyl donors (>40 examples). Second, we demonstrated that C(sp3)-glycomimetics could be introduced into the anomeric position via a direct conversion of C1 ketones. Specifically, the conversion of the carbonyl group into a CF2 mimetic is an appealing method to access valuable fluorinated analogues. We also illustrate that the introduction of other carbonyl-based groups into the C1 position of mono- and oligosaccharides can be accomplished using the corresponding acyl donors. This protocol is amenable to late-stage glycodiversification and programmed mutation of the C–O bond into hydrolytically stable C–C bonds. Taken together, stereoretentive anomeric acylation represents a convenient method to prepare a diverse set of glycan mimetics with minimal synthetic manipulations and with absolute control of anomeric configuration.

Acyl and Benzyl‐C‐β‐D‐Glucosides: Synthesis and Biostudies for Glucose‐Uptake‐Promoting Activity in C2C12 Mytotubes

“…R f = 0.4 (EtOAc/hexanes, 1:4); m.p = 75-77°C; [α] 25 D =6.1 (c 0.5, CHCl 3 ); All spectroscopic data for our synthetic molecule ( 1 H, 13 C, HRMS) were well in agreement with those reported for the same. [15] 2, 4,5, 2, 4,5,4,…”

“…1-bromo-3,4,5-trichlorobenzene (1.28 g, 4.9 mmol) in anhydrous THF was added into the activated magnesium. [15] 2, 4,5,phenyl)-aldehydo-D-glycero-D-gulo-heptose (12j): Building block 6c (0.5 g, 1.13 mmol) in anhydrous THF was added to reaction mixture.…”

“…[9] No synthetic route is available based on disconnection III, through utilization of synthon C. Disconnection IV envisaging use of synthon D seems to be the most attractive, as it demands mere addition of ArMgX onto C- 1-functionalized D-glucose building blocks such as 6a or 6b. [15] Although cross-coupling reactions, such as these are emerging for the said objectives, the use of expensive transition metal catalyst and scaling up of the reactions are the associated limitations. [10] Similarly, the use of 1-formyl-α-C-glucoside has been made in an attempt to access the corresponding 1-acyl-α-C-glucosides.…”

Design and synthesis of glycomimetics: Recent advances

“…Another method recently introduced by Zhu et al employed a stereoretentive palladium‐catalyzed acylation reaction of anomeric stannanes 126 and 127 (Figure ) with thio‐ and selenoesters, affording the corresponding C ‐acyl glycosides 128 and 129 with retention of configuration. Anomeric stannanes are configurationally stable nucleophiles that can be stored and manipulated under ambient conditions without loss of stereochemical integrity, even after extended periods of time (6 months at room temperature or 1 year at −20°C).…”

β‐Selektive C‐Glycosylierung und ihre Anwendung in der Synthese von Scleropentasid A

“…[11] Jüngst wurde durch Walczak et al auch eine Kreuzkupplung von Glycosylstannanen 7 unter Verwendung überstçchiometrischer Mengen von Kupfersalzen beschrieben. [12] Unser Ansatz bedient sich einer schwermetallfreien Umpolungsreaktion zur C-C-Bindungsknüpfung am anomeren Zentrum. Die retrosynthetische Analyse von Scleropentasid A( 1)e rfordert d-Glucose 9 und Furfural 10 als Ausgangsverbindungen (Schema 3).…”