Bipleiophylline, an Unprecedented Cytotoxic Bisindole Alkaloid Constituted from the Bridging of Two Indole Moieties by an Aromatic Spacer Unit

Abstract

A cytotoxic bisindole alkaloid possessing an unprecedented structure in which two indole moieties are bridged by an aromatic spacer unit has been isolated from Alstonia angustifolia. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway from pyrocatechuic acid and pleiocarpamine is presented.

Unusual indole alkaloid–pyrrole, –pyrone, and –carbamic acid adducts from Alstonia angustifolia

“…In the case of pleiomaltinine (5), the sequence is initiated by a lone-pair assisted conjugate addition of 14 through its nucleophilic C-7 onto the oxidized, conjugated, 1,2-diketone form (15) of the naturally-occurring hydroxypyrone, maltol. This is then followed by intramolecular capture of the resultant iminium ion by the enol OH to give 5.…”

“…21 We previously reported the structure of the novel Alstonia alkaloid, bipleiophylline, a cytotoxic bisindole constituted from the bridging of two indole moieties by an aromatic spacer unit. 15 In continuation of our studies of biologically active alkaloids from Malaysian Alstonia 5e10, 15 we wish to report the structure of three unusual alkaloids, viz., an alkaloidepyrrole, an alkaloidepyrone, and an alkaloidecarbamic acid adduct from the stem-bark extract of the Malayan A. angustifolia Wall.…”

Direct Oxidative Coupling of N‐Acetyl Indoles and Phenols for the Synthesis of Benzofuroindolines Related to Phalarine

“…2 The union of phenol 1 and indole 2 under oxidative conditions could lead to two regioisomeric adducts: the hemiaminal containing benzofuro[2,3‐ b ]indoline 3 or the 1‐phenoxy‐2‐aniline‐ethane containing benzofuro[3,2‐ b ]indoline 4 (Scheme ). Benzofuroindoline frameworks of type 3 are found in the diazonamides,1a,b azonazine,1c bipleiophylline,1d voacalgine A,1e pleiocraline, and pleiocorine 1f–h. In contrast, phalarine is the only natural product that displays a benzofuroindoline skeleton of type 4 2…”

Pardon the Interruption: A Modification of Fischer’s Venerable ­Reaction for the Synthesis of Heterocycles and Natural Products

“…Around the same time, arguably more ‘exotic’ natural products such as diazonamide A ( 5 ) 9 and communesin B ( 6 ) 10 were also ‘hot targets’. Finally, natural products like aspidodasycarpine ( 7 ) 11 and bipleiophylline ( 8 ) 12 appeared in isolation reports around the time I began my academic career. Although all of these natural products were not bio-synthetically related, their structures uniformly showcased a fused indoline-motif with a C3 quaternary stereocenter (e.g., 1 ), albeit with varying degrees of decoration.…”