The Total Synthesis of C-Glycosides with Completely Resolved Seven-Carbon Backbone Polyol Stereochemistry: Stereochemical Correlations and Access toL-Configured and Other Rare Carbohydrates

Abstract

The de novo synthesis of a full set of hydroxymethyl C-glycosides from only two precursors is described. The seven-carbon target molecules contain five stereocentres and bridge the stereochemical gap between natural D-configured and non-natural L-configured series of hexoses. Key steps include hydroxylation, differential protection, stereoselective reduction and desymmetrization of 8-oxabicyclo[3.2.1]oct-6-enes. C-Terminus differentiation and C-terminus excision of the seven-carbon polyol backbone lead to hexoses, including those of the L-series. A stereochemical and genetic classification of C-glycosides is presented.

(1R,2R,3R,4S,5S)-3-Methyl-8-oxabicyclo[3.2.1]oct-6-ene-2,4-diyl diacetate

“…Several 8-oxabicyclo[3.2.1] octane derivatives possess moderate anti-HIV activity, see: Montana et al (2009). For the syntheses of a full set of hybrid d-and l-C-glycosides and thymine polyoxin C starting with the unsaturated 8oxabicyclo[3.2.1]octane framework, see: Gethin & Simpkins (1997); Hoffmann et al (2001). For the synthesis of an 8oxabicyclo[3.2.1]octane from tetrachlorocyclopropene and furan, see: Batson et al (2004).…”

“…For a synthetic approach to 8oxabicyclo[3.2.1]octane derivatives based on the reaction of tetrachlorocyclopropene with furan, see: Law & Tobey (1968). For structures of related 8-oxabicyclo[3.2.1]octanes, see: Kreiselmeier et al (2006); Hoffmann et al (2001). For a report of prior research, see: Tafeenko et al (2009).…”

Preparation and Synthetic Applications of 8-Oxabicyclo[3.2.1]oct-6-en-3-one Derivatives

“…Other routes toward a wide variety of sugars were proposed by Vo gel and coworkers [11] starting from Diels-Alder adducts of furan. The 8-oxabicyclo[3.2.1] oct-6-en-3-one provided another synthon of choice and was exploited by Hoffmann et al [12] to generate a set of C-glycosides presenting diverse configurations on the backbone. For that purpose, an asymmetric version of the dipolar [3+4] cycloaddition [13] was developed (Scheme 3).…”

8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐one: Anwendungen in der asymmetrischen Synthese polyoxygenierter Bausteine

“…Im Unterschied dazu lieferte die direkte Oxidation des Silylenolethers 65 mit DMDO das entsprechende α‐Hydroxyketon mit einer axialen Hydroxygruppe. Einfacher und sauberer gelang die Oxidation zum axialen α‐Hydroxyketon mit mCPBA in wasserhaltigem THF 54. Weitere Transformationen, die die Bandbreite dieser Methode unterstreichen, umfassen die oxidative Spaltung des α‐Hydroxyketons ( 67 → 68 ) und das Öffnen der Etherbrücke ( 66 → 69 ) 51.…”

“…Die Desymmetrisierung von meso ‐konfigurierten [4+3]‐Cycloaddukten durch asymmetrische Deprotonierung und die asymmetrische [4+3]‐Cycloaddition wurde in unserer Arbeitsgruppe zur De‐novo‐Synthese eines Satzes aus sieben C‐Glycosiden mit diverser und voll aufgelöster Stereochemie des C 7 ‐Rückgrats verwendet (Schema ) 54. Zur Einstellung des Oxygenierungsmusters wurde entweder eine stufenweise α,α′‐Dioxygenierung der meso ‐konfigurierten Ausgangsverbindung ( meso ‐ 54 → 75 ) oder eine regioselektive α‐Oxygenierung des enantiomerenreinen Cycloaddukts ( 16 → 80 ) durchgeführt.…”