Tetrahydroprotoberberine alkaloids

The tetrahydroprotoberberine alkaloids have a tetracyclic ring structure which is based on the dibenzo[a,g]quinolizidine system (Fig. 12). Carbon-13 NMR has been used extensively to study the quinolizidine conformation... 

Corydalic acid methyl ester 11, isolated from Corydalis incisa, is derived from a proposed biosynthetic intermediate in the route to the tetrahydroprotoberberine alkaloids. The 1,2,3,4-tetrasubstituted ring of 11 demands control by an ortholithiation strategy, and the synthetic route proposed by Clark and Jahangir2 employs a lateral lithiation of 12 and addition to an imine as the key disconnection at the centre of the molecule. 

A knowledge of the stereochemistry of corydaline and mesocorydaline has permitted stereochemical assignments to be made to the other known 13-methyl-substituted tetrahydroprotoberberine alkaloids (105). 

II) t3q>es. The absolute configuration of (-f )-norlaudanosine was elucidated by adopting a degradative method (isolation of i T-a-carb-oxyethyl-L-aspartic acid) 115), which in turn permitted the establishment of the absolute configuration of the proaporphine, aporphine, pro-morphinane, morphinane, and tetrahydroprotoberberine alkaloids (Scheme 20). The optical rotatory data 63), the ORD-curves 2, 41,120, 122), and the CD-curves 73) have led to an accumulation of sufficient information for the determination of the absolute configuration even of... 

The NMR spectroscopy, mass spectrometry, and the biosynthesis (Scheme 2) of the tetrahydroprotoberberine alkaloids were described in detail in The Alkaloids, Vol. IX, Chapter 2 and in various publications... 

Recently, attention has been paid to the photosynthesis of tetrahydroprotoberberine alkaloids (131, 282) from iV -acetyl-l-benzylidenetetra-hydroisoquinolines (a) and from bases of protopine type (b) which proceeds along the two pathways shown in Scheme 8. 

Analysis of the extracts of different collections of Theonella sponge resulted in the isolation of the first example of marine occurring brominated benzyl tetrahydroprotoberberine alkaloid, theoneberine (81)... 

Scheme 7. Pathway for the formation of thalphenine (32) from tetrahydroprotoberberine alkaloids (58) (429).

A short time back a series of tetrahydroprotoberberine and pro-toberberine alkaloids (vide infra) and their methohydroxides were isolated. Those isolated from plants of the family Papaveraceae can be subdivided into tetrahydroprotoberberine alkaloids of the type 58, their dehydro derivatives 59, 13-methyltetrahydroprotoberberine (68) (dehydro derivatives 69), and 13-hydroxytetrahydroprotoberberine (70). Alkaloids of the caseanadine type (62), the tetrahydropseudoprotoberberine alkaloids (60,64) (their dehydro derivatives 61, 63, and 65 have not been found in nature as yet), the corytenchirine (83) type, and 66 with the dehydro derivatives 67 were also isolated. Included in the last group is the alkaloid aryapavine (66b) which was recently isolated from P. pseudoorientale (243, 587). The alkaloids of the types 58 and 59 are subdivided still further according to whether they possess two or three electron-donating oxygen substituents on the ring A. 

The tetrahydroprotoberberine alkaloids with three oxygen substituents located in the ring D have been found in Stephania rotunda (Menisper-maceae) (588). These types of alkaloids will probably be helpful in future chemotaxonomy. 

During the past years, the isolation of a great number of quaternary bases of the already known tetrahydroprotoberberine alkaloids has been reported (Table X) (32, 158, 158a, 183, 246). The escholidine perchlorate thus isolated was shown to be 2,3-methylenedioxy-9-methoxy-10-hydroxy-tetrahydroprotoberberinium methoperchlorate (155). As shown by 13C NMR spectroscopy, quaternary tetrahydroprotoberberine alkaloids may have the a- and /8-form of the conformation. 

The isolation of (— )-iV-methylstylopinium chloride from Papaver rhoeas represents the first time that a quaternary tetrahydroprotoberberine alkaloid has been isolated from the Papaver genus. Treatment of this alkaloid with base in DMSO solution gave the Hofmann product (149). This type of product has not been obtained by Hofmann degradation of JV-methyltetrahydrober-berinium or iV-methyltetrahydropseudoprotoberberinium alkaloids. Of the alkaloids isolated from Thalictrum polygonum, only berberine was shown to exhibit weak antimicrobial activity.The alkaloid content of Chelidonium majus was studied as a function of the drying procedure of the plant. ... 

The conformational assignment in dibenzo[a, ]quinolizidines (tetrahydroprotoberberine alkaloids) in CDCI3 is hampered by coincidence of the signals due to the CH angular proton and OMe groups present in most of them. However, use of deuterotoluene as solvent causes a dovrafield shift of methine proton and permits its analysis. Typical d and 7 values for these protons are cK-isomers, S = 4.25-4.31 ppm, dd, J= 12 and 4 Hz rrani-isomers, S 3.50-3.96 ppm, dd, J= 15 and 4 Hz <770MR(9)341>. 

McMurtrey, K. D., Cashaw, J. L., and Davis, V. E., 1980, Analysis of dopamine-derived tetrahydroisoquinoline and tetrahydroprotoberberine alkaloids by cation-exchange liquid chromatography,/. Liq. Chromatogr. 3 663-679. 

The C-8 methylated tetrahydroprotoberberine alkaloids coralydine and 0-methylcorytenchirine have also been synthesized via benzocyclobutene thermolysis followed by reduction. ... 

This generalization has recently been used to correct the structures of a variety of tetrahydroprotoberberine alkaloids. Aequaline was shown to be identical with discretamine, and coramine with coreximine. Schefferine is the same as kikemanine, and discretinine corresponds to corypalmine. ... 

The biogenesis of ochotensimine has been studied in Corydalis ochotensis (Fumariaceae), and in conjunction with that of the tetrahydroprotoberberine alkaloid corydaline in C. solida. Both compounds are derived from two molecules of tyrosine and the 5-methyl group of methionine. The 5-methyl group of methionine supplies, among others, the C-13 methyl group of corydaline and the exocyclic methylene group of ochotensimine. (See also Sec. 19.4.)... 

Tetrahydroharman, K16 Tetrahydroharmine, K16 Tetrahydroisoquinoline alkaloids, K1-2 Tetrahydrolinalool, T3 Tetrahydroprotoberberine alkaloids,... 

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