Total Synthesis and Structural Revision of the Alkaloid Incargranine B

Abstract

Seeing double: Consideration of the biosynthetic origins of incargranine B, which was originally assigned an unprecedented indolo[1.7]naphthyridine structure, led to the proposal of a dipyrroloquinoline framework as a more biosynthetically feasible structure (see scheme; Piv=pivaloyl). This hypothesis was validated by a short biomimetic synthesis of incargranine B.

The importance of asking “how and why?” in natural product structure elucidation

“…3). 16 We proposed phenylethanoid-diamine 11 represented a reasonable biosynthetic precursor to incargranine B (Scheme 2b). Oxidative deamination of diamine 11 could give an aldehyde 12, which, following intramolecular condensation, would give an N-aryl enamine 13.…”

“…16 The acetal protected cyclisation precursor 15 (prepared in 3 steps) was exposed to 2 M aqueous HCl to deprotect the aldehyde and induce the condensation/Mannich/S E Ar reaction sequence, giving a mixture of two dimeric products 16 and 17, in 50% isolated yield. Analysis of the 1 H and 13 C NMR spectra for the minor product, 17, revealed key similarities with the NMR data reported for incargranine B.…”

Structural Revision and Biomimetic Synthesis of Goupiolone B

“…These results indicated that the biosynthetic consideration combined with the theoretical calculation of NMR data is helpful to accurately elucidate the complicated structure of natural products. [20] …”

Total Synthesis of Ramonanins A–D

“…There are no reports of 1,2-dimethylenecyclopentane-type structures undergoing Diels-Alder dimerizations under ambient conditions. [13] The synthesis began with the high yielding conversion of vanillin into its benzene sulfonate ester, a process that could be easily conducted on large scale (Scheme 2). b) Schroeder's proposed biosynthesis of the ramonanins A-D (3-6).…”

“…[12] To investigate the nature of this fascinating biosynthetic dimerization we chose to pursue a total synthesis of the ramonanin natural products (3)(4)(5)(6). [13] The synthesis began with the high yielding conversion of vanillin into its benzene sulfonate ester, a process that could be easily conducted on large scale (Scheme 2). Two molecules of the resulting aldehyde 8 were united through an acetylene unit in a one-pot sequence to afford multigram quantities of diacetate 9 as a 1:1 mixture of diastereomers.…”