A Substituent‐Directed Strategy for the Selective Synthesis of L‐Hexoses: An Expeditious Route to L‐Idose. Issue 10 (25th February 2021)

• Record Type: Journal Article
• Authors: See, Nicholas W.; Wimmer, Norbert; Krenske, Elizabeth H.; Ferro, Vito
• Is Part Of: European journal of organic chemistry. Issue 10(2021)
• Page Start: 1575
• Page End: 1584
• Publication Date: 2021-02-25
• Subjects: Carbohydrates -- DFT calculations -- Fluorides -- L-sugars -- Radicals; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202100042
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: L‐Hexoses are rare but biologically significant components of various important biomolecules. However, most are prohibitively expensive (if commercially available) which limits their study and biotechnological exploitation. New, efficient methods to access L‐hexoses and their derivatives are thus of great interest. In a previous study, we showcased a stereoselective Bu3 SnH‐mediated transformation of a 5‐ C ‐bromo‐D‐glucuronide to an L‐iduronide. We have now drawn inspiration from this result to derive a new methodology – one that can be harnessed to access other L‐hexoses. DFT calculations demonstrate that a combination of a β‐F at the anomeric position and a methoxycarbonyl substituent at C‐6 is key to optimising the selectivity for the L‐hexose product. Our investigations have also culminated in the development of the shortest known synthetic route to a derivative of L‐idose from a commercially available starting material (45 % yield over 3 steps). Collectively, these results address the profound lack of understanding of how to synthesise L‐hexoses in a stereoselective fashion. Abstract : C‐5 epimerisation via free radical reduction of functionalised D‐hexoses is one of the fastest routes to rare L‐hexoses. With the aid of DFT calculations, we demonstrate that both a β‐F and a C‐6 methoxycarbonyl group installed in a D‐gluco system are key to optimising the stereoselectivity for the L‐ido product. We also present the shortest developed synthetic route to a derivative of L‐idose from a commercially available starting material.