Occurrence of Indole Alkaloids in Ailanthus altissima Cell Cultures

Abstract

hSTRACT.-~rcduction of alkaloids with both canthin-6-one and P-carboline structure by Adantbur altissima cell cultures is reported. Besides canthin-6-one (l), l-methoxycanthin-6-one (2), canthin-6-one-3-oxide 0, 1-methoxycanthin-6-one-3-oxide (8), l-hydroxycanthin-6-one (3), 5-hydroxycanthin-6-one (6), P-carboline-1-propionic-acid (ll), and 4-methoxy-Pcarboline-I-carboxylic acid methylester (lo), three new alkaloids are described. These are 2-hydroxycanthin-6-one (4), 4-hydroxycanthin-6-one (5), and 4,5-dihydrocanthin-6-one (9).Ailanthus altissima Swingle (Simaroubaceae) is known to be a producer of indole alkaloids and has been extensively studied (1-4). These alkaloids belong to the class of either the simple P-carboline or the more complex canthin-6-one derivatives. The literature has recently reported (5) cell cultures of A. altissima that produced canthin-6-one (1) and 1-methoxycanthin-6-one (2), which are the two most abundant alkaloids in the intact plant.We investigated the production of some minor alkaloids whose presence had been suspected during a previous study undertaken in order to clarify the different steps of their biosynthesis (6). Eleven alkaloids were identified and isolated in satisfactory yields from a batch of 50 liters of cell suspension cultures ofA. altissima. Besides the main alkaloids l and 2, cell cultures produced their corresponding 3-oxides, 7 and 8, respectively, as well as P-carboline-1-propionic acid (ll), 4-methoxy-P-carboline-l-carboxylic acid methylester (lo), 5-hydroxycanthin-6-one (6) previously found in A. altissima (1,2,4), and 1-hydroxycanthin-6-one (3) found in Ailanthus giraldii (7). Furthermore, the following three alkaloids never before found in nature, 2-hydroxycanthin-6-one (4), 4-hydroxycanthin-6-one (5), and 4,5-dihydrocanthin-6-one (9), have been extracted. In spite of the predominant alkaloid canthin-6-one (1) produced in the amount of 300 Fglml of cell suspension, each of the new compounds 4,5, and 9 represent 0.3% of the total alkaloids, and their production is 2 pg/ml or less. RESULTS AND DISCUSSIONIn order to obtain a good amount of crude alkaloids and to identify all the alkaloids present in it, a batch of about 50 liters of cell suspension culture was prepared by pooling 900 Erlenmeyer flask cultures. Cells only were extracted as reported in the Experimental section, the medium being discarded because of its negligible content in alkaloids and high concentration of nutrients. The toluene extract of the cells was loaded on a silica gel column in toluene and eluted with increasing amounts of EtOAc. By this method pure 1 and 2 were obtained, while alkaloids 2,7,8, and 10 required further purification. Compound 9 submitted to eims showed a molecular ion at mlz 222, corresponding to a dihydrocanthin-6-one. The fragmentation pattern was similar to that

Triterpenoids and Sterones from the Stem Bark of Ailanthus altissima

“…As a source plant of quassinoids, A. altissima was also widely investigated. Previous reports revealed the presence of quassinoids, [5][6][7] alkaloids, [8][9][10] and phenolic constituents, 11 and lipids in the plant. 12 As a part of our study on medicinal plants, we investigated the stem bark of this plant, and 14 compounds ( Figure 1) including a new tirucallane-type triterpenoid (1) and a new C 29 sterone (2) were isolated.…”

An Unusual Series of Thiomethylated Canthin‐6‐ones from the North American Mushroom Boletus curtisii

“…The mushroom is obviously able to introduce methylthio residues specifically at the electron deficient C-4, C-5, C-9, and C-11 centers. β-Carboline-1-propanoic acid (9) is the biosynthetic precursor of canthin-6-one (1) in plants, [17] and the occurrence of both compounds in B. curtisii points to the same biosynthetic relationship.…”

Sterones and indole alkaloid from Ailanthus altissima callus cultures

“…However, from the chloroform extract several indole alkaloids could be isolated. Besides canthin-6-one, 1-methoxycanthin-6-one, 1-hydroxycanthin-6-one, canthin-6-one-3-N-oxide, and 4-methoxy-β-carboline-1-carboxylic acid methyl ester, already previously reported as constituents in callus and cell suspension cultures of A. altissima [5,7], 4,8-dimethoxy-β -carboline-1-carboxylic acid methyl ester (3) was found. For 1 H NMR see [20]; 13 C NMR data of 3 are presented here for the first time.…”

“…Its biological activities depend mainly on quassinoids as well as on indole alkaloids, either the simple β-carbolines or the canthin-6-ones [4,5]. Quassinoids from A. altissima have been shown to possess antiplasmodial activity [6,7]. Canthin-6-one alkaloids from A. altissima have proven cytotoxic activity as well as anti-proliferative and antiprotozoal effects [5,8,9].…”