A total synthesis of the sesquiterpene lactone aquatolide has been accomplished. The central step is an intramolecular [2 + 2]-photocycloaddition of an allene onto an α,β-unsaturated δ-lactone. Other key steps are an intramolecular Horner-Wadsworth-Emmons reaction to close the lactone and an intramolecular Mukaiyama-type aldol reaction to cyclize the eight-membered ring. Racemic aquatolide has been resolved using preparative HPLC.
Monoterpenoid indole alkaloids are the major class of tryptamine‐derived alkaloids found in nature. Together with their structural complexity, this has attracted great interest from synthetic organic chemists. In this Review, the syntheses of Aspidosperma and Strychnos alkaloids through dearomatization of indoles are discussed.
The revision of the structure of
the sesquiterpene aquatolide from
a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling
NMR data, X-ray crystallography, and the recent confirmation via full
synthesis exemplify that the achievement of “structural correctness”
depends on the completeness of the experimental evidence. Archived
FIDs and newly acquired aquatolide spectra demonstrate that archiving
and rigorous interpretation of 1D 1H NMR data may enhance
the reproducibility of (bio)chemical research and curb the growing
trend of structural misassignments. Despite being the most accessible
NMR experiment, 1D 1H spectra encode a wealth of information
about bonds and molecular geometry that may be fully mined by 1H iterative full spin analysis (HiFSA). Fully characterized
1D 1H spectra are unideterminant for a given structure.
The corresponding FIDs may be readily submitted with publications
and collected in databases. Proton NMR spectra are indispensable for
structural characterization even in conjunction with 2D data. Quantum
interaction and linkage tables (QuILTs) are introduced for a more
intuitive visualization of 1D J-coupling relationships,
NOESY correlations, and heteronuclear experiments. Overall, this study
represents a significant contribution to best practices in NMR-based
structural analysis and dereplication.
The N-iodosuccinimide-mediated spirocyclization of tryptamine-derived isocyanides to generate spiroindolenines is reported. The products contain both an imine and an imidoyl iodide as flexible handles for follow-up chemistry.N ucleophilic addition typically occurs chemoselectively on the imine moiety with complete diastereoselectivity,p roviding opportunities for the construction of complex molecular frameworks. The synthetic potential of the method was showcased in the formal total synthesis of (AE)-aspidofractinine.
We report a highly diastereoselective interrupted Ugi reaction to construct a broad range of structurally congested and stereochemically complex spiroindolines from tryptamine-derived isocyanides. The reaction is facilitated by using fluorinated alcohols (TFE or HFIP) as solvents and tolerates a broad range of amines, aldehydes and 2-isocyanoethylindoles to give polycyclic products in moderate to excellent yields.
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