The Naturally Occurring Ketene Acetal Benesudon: Total Synthesis and Assignment of Relative and Absolute Stereochemistry

Abstract

The densely functionalized ketene acetal benesudon, which is a bioactive fungal metabolite, was synthesized from D-glucose by a route involving radical cyclization to form the five-membered ring, and oxidative decarboxylation to generate the key central double bond. The originally suggested stereochemistry for the quaternary center C(5) must be revised, as both C(5) epimers were prepared and a comparison with an authentic sample was made. The absolute configuration of benesudon is 4S,5R,6S.

Enantioselective Total Synthesis of the Morphogen (−)‐Thallusin and Mediated Uptake of Fe(III) into the Green Seaweed Ulva

“…An attempt of enol ether αcyanation by halogenation, substitution with cyanide, and elimination, failed. [39,40] However, direct electrophilic cyanation to nitrile 22 using ICN generated in situ [41] was successful (81 % yield), and iodination provided the substrate 23. Unfortunately, sp 2 -sp 2 -coupling and borylation attempts remained unsuccessful again for iodide 23.…”

“…To possibly reduce strain, lactone 3 was reduced to the corresponding lactol, which yielded dihydropyran 21 after elimination (Scheme 7, path B). An attempt of enol ether α ‐cyanation by halogenation, substitution with cyanide, and elimination, failed [39,40] . However, direct electrophilic cyanation to nitrile 22 using ICN generated in situ [41] was successful (81 % yield), and iodination provided the substrate 23 .…”

Synthesis of Highly Functionalised Furo[3,4-b]pyrans: Towards the Fungal Metabolite (−)-TAN-2483B

“…Benesudon has a ketene acetal function embedded in the bicyclic ring system, and was isolated from a terrestrial fungus. [90] Clive et al utilised the V-H formylation of functionalised galactal 279 as one of the key steps in their initial attempt to synthesise the enantiomer of naturally occurring benesudon (Scheme 3.3). [90] Alcohol 281 was revealed by exposure of aldehyde 280 to in situ generated MeOCH 2 OCH 2 Li.…”

“…[90] Clive et al utilised the V-H formylation of functionalised galactal 279 as one of the key steps in their initial attempt to synthesise the enantiomer of naturally occurring benesudon (Scheme 3.3). [90] Alcohol 281 was revealed by exposure of aldehyde 280 to in situ generated MeOCH 2 OCH 2 Li. Formation of the bicyclic framework of ent-benesudon was accomplished by bromination of the enol ether double bond in 282 with concomitant cleavage of the MOM group, followed by cyclisation to afford furo[2,3-b]pyran 283.…”

“…Reported V-H formylation in synthesis of main bicyclic carbon skeleton of natural product ent-benesudon [90] The major challenge of the dichlorocyclopropane route was the difficulty in functionalisation of the alkenyl chloride functionality to form a carboxyl group. This problem might be circumvented by the use of the 2-C-formyl glycal moiety as one of the key intermediates.…”