Ru-Catalyzed Isomerization of Achmatowicz Derivatives: A Sustainable Route to Biorenewables and Bioactive Lactones

Abstract

A Ru-catalyzed isomerization of Achmatowicz derivatives that opens unexplored routes to diversify the biogenic furanic platform is reported. The mechanistic insights of this formally redox-neutral intramolecular process were studied computationally and by deuterium labeling. The transformation proved to be a robust synthetic tool to achieve the synthesis of bioderived-monomers and a series of 4-keto-δ-valerolactones that further enabled the development of a flexible strategy for the synthesis of acetogenins. A concise and protective group-free asymmetric total synthesis of two natural products, namely, (S,S)muricatacin and the (S,S)-L-factor, is also described.

Cu‐Catalyzed Tandem Oxidation‐Intramolecular Cannizzaro Reaction of Biorenewables and Bioactive Molecules

“…Unless otherwise noted, all chemicals were purchased from commercial sources and were used without further purification. The KVL was obtained in 84 % according to previously reported procedure [26] . With the exception of [Cu(py) 4 ]PF 6 all the used in this study Cu‐catalysts were obtained from Sigma Aldrich and TCI.…”

“…The KVL was obtained in 84 % according to previously reported procedure. [26] With the exception of [Cu(py) 4 ]PF 6 all the used in this study Cu-catalysts were obtained from Sigma Aldrich and TCI.…”

“…Recently, we reported a Ru‐catalyzed isomerization of Achmatowicz derivatives that results in the formation of 4‐keto‐δ‐valerolactones [26] . In particular, the Achmatowicz product derived from the biorenewable furfuryl alcohol was converted in high yields to dihydro‐2H‐pyran‐2,5(6H)‐dione ( KVL ).…”

“…Recently, we reported a Ru-catalyzed isomerization of Achmatowicz derivatives that results in the formation of 4-ketoδ-valerolactones. [26] In particular, the Achmatowicz product derived from the biorenewable furfuryl alcohol was converted in high yields to dihydro-2H-pyran-2,5(6H)-dione (KVL). Therefore, we foresee the hydroxy ketone moiety in its corresponding methyl ester 1 (Scheme 1) as an excellent starting material to achieve the synthesis of esters of α-hydroxyglutaric acid, which is an oncometabolite [27][28][29][30] and potential cardioprotective agent.…”

Application of Redox-Active Ester Catalysis to the Synthesis of Pyranose Alkyl C-Glycosides

“…Extensive reaction optimization identified the substituted PyBox derivative L4 as the ideal ligand to enable consistent couplings with 5a and 5b . Our coupling conditions were also scalable for the production of C -glycosides bearing α-alkoxy furans, which could in turn function as handles for accessing a variety of biologically significant structures. − Further elaboration of C -glycosides 17β and 17α to methylene-linked pseudodisaccharides was made possible by a de novo sequence featuring an Achmatowicz rearrangement and stereoselective oxidation/reductions. Acetonide protection of C-linked disaccharides 22β and 22α , coupled with 1 H NOE and 2D NMR experiments, enabled full characterization of our final disaccharides as containing a d -mannose sugar at the reducing end, in agreement with the literature precedent (see the Supporting Information).…”