Synthesis of Pyrano‐ and Pyrido‐Anellated Pyranosides as Precursors for Nucleoside Analogues

Abstract

The push‐pull activated methyl (3Z)‐4,6‐O‐benzylidene‐3‐[(methylthio)methylene]‐3‐deoxy‐α‐D‐erythro‐hexopyranosid‐2‐ulose (1) reacted with dialkyl malonate in the presence of potassium carbonate to give the alkyl (2R,4aR,6S,10bS)‐4a,6,8,10b‐tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxylates 2 and 3. Treatment of 1 with 3‐oxo‐N‐phenyl‐butyramide, N‐(4‐methoxy‐phenyl)‐3‐oxo‐butyramide, and 3‐oxo‐N‐o‐tolyl‐butyramide, respectively, in the presence of potassium carbonate and 18‐crown‐6 yielded the (2R,4aR,6S,10bS)‐9‐acetyl‐7‐aryl‐4,4a,7,10b‐tetrahydro‐6‐methoxy‐2‐phenyl[1,3]dioxino‐[4′,5′:5,6]pyrano[3,4‐b]pyridin‐8(6H)‐ones 4–6. (2R,4aR,6S,10bS)‐4,4a,8,10b‐Tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxamide (7) was prepared by anellation reactions of 1 either with malononitrile or with cyanoacetamide.

Keywords:

• Deoxyuloses
• Push‐pull alkenes
• Anellation
• Heterocyclic fused monosaccharides

Acknowledgments

The authors would like to thank the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie for financial support.