Biosynthesis of Benzo[c]phenanthridine Alkaloids Sanguinarine, Chelirubine and Macarpine

Abstract

SummaryThe biosynthesis of the benzo [clphenanthridine alkaloids was investigated in a cell suspension culture of Macleaya cordata (papaveraceae). Feeding experiments define the biosynthetic pathway (-)-7,8,13,13 a-tetrahydrocoptisine -+ (-)-cis-Nmethyl-7,8,13,13a-tetrahydrocoptisinium salt 15 + protopine (5) -+ sanguinarine (1) -+ chelirubine (3)+ macarpine (4).Sanguinarine (1) and chelerythrine (2) belong to the benzo [clphenanthridine alkaloids class [I]. These alkaloids occur widely in papaveraceous plants [2]. They have four oxygen functions at the positions 2, 3, 7 and 8. Besides 1 and 2, the alkaloids chelirubine (3), chelirutine, sanguirubine and sanguirutine bearing five oxygen functions at C(2), C(3), C(7), C(8) and C(10) have been isolated from several plants [3]. Macarpine (4) bearing six oxygen functions at C(2), C(3), C(7), C (8), C (10) and C (12) has been also found [4].Although biosynthetic studies on 0,-type alkaloids (sanguinarine and chelerythrine) have been described [5] [6], the biosynthetic route of the 05-and 0,-type alkaloids has been unexplored, presumably due to their poor existence in plants. We now report a biosynthetic investigation on chelirubine (3) and macarpine (4) by using the callus tissues of Macleaya cordata (papaveraceae). Moreover, the opportunity has been taken to investigate in detail the pathway of sanguinarine (1) and chelerythrine (2). A related experiment with the intact plants of Macleaya cordata is also described.The callus tissues of M . cordata were derived from the stem and the root tissue, respectively. Each callus grew to form a mixture of the white and the red-orange colored colonies. The white-type and the red-orange-type colonies were selected visually, and two types of the colonies were subcultured under the same conditions. After subculturing for one year, the alkaloidal fraction of each callus tissue was examined. The alkaloidal components found in our callus tissues always involved the same four alkaloids, sanguinarine (I), chelirubine (3), macarpine (4) and protopine (S), which were also found in the intact plants [7]. Berberine (6), chelerythrine (2) and allocryptopine (7) were not detected in our callus tissues. These results are different from those reported by Neumann et al. [8] or by Furuya et al. 191.

Crystal Structure of (−)‐Corycavinium (+)‐10‐Camphorsulfonate, a biosynthetic intermediate to hexahydrobenzo[c]phenanthridine alkaloids

“…We report here on a biosynthetic investigation of corycavinium (lc) as a key intermediate in the route from protoberberine-type to hexahydrobenzo-[c]phenanthridine-type alkaloids, an investigation using the callus tissues of Corydalis incisa (Papaveraceae). The callus tissues of C. incisa were derived from the stem tissue, and in the suspension cultures the substrates, 13 C-labelled (±)-7V r -methyl-w^ö-tetrahydrocorysaminium (4) chloride and (±)-corycavinium (lc) chloride, were administered according to the previously described procedure [3]. In Table 7, the results of the feeding experiments are listed.…”

“…-Since 1867, there have been chemical studies [1] of protopine-type alkaloids, produced by all papaveraceae spp., with contemporary efforts focussed on this group's biosynthetical behavior [2][3][4][5]. Protopine-type alkaloids function as key intermediates in the metabolism of the protoberberine type (Scheme 1).…”

First Total Synthesis of the Phenolic 7,8-Dihydro-8-oxoprotoberberine Alkaloid, Cerasonine

“…Benzo[c]phenanthridine alkaloids have been biosynthesized from the corresponding protoberberine alkaloids presumably via a 3-arylisoquinoline intermediate. 6) Cerasonine 1, 7) a phenolic protoberberine, was isolated from Polyalthia cerasoides (ROXB.) BEDD.…”

A Concise Synthesis of 8‐Oxoberberine and Oxychelerythrine, Natural Isoquinoline Alkaloids Through Biomimetic Synthetic Way.

“…[17][18][19][20] The synthetic strategy involved in the coupling reaction of Nmethyl-o-toluamide with benzonitrile derivatives. 21 Retrosynthetic analysis of both alkaloids suggested that the coupling reaction of o-toluamide 1 with benzonitrile 2 affords 3-arylisoquinoline 3, which could be converted to 8-oxoberberine 4 via S N 2 type cyclization of amide nitrogen.…”