Total Synthesis, Stereochemical Assignment, and Biological Activity of All Known (−)-Trigonoliimines

Abstract

A full account of our concise and enantioselective total syntheses of all known (−)-trigonoliimine alkaloids is described. Our retrobiosynthetic analysis of these natural products enabled identification of a single bistryptamine precursor as a precursor to all known trigonoliimines through a sequence of transformations involving asymmetric oxidation and reorganization. Our enantioselective syntheses of these alkaloids enabled the revision of the absolute stereochemistry of (−)-trigonoliimines A, B, and C. We report that trigonoliimines A, B, C, and structurally related compounds showed weak anticancer activities against HeLa and U-937 cells.

Bioinspired Total Synthesis of Sespenine

“…In the presence of AcOH (2.0 equiv), exposure of 20 to OsO 4 /NMO also provided 24 , albeit in low yield (entry 4). We then examined the oxaziridine 25 ,23 which was successfully used for the indole C3 hydroxylation 13e–i. Similarly, mildly acidic conditions were required for generating 24 (10 % yield, entry 5).…”

Recent studies on the chemical constituents of Trigonostemon plants

“…3) have been isolated from the plants of T. thyrsoideum, T. heterophyllus, T. howii, T. chinensis, T. cherrieri, and T. xyphophylloides. For the most of these daphnane diterpenoids, the H-10 was α-configured, but trigoxyphins H (62) and I (53) were the exceptions, where the H-10 was β-directed. ), 15 F (52), 15 H (62), 19 I (53), 19 and K (61) 20 possessed the same 9,13,14-orthobenzoate moiety at the six-membered C-ring, while the rest of the 14 analogues, namely trigothysoids A-E (42-44, 36-39, resp.…”

Organocatalytic Enantioselective Aza‐Friedel–Crafts Reaction of Cyclic Ketimines with Pyrroles using Imidazolinephosphoric Acid Catalysts

“…Chiral indoline‐3‐ones with a quaternary chiral carbon center at the 2‐position are an important class of synthetic targets, because they are often found in a broad range of biologically active compounds, such as (−)‐trigonoliimine C, (+)‐isatisine A, (−)‐brevianamide B, (+)‐aristotelone, (+)‐austamide, and other natural compounds (Figure ) . Although many synthetic strategies towards chiral indoline‐3‐ones have been reported, only a few examples of the catalytic asymmetric synthesis of optically active indoline‐3‐ones with a quaternary carbon center can be found in literature .…”

“…The chiral catalysts can be recovered by as ingle separation step using columnc hromatography and are reusable without further purification.B ased on the experimental investigations,apossible transition state has been proposed to explain the origin of the asymmetricinduction. Chiral indoline-3-ones with aq uaternary chiral carbon center at the 2-position are an important class of synthetic targets, because they are often found in ab road range of biologically active compounds, such as (À)-trigonoliimineC , [1] (+ +)-isatisine A, [2] (À)-brevianamide B, [3] (+ +)-aristotelone, [4] (+ +)-austamide, [5] and other natural compounds ( Figure 1). [6] Although many synthetic strategies towards chiral indoline-3-ones have been reported, [7] only af ew examples of the catalytic asymmetric synthesis of optically active indoline-3-ones with aq uaternary carbon center can be found in literature.…”