Tertiary Alkaloids of Alstonia spectabilis and Alstonia glabriflora (Apocynaceae)

Abstract

Examination of the tertiary base fraction from Alstonia spectabilis R.Br. has led to the isolation of villalstonine, macralstonidine, vincamajine, quebrachidine, pleiocarpamine, and AT(,)-methylsarpagine. Pleiocarpamine, which is a constituent of Pleiocarpa mutica Benth. and Hunteria eburnea Pichon,l and N(,,-methylsarpagine have been obtained previously as hydrolysis products respectively of the bis-indoles villalstonine and macralstonidine. Drastic conditions are required for the hydrolysis of these bis-indoles, and it is unlikely that a significant amount of hydrolysis would have occurred during the isolation of the alkaloids. N(,)-3Ietliylsarpagine has not previously been isolated directly from natural sources but the quaternary N(b)-metho salt has been isolated from Pleiocarpa mutica.2 The occurrence of vincamajine and of esters of both vincamajine and quebrachidine in Alstonia constricts were recently reported.3 From another Kew Guinea species, Alstonia glabriflora Mgf., the alkaloids villalstonine, macralstonine, pleiocarpamine, and alstophylline have been isolated. Alstophylline, which has been isolated previously as an hydrolysis product of macralstonine and as an alkaloid from Alstonia macrophylla Wall.,4 is one of the major constituents of the tertiary base fraction of A. glabriflora. Experimental (a) Alkaloids from Alstonia spectabilis Bark of Alstonia spectabilis R.Br. (Herbarium voucher number, Hoogland 5138) was collected by Dr R. Hoogland in the southwestern foothills of the Finisterre Mountains in New Guinea. The milled, dried bark (1090 g) was extracted with methanol, and the acidified concentrate diluted with water and defatted by extraction with light petroleum. The concentrate was basified (NH3) and extracted repeatedly with diethyl ether to give 4.8 g tertiary bases. Extraction with chloroform then gave a further 7.0 g tertiary bases. Thn more intractable material extracted by

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

“…This bisindole was isolated from Alstonia macrophylla [22,127,128,129,130], Alstonia angustifolia [131], Alstonia muelleriana [132], and Alstonia glabriflora Mgf. [133]. Several related bisindoles (natural or semi-synthetic) with potent antimalarial activity, (+)- O- methylmacralstonine [22], (+)- O -acetylmacralstonine [40], and (+)-des- N ′ a -methylanhydromacralstonine 97 [73] were also known.…”

“…This alkaloid was originally isolated from Alstonia macrophylla WALL by Kishi, Schmid et al [78,128], from Alstonia glabriflora Mgf. by Hart [133] and from Alstonia angustifolia by Ghedira et al [131]. In addition, the related N a -H analog (+)- N 1 -demethylalstophylline 22a has recently been isolated from Alstonia macrophylla by Kam [43].…”

“…(+)-Macralstonidine 8 represents another dimeric indole alkaloid which consists of a macroline and a sarpagine obligate monomeric unit. It has been isolated from Alstonia macrophylla [127,128], Alstonia somersentenis [127], and Alstonia spectabilis [133]. The alkaloid, N a -methylsarpagine ( 23 ) is a natural product isolated from Alstonia spectabilis by Hart et al [133].…”

“…It has been isolated from Alstonia macrophylla [127,128], Alstonia somersentenis [127], and Alstonia spectabilis [133]. The alkaloid, N a -methylsarpagine ( 23 ) is a natural product isolated from Alstonia spectabilis by Hart et al [133]. Zhao et al reported the first total synthesis of (+)- N a -methylsarpagine, as well as the total synthesis of (+)-macralstonidine, along with several other indole alkaloids [144,145].…”

“…The condensation of (+)-macroline 19 and (+)- N a -methylsarpagine 23 under mildly acidicconditions provided the bisindole alkaloid, (+)-macralstonidine 8 (Scheme 15) [133]. In similar fashion to the case of macralstonine, there are at least two possible mechanisms of the coupling process.…”