Phenanthridine-type alkaloids

The alkaloid contents in a single alkaloid cell from M. cordata roots of three different thicknesses (age 1-2 years) were determined as follows. The liquid from various numbers of alkaloid cells (Table II) was removed uniformly and collected in the microtrap. The liquid in the capillary and connection tubes was washed into the microtrap to make a certain definite volume for analysis. Quantitative analysis of each alkaloid was carried by preparing a calibration graph (4). Figure 3 shows the HPLC chromatogram of alkaloids from the alkaloid cells. The content of each alkaloid per single alkaloid cell in tissues from three different thickness of roots and its ratio are shown in Table II. The liquid in colorless cells contained only a minute amount of protopine and allocryptopine (Fig. 3). The thicker the roots, the more alkaloids were contained in a single alkaloid cell. In any thickness of root, the content of protopine-type alkaloids exceeded that of benzo[c]phenanthridine-type alkaloids. The ratio of the former to the latter was almost steady over 5 mm of root thickness (86-87%). The ratio of alkaloids in methanol extracts of the same fresh samples (thickness 5 mm) was determined by HPLC (Table III). The ratio of protopine-type alkaloids in the methanol extracts ( 80%) was less than that in the liquid from the alkaloid cells ( 87%). This was because the liquid in alkaloid cells near the cambium were picked up more than that in center cells (pith). Thus, intracellular components scattered in different places are analyzed qualitatively and quantitatively in situ by HC. 

In 1991, Ayer et al. reported on the isolation and structure elucidation of a second phenanthridine type alkaloid antibiotic called jadomycin (118), which is a product of the culture of S. venezuelae ISP5230 when the medium is fed with galactose and the temperature is raised to 37°C. When the medium contains glucose-isoleucine at 28°C, the product is chloramphenicol (120) (47). The filtrate of the culture broth was acidified with 6 M HCl and extracted with EtOAc. After evaporation of the solvent, the product was subjected to a reverse-phase flash column chromatography, which was first washed with H2O and then eluted with a MeOH/H20 step gradient. The fraction eluted with 90% MeOH gave jadomycin, which was further purified by reverse-phase HPLC. 

The Skeleton of Lycorine-Type Alkaloids. In the course of photochemical studies on 1-aroylindoles, Carruthers and Evans (76) synthesized pyr-rolo[3,2,l-i/,e phenanthridin-7-one (35), the basic skeleton of lycorine, in 10% yield by irradiation of 1-o-iodobenzoylindole (34). However, photocyclization of the corresponding indole analogs proceeded quite differently as shown in Scheme 29. 

Lycorine-type alkaloids derived from pyrrolo[3,2,l-(ie] phenanthridine/ pyrrolophenanthridone ... 

On the basis of recent phytochemistry investigation about Amaryllidaceae alkaloids, anew 12-type classificatimi, including (1) norbelladine type, (2) lycorine type, (3) homolycorine type, (4) crinine and haemanthamine types, (5) tazettine type, (6) montanine type, (7) pUcamine type, (8) graciline type, (9) galanthindole type, (10) galanthamine type, (11) phenanthridone and phenanthridine types, and (12) other minor species populations, are deduced according to their ring systems. Representative structures for each type of Amaryllidaceae alkaloids are shown in Tables 17.2-17.13. 

Table 17.12 Phenanthridone- and phenanthridine-type Amaryllidaceae alkaloids...

Phenanthridone-type alkaloids have the highest oxygenated C ring in all Amaryllidaceae alkaloids, and they always show an amide group in ring B. On the contrary, alkaloids of the phenanthridine type often show completely aromatic ring system, occasionally with a methylation quaternary nitrogen atom, such as alkaloid bicolorine 214 (Table 17.12). 

Details have appeared of the earlier very interesting report which showed that tazettine (3 R = OMe, = H) is an artifact produced from pretazettine (2 R = OMe, R = H) during isolation. This type of rearrangement can be carried out with basic reagents also and applies with identical implications to the criwelline (3 R = H, R = OMe) -precriwelline (2 R = H,R = OMe) relationship. The interconversion of alkaloids possessing a 5,10h-ethano-phenanthridine nucleus (4) with those of the aforementioned [2]benzopyrano-[3,4-c]indole type (3) has been reported. Carefully executed experiments show that variation in temperature, solvent, or pH is sufficient to alter the ring systems... 

The pyrrolo[de]phenanthridine alkaloids (lycorine type) and the 2-benzopirano-[3,4-g]indole alkaloids (homolycorine type) both originate from an ortho-para phenol-oxidative coupling (Fig. 5). 

The alkaloids derived from 5,10b-ethanophenanthridine (crinine and haemanthamine types), 2-benzopyrano[3,4c]indole (tazettine type), phenanthridine (narciclasine type) and 5,11b-methanomorphanthridine (montanine type) originate from a para-para oxidative phenolic coupling (Fig. 9). 

The benzophenanthridine skeleton is encountered in approximately 30 alkaloids, principally of the family Papaveraceae (Cordell, 1978a). In contrast to the biosynthesis of protopine alkaloids, phenanthridine alkaloids are synthesized in the cytoplasm (Hartmann, 1991). This type of system arises from a protoberberine precursor by fission of the C-6-N bond and recyclization. The biogenetic sequence leading to chelidonine (80) biosynthesis in Chelidonium majus has been supported by feeding experiments with multiply-labeled (-t-)-reticuline [(5)-reticuline] (20) and with labeled stylopine (79) (Fig. 32.25) (Hutchinson, 1986 Sim ek, 1985 Tanahashi and Zenk, 1988). (5)-Z-V-Methylstylopine and protopine (60) have been shown to be metabolites in this pathway. Reticuline is oxidatively cyclized to ( —)-scoulerine (72). Formation of two methylenedioxy groups results in the formation of stylopine (79) (Hartmann, 1991). 

This type of Amaryllidaceae alkaloids owns an unique pyrrolo[t/,e]phenanthridine skeleton and is one of the most common alkaloids in plants of the family Amaryllidaceae (Table 17.3). Usually, they have a trans-junction in the B/C ring,... 

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