The Phthalideisoquinoline Alkaloids

Abstract

Classical type phthalideisoquinolines are derived biogenetically from tetrahydroprotoberberines, and the former in turn lead to the secophthalideisoquinolines. The secophthalideisoquinolines may come in different forms including enol lactones, keto lactones, keto acids and diketo acids. The most logical biogenetic sequence appears to be classical type phthalideisoquinoline-^classical type phthalideisoquinoline .Y-metho salt->secophthalide enol lactone->secophthalide keto acid->secophthalide diketo acid. Thus if one were to start with (-)-bicuculline (1), the sequence would be 1-»( -)-bicuculline .Y-metho salt (la)->the Z enol lactone aobamidine (32)->the keto acid adlumidiceine (36)->the diketo acid bicucullinine (42) (100). A seco diketo acid may then undergo oxidative cleavage to yield the alkaloid fumariflorine (51), or one of its analogs. Alkaloids of the fumariflorine type may thus represent a final stage in the catabolism of the phthalideisoquinolines (101). It is worth noting here that the presence of classical type phthalideisoquinoline .Y-metho salts has been detected in Fumaria parviflora Lam. ( 70).An enol lactone such as aobamidine (32) may undergo photoisomerization to a mixture of Z and E isomers, and in fact the E analog of aobamidine is known as a natural product under the name adlumidiceine enol lactone (33).It has recently been shown that secophthalideisoquinoline enol lactones readily react with ammonia to form hydroxy lactams (e.g. fumschleicherine (50) ). A secophthalide hydroxy lactam can then undergo facile dehydration to an enelactam. Four enelactams have been apparently isolated from natural sources, namely, fumaramine (45), fumaridine (46), fumaramidine (48), and narceine imide (49). Since ammonium hydroxide is usually used in the course of the isolation, it seems likely that these four compounds, together with fumschleicherine (50), are artifacts of isolation. Until and unless the presence of secophthalideisoquinoline hydroxy lactams and enelactams is conclusively demonstrated in the plant extracts prior to treatment with ammonia, it can be concluded that they are artifacts and not true alkaloids (100). Nevertheless, and for the sake of completeness, the hydroxy lactam fumschleicherine (50) and the four enelactams 45, 46, 48, and 49, have been included in the present listing.The secophthalideisoquinoline keto acid nornarceine (40) may also be another artifact. It is the only known seco base which does not incorporate a complete ,. -dimethylaminoethyl side chain. It was isolated only once, and that time from opium, and it may very well have arisen from the known in vitro N-demethylation of narceine (39) in acid solution (100).All uv data are in nm with log < values between parentheses. Ir frequencies are in cm-1.The nmr chemical shift values quoted are from the first reference cited. However, in case we have found it necessary to modify the original assignment, this has been indicated by a double asterisk (**) as a superscript immediately after the reference. Whenever possible, we have ...

Antimalarial alkaloids from a Bhutanese traditional medicinal plant Corydalis dubia

“…Other known compounds 2-8 were identified through MS library matching techniques (NIST08s) and subsequent comparison of their melting point, optical rotation, mass spectra and NMR spectra ( 1 H and 13 C) with those reported. Compound 2 was identified as scoulerine (Brochmann-Hanssen, Nielson, 1966;Cheng et al, 2008), compound 3 as cheilanthifoline (Okamoto et al, 1971;Haisova and Slavik, 1973;Yeola and Mali, 1984;Rucker et al, 1994;Cheng et al, 2008), compound 4 as protopine (Abou-Donia et al, 1980;Takahashi et al, 1985;Seger et al, 2004), compound 5 as capnoidine Ribar and Meszaros, 1991;Pilar et al, 2010) whose structure was also confirmed from a X-ray crystal structure (not shown here), compound 6 as bicuculline (Edwards and Handa, 1961;Abou-Donia et al, 1980;Blasko et al, 1982;Elango et al, 1982;Basha et al, 2002), compound 7 as corydecumbine (Basnet et al, 1993) and compound 8 as hydrastine Elango et al, 1982).…”

(-)-β-Narcotine: A Facile Synthesis and the Degradation with Ethyl Choroformate

“…Some of these ringcleaved products are known to be present in nature as secophthalideisoquinolines. 12 In our previous report, 13 we demonstrated that (-)-β-narcotine (6) was degraded by ethyl chloroformate at room temperature to give the carbinol 8 via the chloro-carbamate 6b as a colorless crystalline material, which, however, could not be completely purified. The carbinol 8 was at that time separated by preparative TLC to furnish each diastereomeric pair with an approximate ratio of 5 : 1 (NMR analysis).…”

Hydrastine Pharmacokinetics and Metabolism after a Single Oral Dose of Goldenseal (Hydrastis canadensis) to Humans

“…The primary alkaloids with known biologic activity are the phthalide isoquinoline alkaloid (1-R, 9-S)-b-hydrastine and the quaternary protoberberine-type alkaloid berberine (Weber et al, 2003). Goldenseal is unique from other hydrastine-containing plants in that (2)-b-hydrastine is the only hydrastine isomer present, while the (+)-enantiomer is found in other hydrastine-containing plants (Blaskó et al, 1982). While a number of therapeutic activities have been attributed to berberine, the pharmacological effects of hydrastine are less studied and its safety profile is poorly understood to frame the relevant pharmacological effects of hydrastine within the specific stereochemistry found in goldenseal.…”