Tetrahydroberberine derivatives

In addition to the preparation of a- and /3-hydrastine described above from the betaine (64), another conversion of a tetrahydroberberine into hydrastine has been reported. Acetylophiocarpine, on treatment with ethyl chloroformate, gives the acetoxy-derivative of (88), which can be hydrolysed to the hydroxymethyl compound and then oxidized to the aldehyde by pyridinium perchlorate. Hydrolysis of the acetoxyl group afforded the hemi-acetal (93 R = H), conversion of which into the mixed acetal (93 R = Et) protected the aldehyde system during reduction of N—C02Et to NMe by lithium aluminium hydride. Hydrolysis of the acetal, followed by oxidation, then gave a-hydrastine, and a similar sequence of reactions starting from O-acetyl-13-epi-ophiocarpine afforded / -hydrastine.119 Methods of synthesis of alkaloids of this group have been reviewed.120... 

Tetrahydropalmatine has strong analgesic, sedative, and hypnotic effects 544, 553-563). They are produced by the (—) type hut not by the (+) type. In rabbits the analgesic effect was weaker than that of morphine, but the tolerance for this drug developed at a far slower rate practically without any side effects. In experiments on patients tetrahydropalmatine had a weaker analgesic effect but a stronger hypnotic effect than morphine. Application of doses of 10 mg/kg of tetrahydropalmatine to white mice led to disappearance of the conditioned reflexes whereas the unconditioned reflexes were maintained. For the influence of (+ )-tetrahydropalmatine and other alkaloids on gastric ulcers in experimental animals, see Soji et al. (564). Variously substituted tetrahydroberberine and tetrahydropseudoberberine derivatives act as tranquilizers (565-569). 

An improved method for the removal of methylenedioxy-groups in alkaloids of the benzylisoquinoline and tetrahydroberberine series has been derived. Alkaloids such as remneine (26) can be converted into the dihydroxy-bases (27) by treatment with boron trifluoride followed by 5-chloro-5-phenyl-l//-tetrazole and subsequent hydrogenolysis of the resulting bis-tetrazolyl ethers. The yields in the process are good.39... 

A route to /3-methyl-tetrahydroberberines has been developed from the hydra-stinine derivative (72), which can be acylated with the dimethoxyhomophthalic anhydride (73) to give acid (74). Reduction of this with lithium aluminium hydride followed by further reduction of the toluene-p-sulphonyl ester of the resulting hydroxymethyl compound yields the 13-methyl compound.91 An essentially similar synthesis of oxoberberines bearing a carboxy-group at C-13, of general type (74), has been reported by other workers.92... 

Several alkaloids based on the isoindoloisoquinoline, isoind-olobenzazepine, isoindolobenzazocine and isoquinolinobenzaze-pine skeletons have been discovered. In all of these except two the aromatic substitution pattern is the same as that in tetrahydroberberine, the exceptions being related to tetrahy-dropalmatine. They are assumed to be derived from alkaloids of the berberine series, from which some transformations have been effected. 

Berberrubine was converted to hunnemanine by the procedure used by Perkin to convert tetrahydroberberines into protopines. The free hydroxyl was protected as its benzyl derivative 108). 

A structure-activity analysis has been made of tetrahydropapaveroline and its derivatives, certain tetrahydroberberines, and aporphines to determine whether... 

The mass spectra, high-resolution n.m.r. spectra, and fluorescence spectra of tetrahydroberberines and some of their derivatives have been studied. 

---