Total Synthesis of Amphidinolide F

Orchestrated yet nonconsonant: The challenge posed by the “umpoled” 1,4-dioxygenation pattern characteristic for the polyketide frame of amphidinolide F was mastered by a late-stage ring-closing alkyne metathesis followed by a directed transannular hydration under the aegis of a carbophilic π-acid catalyst. This concordant strategy enabled a concise total synthesis of this enticing marine natural product

Natural isotope tracers and water filiation in the vine ecosystem

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Concise Total Syntheses of Amphidinolides C and F

The marine natural products amphidinolide C (1) and F (4) differ in their side chains but share a common macrolide core with a signature 1,4-diketone substructure. This particular motif inspired a synthesis plan predicating a late-stage formation of this non-consonant (“umpoled”) pattern by a platinum-catalyzed transannular hydroalkoxylation of a cycloalkyne precursor. This key intermediate was assembled from three building blocks (29, 41 and 47 (or 65)) by Yamaguchi esterification, Stille cross-coupling and a macrocyclization by ring-closing alkyne metathesis (RCAM). This approach illustrates the exquisite alkynophilicity of the catalysts chosen for the RCAM and alkyne hydroalkoxylation steps, which activate triple bonds with remarkable ease but left up to five other π-systems in the respective substrates intact. Interestingly, the inverse chemoselectivity pattern was exploited for the preparation of the tetrahydrofuran building blocks 47 and 65 carrying the different side chains of the two target macrolides. These fragments derive from a common aldehyde precursor 46 formed by an exquisitely alkene-selective cobalt-catalyzed oxidative cyclization of the diunsaturated alcohol 44, which left an adjacent acetylene group untouched. The northern sector 29 was prepared by a two-directional Marshall propargylation strategy, whereas the highly adorned acid subunit 41 derives from D-glutamic acid by an intramolecular oxa-Michael addition and a proline-mediated hydroxyacetone aldol reaction as the key steps; the necessary Me3Sn-group on the terminus of 41 for use in the Stille coupling was installed via enol triflate 39, which was obtained by selective deprotonation/triflation of the ketone site of the precursor 38 without competing enolization of the ester also present in this particular substrate

Natural isotope tracers and water filiation in the vine ecosystem

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Black grain mycetoma caused by Leptosphaeria tompkinsii

International audienceLeptosphaeria tompkinsii is a dematiaceous fungus which is rarely reported as an agent of black-grain mycetoma. We present a case involving a mycetoma of the hand of a former farmer from Mali, West Africa, who has been a resident in France for 27 years. The patient was successfully treated with surgery and the use of oral itraconazole for 6 months. Species identification was based on sexual reproductive structures observed on potato-carrot agar media and the use of internal transcribed spacer sequencing