Phenanthridone alkaloids

Crinasiadine, N-Methylcrinasiadine. Two simple phenanthridone alkaloids, crinasiadim (27) [12] and N-methylcrinasiadine (28) [13] (Scheme 6) were prepared [9] from a commor intermediate, the chloro compound 21. 

A new alkaloid phamine (430), which is a phenanthridone alkaloid belonging to the narciclasine group, has been isolated from the bulbs of Hippeastrum equestre along with known Amarylldaceae alkaloids (47). Its structure was determined by spectroscopic (MS, UV, H and NMR) analyses. Also, phamine indicated interesting antimitotic activity. The alkaloids isolated since 1987 are shown in Fig. 25. 

Coupling of amino cyclohexene derivative 100 with 6-bromopiperonylic acid (101) provides amide 102, which is a key intermediate for the synthesis of phenanthridone alkaloid lycoricidine (103).39... 

The phenanthridone alkaloid, lycoricidine 64 fScheme 12.32). is known to possess cytotoxic activity. Based on the retrosynthetic analysis as discussed in Section 12.3.2 f Scheme 12.18T the Chida group reported the total synthesis of lycoricidine starting from d-glucose in which the Ferrier carbocyclization reaction was enployed as the key reaction. For the preparation of the cyclohexene unit in lycoricidine, d-glucose was converted into 2-azido-d-altropyranoside derivative 122 via epoxide 121 fScheme 12.31T Protection of the diol moiety in 122 afforded 68, which was transformed into 5-enopyranoside 67 by the action of DBU. Ferrier carbocyclization of 67 with 1 mol% of Hg(OCOCF3)2, followed by p-elimination,... 

Narciprimine (Fig. 49.7) is the known phenanthridone alkaloid isolated from Cyrtanthus contractus N.E. Br. (fire lily) (Amaryllidaceae). In in vitro experiments [66], it exhibited strong AChE inhibition with IC50 value of 78.9 pM. In that study, presence of narciprimine was shown for the first time in the genus... 

A. Padwa, H. Zhang, Synthesis of some members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family, J. Org. Chem. T1 (2007) 2570. 

The synthetic plan for an antitumor alkaloid, lycoricidine 64, based on the Ferrier carbocyclization is shown in Scheme 12.18. The tricyclic phenanthridone skeleton was envisioned to be constructed by C—C bond formation between C-lOa and C-lOb by a transition metal-catalyzed sp -sp carbon coupling reaction. The C-ring 65 possessing an... 

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). 

With N-methylbenzamides, the yields of substitution products are lower. > The S j l reaction between substituted o-iodobenzamides and the enolate anion of 2-acetylhomoveratic acid can be used for the synthesis of derivatives of the benzo(c)-phenanthridone and berberine alkaloids. ... 

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