Perhentidines A–C: Macroline–Macroline Bisindoles from Alstonia and the Absolute Configuration of Perhentinine and Macralstonine

Abstract

Three new bisindole alkaloids of the macroline-macroline type, perhentidines A-C (1-3), were isolated from the stem-bark extract of Alstonia macrophylla and Alstonia angustifolia. The structures of these alkaloids were established on the basis of NMR and MS analyses. The absolute configurations of perhentinine (4) and macralstonine (5) were established by X-ray diffraction analyses, which facilitated assignment of the configuration at C-20 in the regioisomeric bisindole alkaloids perhentidines A-C (1-3). A potentially useful method for the determination of the configuration at C-20 based on comparison of the NMR chemical shifts of the bisindoles and their acetate derivatives, in these and related bisindoles with similar constitution and branching of the monomeric units, is also presented.

Synthesis of Bisindole Alkaloids from the Apocynaceae Which Contain a Macroline or Sarpagine Unit: A Review

“…Fortunately, it was possible to trap the acyclic form as the O- acetyl derivative 9b (Figure 7) which clearly indicated the C-20 to be in R ( β -H) configuration after spectroscopic analysis. This was further confirmed by X-ray analysis of (+)-macralstonine which was crystallized as the hemiketal 9 [129].…”

“…(+)-Macralstonine 9 is a dimeric alkaloid which consists of two macroline cores which belong to the Alstonia alkaloids (−)-alstophylline 22 and (+)-macroline 19 . This bisindole was isolated from Alstonia macrophylla [22,127,128,129,130], Alstonia angustifolia [131], Alstonia muelleriana [132], and Alstonia glabriflora Mgf. [133].…”

“…In their NMR (NOESY) spectroscopic studies of the O- methyl congener 11 during its isolation from A. macrophylla [22,130], Keawpradub et al and Changwichit et al concluded the stereochemistry at C-20 to be R ( β -H). In the case of macralstonine [129], NOESY was not feasible. Fortunately, it was possible to trap the acyclic form as the O- acetyl derivative 9b (Figure 7) which clearly indicated the C-20 to be in R ( β -H) configuration after spectroscopic analysis.…”

Monoterpenoid Indole Alkaloids from Alstonia rupestris with Cytotoxic, Anti-Inflammatory and Antifungal Activities

“…Several of these species are used in Traditional Chinese Medicine, for example in the treatment of malaria, dysentery, defervescence, antitussive, and to arrest hemorrhages [5,6,7,8,9,10]. Monoterpenoid indole alkaloids occur abundantly in the family Apocynaceae [11,12,13,14,15,16,17], and to date, more than 300 such monoterpenoid indole alkaloids have been reported from the plants of this genus [18,19,20,21,22]. This type of alkaloids originates from the condensation of tryptophan with secologanin to give strictosidine and then further elaboration gives an impressive array of structural variants [23].…”

Monoterpenoid Indole Alkaloids from Alstonia yunnanensis and Their Cytotoxic and Anti-inflammatory Activities

“…Several of these species are used in Traditional Medicine, for example in the treatment of malaria, dysentery, defervescence, antitussive, and to arrest hemorrhages [ 5 , 6 , 7 , 8 , 9 , 10 ]. Plants belonging to this genus represent a rich source of biologically-active unique heterocyclic alkaloids having a monoterpene indole skeleton [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Monoterpenoid indole alkaloids originate from the condensation of tryptophan with secologanin to give strictosidine and subsequent elaboration to give an impressive array of structural variants [ 26 ].…”