Total Synthesis of (+)-Tubelactomicin A. 1. Stereoselective Synthesis of the Lower-Half Segment by an Intramolecular Diels−Alder Approach

Abstract

[reaction: see text]. Starting from diethyl (R)-malate, synthesis of the lower-half segment of (+)-tubelactomicin A, a 16-membered macrolide antibiotic, has been achieved. The synthesis involved the highly endo- and pi-facial selective intramolecular Diels-Alder reaction achieved using a trisubstituted methacrolein derivative tethering a 10-carbon dienyne unit at the beta-carbon, which in turn was prepared from a known allylated malic acid derivative.

Transition metals in organic synthesis: Highlights for the year 2005

“…Palladium-catalyzed hydrostannations of terminal alkynes, using tributyltin hydride, to give alkenylstannanes were used in total synthesis toward peridinin [35], 6 -epi-peridinin [60], dihydroxerulic and xerulinic acid [38], (+)-tubelactomicin A [64,868] and macrolactin analogs [82]. Regioselective palladium-catalyzed hydrostannations of internal alkynes were used in synthesis toward mycolactones A and B [296], tricyclic core of GKK1032 [81], zoanthamine [83] and xanthocillin X dimethylether [87].…”

Molecular Basis of Elansolid Biosynthesis: Evidence for an Unprecedented Quinone Methide Initiated Intramolecular Diels–Alder Cycloaddition/Macrolactonization

“…Oxidation furnished an aldehyde which was fused with phosphonate 16 by a HWE olefination, and the resulting alkyne 21 was finally desilylated to afford allyl alcohol 22. Phosphonate 16 [16] was prepared from vinyl iodide 15 (from 14 [17] ) which was first elaborated by a Sonogashira-Hagihara alkynylation followed by Appel bromination and Michaelis-Arbusov reaction.…”

Molekulare Grundlage für die Biosynthese von Elansolid: Beweise für eine einzigartige, durch ein Chinonmethid initiierte intramolekulare Diels‐Alder‐Cycloaddition/Makrolactonisierung

“…Durch Oxidation wurde der entspechende Aldehyd erhalten, der mit dem Phosphonat 16 über eine HWE-Olefinierung verbunden wurde. (Das Phosphonat 16 [16] wurde aus dem Vinyliodid 15 (aus 14 [17] ) durch Sonogashira-Hagihara-Alkinylierug, Appel-Bromierung und Michaelis-Arbusov-Reaktion hergestellt.) Das resultierende Alkin 21 wurde schließlich zum Allylalkohol 22 desilyliert.…”