Oxytrofalcatin Puzzle: Total Synthesis and Structural Revision of Oxytrofalcatins B and C

Abstract

The previously reported structures of oxytrofalcatins B and C possess a benzoyl indole core. However, following synthesis and NMR comparison of both the proposed structure and the synthesized oxazole, we have revised the structure of oxytrofalcatins B and C as oxazoles. The synthetic route developed herein can further our understanding of the biosynthetic pathways that govern the production of natural 2,5-diaryloxazoles.

Total Synthesis of the Proposed Structure of Indolyl 1,2-Propanediol Alkaloid, 1-(1H-Indol-3-yloxy)propan-2-ol

“…Large 13 C chemical shift differences were also observed for C2, C3, and C3a positions (Table 2, synthetic 1 (C2): 105.5 ppm vs. reported 1 (C2): 133.6 ppm; synthetic 1 (C3): 119.4 ppm vs. reported 1 (C3): 110.0 ppm; synthetic 1 (C3a): 140.1 ppm vs. reported 1 (C3a): 128.0 ppm). These key discrepancies in 1 H and 13 C NMR data potentially suggested an incorrectly determined indole ring system [6,57]. Unsurprisingly, misinterpretation of 1 H and 13 C NMR data is the most common reason for the misassignment of natural products [58][59][60][61][62][63][64].…”

“…and was published in 2016 by Al-Massarani and co-workers (Figure 1) [49]. Structurally, 1-(1H-Indol-3-yloxy)propan-2-ol (1) differs from previously reported alkoxyindoles [1][2][3][4][5][6][7][8][9]. It has an unprecedented 1,2-propandiol moiety at the C3 position of indole.…”

“…Pyrrolidinoindoline-type alkaloid CPC-1 was isolated from the seeds and rinds of Chimonanthus praecox f. concolor [4]. Oxytrofalcatins A-F and 3-oxygenated N-benzoyl indole analogs from the roots of Oxytropis falcata (Leguminosae) were revised to 2,5-diaryloxazoles by Abe and Yamada [5,6]. Isolated natural products represent a valuable resource of pharmaceutical reagents [7], such as the 5-HT 4 antagonist [8], antiproliferative agents [9], and VATPase inhibitors [10].…”