Calixanthomycin A: Asymmetric Total Synthesis and Structural Determination

Abstract

We report the first asymmetric total synthesis and structural determination of calixanthomycin A. Taking advantage of a modular strategy, a concise approach was developed to assemble the hexacyclic skeleton with both enantiomers of the lactone A ring. Stereoselective glycosylation coupled the angular hexacyclic framework with a monosaccharide fragment to produce calixanthomycin A and its stereoisomers. This enable us to determine and assign the absolute configuration of C-25 (25S) and monosaccharide (derivative of l-glucose).

Selective Axial-to-Equatorial Epimerization of Carbohydrates

“…Due to ultimate cleavage of methyl aglycone, the higher-yielding conditions were carried forward despite the increased formation of the β anomer to access l -quinovose 10 and tri-methyl- l -quinovose 11 in 86 and 88% yields, respectively. Our synthesis of 11 a bioactive rare sugar found in xanthone-type natural product, calixanthomycin Acuts 3 steps from the previous synthesis of 11 , which proceeds from rare l -glucose (> $7,000 per mol) and requires redox manipulation and protecting group interconversions (13% yield overall). , Stereochemistry adjustment, rather than oxidation state adjustment, allows our synthesis to leverage a biomass-derived starting material (< $50 per mol)…”

“…Our synthesis of 11a bioactive rare sugar found in xanthone-type natural product, calixanthomycin Acuts 3 steps from the previous synthesis of 11, which proceeds from rare L-glucose (> $7,000 per mol) and requires redox manipulation and protecting group interconversions (13% yield overall). 40,41 Stereochemistry adjustment, rather than oxidation state adjustment, allows our synthesis to leverage a biomass-derived starting material (< $50 per mol). 41 We hypothesized that the isomerization of 1,6-anhydrosugars, in which a ring flip enforces an axial disposition of substituents that would otherwise be equatorial, could provide access to idose derivatives.…”

Chemistry and biosynthesis of bacterial polycyclic xanthone natural products

“…24). In kigamicins (41)(42)(43)(44)(45), the oxazolidine ring G may arise from the incorporation of an ethanolamine or alanine. In cervinomycins (16)(17)(18)(19)(20)(21)(22)(23)(24)(25), the selectivities on nitrogen donors of aminotransferases may contribute to the molecular diversity of cervinomycins (Fig.…”

Glycosyl Sulfonates Beyond Triflates

“…The authors then used the Ts 2 O‐mediated chemistry to attach this trisaccharide to the aglycone, after more conventional approaches failed to deliver the natural product. More recently, the Gao group used this chemistry with a permethylated quinovose (6‐deoxy glucose) donor in their synthesis of calixanthomycin A [28] …”

“…More recently, the Gao group used this chemistry with a permethylated quinovose (6-deoxy glucose) donor in their synthesis of calixanthomycin A. [28]…”