A General, Iterative, and Modular Approach toward Carbohydrate Libraries Based on Ruthenium-Catalyzed Oxidative Cyclizations

Abstract

Carbohydrates are an omnipresent class of highly oxygenated natural products. Due to their wide spectra of biological activities, they have been in the center of synthetic organic chemistry for more than 130 years. During the past 50 years non-natural carbohydrates attracted the interest of various chemists in the fields of organic, biological, and medical chemistry. Especially desoxygenated sugars proved to be an important class of compounds. Up to date, most non-natural analogues are synthesized starting from natural, enantiomerically pure carbohydrates in multistep synthesis. In this report, we present a synthetic strategy that allows the selective modular synthesis of natural and non-natural carbohydrates within five synthetic steps starting from readily available starting materials. Due to a sequential introduction of O- or N-functionalities, a regioselective protection of each new functional group is possible. The key step in the carbohydrate synthesis is a RuO4-catalyzed oxidative cyclization via a pH-dependent dehydrogenation-dihydroxylation-cyclization or an oxidative fragmentation-cyclization, leading to highly substituted new carbohydrates, in which each functional group is orthogonally protected and accessible for further synthetic operations.

Indium- and Zinc-Mediated Acyloxyallylation of Protected and Unprotected Aldotetroses—Revealing a Pronounced Diastereodivergence and a Fundamental Difference in the Performance of the Mediating Metal

“…Next, d -threose 14 (the 3-epimer of l -erythrose) and the related protected sugar aldehyde 15 were subjected to the same reaction conditions as indicated above ( 3a , In, EtOH, 45 °C). Compound 15 was prepared via a literature approach 24 with necessary modification of the final oxidation step. 25 Clean and full conversion was again achieved for both starting materials, and the crude reactions mixtures were processed to their fully unprotected enitols 16a – d for quantification as described above ( Scheme 3 , top).…”

“…4- O -Acetyl-2,3 O -isopropylidene- d -threitol 24 (1.00 g, 4.90 mmol, 1.00 equiv) was dissolved in EtOAc (20 mL) in a microwave vial, IBX (4.12 g, 14.7 mmol, 3.00 equiv) was added and atmosphere was changed to argon. The vial was heated in the microwave oven (Biotage Initiator) at 120 °C for 15 min.…”

Preparation of 3-Methylthiodecanal, a Flavour Compound

“…Although ozonolysis is one of the most common methods for the oxidative cleavage of the C=C bond, we chose the Ru-catalysed oxidation reported by Niggemann et al, 27 which was more easily carried out than ozonolysis due to the inconvenient preparation of ozone gas in the laboratory. 4-Benzyloxy-1-undecene 2 was oxidised by 5 mol % of RuCl 3 and 2 equiv.…”

Ruthenium Tetroxide and Perruthenate Chemistry. Recent Advances and Related Transformations Mediated by Other Transition Metal Oxo-species

“…A notable application of the RuO 4 -catalyzed dihydroxylation of alkenes has been reported by Plietker and co-workers [84]. In particular, a synthetic strategy was developed that allowed to obtain a small carbohydrate library based on the pH dependence of three Ru-catalyzed processes: the dehydrogenation of alcohols, the oxidative cleavage of olefins and the dihydroxylation of olefins (Scheme 8, Scheme 9 and Scheme 10).…”