Abstract
Xestocyclamine A ((−)-1) is featured prominently in a biosynthesis pathway leading to a large family of polycyclic alkaloids. The first total synthesis now proves that the structure of this compound had originally been misassigned. The route to (−)-1 is based on a double Michael addition for the formation of the bridged diazadecalin core and a palladium-catalyzed decarboxylative allylation to install the quaternary bridgehead center. Ring-closing alkyne metathesis allowed a 13-membered cycloalkyne to be forged, which was selectively reduced during an involved sequence of hydroboration/selective protodeborylation/alkyl-Suzuki coupling used to close the 11-membered ring. Crystallographic data prove the identity of synthetic (−)-1 with nominal xestocyclamine, but the spectra differ from those of the authentic alkaloid. To clarify the point, the synthesis was redirected toward ingenamine (3), which is supposedly a positional isomer of 1. The recorded data confirm the assignment of this particular natural product and strongly suggest that xestocyclamine A is in fact the enantiomer of ingenamine (+)-3.
Highlights
Xestocyclamine A ((−)-1) is featured prominently in a biosynthesis pathway leading to a large family of polycyclic alkaloids
A large family of polycyclic alkaloids is thought to derive from macrocyclic dimers such as A as the biosynthetic precursors, which are composed of partly reduced 3alkylpyridine units (Scheme 1).[1]
Since the spectra of the natural products were recorded in different solvents and authentic samples of neither alkaloid were available any longer for reinspection, a total synthesis of ingenamine was necessary to obtain material for comparison
Summary
Since the spectra of the natural products were recorded in different solvents and authentic samples of neither alkaloid were available any longer for reinspection, a total synthesis of ingenamine was necessary to obtain material for comparison. The subsequent RCAM reaction under the conditions described above proceeded smoothly to give cycloalkyne 29 (the structure in the solid state is contained in the SI). Semireduction of this compound with nickel boride[37] was followed by concomitant reduction of the two amides and cleavage of the silyl ether with excess AlH3. The NMR spectra of (−)-3 formed in MeOH-d4 matched those of rigorously acid-free natural ingenamine in the same solvent.[38] Because the spectra in CDCl3/DMSO-d6 were found to be very sensitive to the exact solvent ratio and even trace acid in the medium, any direct comparison is difficult.[39] in the presence of 0.4 equiv of trifluoroacetic acid, the 1H and 13C NMR spectra of synthetic (−)-3 reproduce well those of xestocyclamine A reported in the literature.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
