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

Abstract

A new synthetic route to 1,2‐pyran‐annulated O‐glycosides (pyranopyrans) with β‐manno configuration is presented. Starting from a benzyl‐protected allyl β‐2‐uloside obtained by C2‐oxidation from the corresponding allyl glucoside, vinylation and ring‐closing metathesis provided a bicyclic alkene as a key substrate. Optimized reaction conditions involving the 2‐uloside were required to circumvent the formation of the unwanted 3,2‐enolone. Subsequent stereoselective alkene dihydroxylations were investigated and are presented. Diastereoselective catalytic osmoylation afforded the bicyclic β‐mannoside with syn‐diol configuration. In contrast, a sequence featuring a directed vanadium‐catalyzed alkene epoxidation and epoxide opening provided the corresponding 2,10‐dioxadecalin target compound with trans‐diol configuration. X‐ray crystallography was employed to study the molecular structure of the target compound with syn‐diol configuration. In addition, the molecular packing and hydrogen‐bonding interactions of the hydroxy‐rich molecule were examined.

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

“…The attack of the nucleophile solely occurred from the equatorial side and no diastereomeric byproduct could be detected. Similarly, high stereoselectivities were previously observed for a wide variety of nucleophilic addition reactions to β-2-ulosides [5,[10][11][12]. In order to expand the synthetic applicability of the thus prepared branched mannosides we performed a series of transacetalizations affording products with variably orthogonally protected side chain formyl moieties.…”

“…Previously, Fokt et al [8] described the synthesis of 2 via glycosylation reactions with a 2-ulosyl bromide. However, based on our previously encountered difficulties with comparable glycosylation reactions [5] (i.e., low yields and the formation of side products) we anticipated our approach via Dess-Martin oxidation of 1 to be more efficient. Indeed, 2-uloside 2 was obtained in this way in an excellent 96% yield.…”

“…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. Such C-branched glycosides having an additional aldehyde group were thought to be useful synthetic precursors for 1,2-annulated glycosides.…”

Carbohydrate‐Derived 3,2‐Enolones in the Base‐Catalyzed Rearrangement to Highly Functionalized C4‐Quaternary 4‐Hydroxy‐2‐cyclopentenones

“…As a part of our project on the synthesis of bicyclic carbohydrate derivatives we utilized benzylated β‐2‐ulosides of type 2 , obtained by Dess–Martin oxidation of the corresponding glucosides 1 (Scheme ), as synthetic intermediates. In this context we observed the high tendency of these compounds to form 3,2‐enolones 3 via 3,4‐elimination of benzyl alcohol.…”

“…In this context we observed the high tendency of these compounds to form 3,2‐enolones 3 via 3,4‐elimination of benzyl alcohol. For instance, unbuffered Dess–Martin oxidation of allyl glucoside 1b produced substantial amounts of 3b [1a] as a side product from the acetic acid catalyzed β‐elimination, and even silica‐induced elimination was observed during chromatographic purification of the oxidation product 2b . To examine the applicability of the enolones 3 as carbohydrate building blocks, we investigated conditions for their efficient formation via oxidation and elimination.…”