Berberine, proto

Berberine, proto l-8-dihydroxy-2-3-9-10-dimethylenedioxy Berberine, proto-2-3-9-10-imethylenedioxy-8-oxo Berberine, tetrahydro... 

On treatment of N-methylpapaverine, formed by the lithium aluminum hydride reduction of papaverine methiodide with phosphoric acid, N-methylpavine is formed which is identical with the racemic alkaloid argemonine. This reaction was used for the synthesis of the alkaloid (-h)-coreximine (268) (174) and similar compounds containing the proto-berberine grouping in the molecule (269,270). 

Scheme 16. Synthesis of polyberbine (66), polycarpine (67), and its analog from proto-berberines. Reagents a, MCPBA, NaHCQ3, CH2C12, -78°C b. MCPBA, NaH, THF.

Indenobenzazepines have been used as key intermediates for synthesis of rhoeadine, protopine, phthalideisoquinoline, and spirobenzylisoquinoline alkaloids. Several new alkaloids possessing an indenobenzazepine skeleton have been isolated, and they are presumably biosynthesized from proto-berberine alkaloids. 

Protoberberine Alkaloids.—In the course of the bioconversion of the proto-berberine scoulerine (65) into chelidonine (62) and phthalide-isoquinolines, e.g. narcotine (63), C-13 becomes oxidized.61 Ophiocarpine (68), with a hydroxy-group at C-13, represents an intermediate stage in the modification of the protoberberine skeleton, and results62 of tracer experiments have shown that scoulerine (65) is also to be included in the biosynthesis of this alkaloid. Tetrahydro-protoberberine (67) is also a precursor, its incorporation indicating that C-13 hydroxylation is a terminal step. As for other protoberberine derivatives,63 nandinine (64) was not assimilated,62 and it follows then that (65) is probably converted into (67) by way of isocorypalmine (66). 

Scheme 3, p. 15, in ref. 7). As discussed below, protopine (73) and (81) are precursors for rhoeadine (83) and alpinigenine (82), respectively modified proto-berberines in which further C—N bond cleavage must also occur. In this case it is the C-8—N bond [as (73)] which must be broken, whereas in the case of chelidonine (62) it is finally only the C-6—N linkage. 

Degradation of the active chelidonine established the position of the labels as shown in CII, in agreement with its derivation from the proto-berberine ring system as suggested first by Sir Robert Robinson 131), and later by Turner and Woodward in Volume III, page 54. Furthermore, the absence of tritium is in keeping with the proposed intermediacy of the dihydroisoquinoline (CIII) (see Chart VIII). 

The thermal decomposition of tetrahydroberberine methine base hydrochloride has been shown to yield an epimeric mixture of the rearranged product (216).215 An interesting transformation of a protoberberine into a benzophenanthridine alkaloid is discussed in Section 3J. Other work dealing with the synthesis of proto-berberine-type structures has been reported.216—218 A procedure for the preparation of radioiodinated (131I) berberine has appeared.219... 

Two intriguing models for the biogenesis of spirobenzylisoquinoline alkaloids have been proposed.246,247 Knowledge that aurotensine (265) and other proto-berberine-derived alkaloids co-occur with ochotensine, a spirobenzylisoquinoline... 

Various Reactions in the Side-Chains of Thiophens. - The preparation of various iV-substituted thieno[3,2-/]morphans from 2,5-dimethylthieno[3,2-/Jmorphan has been described. Several thiophen isosteres of proto-berberine alkaloids have been prepared, starting from amides between 3-thienylacetic acid and substituted )3-phenylethylamine or 3-(3-thienyl)ethyl-amine, followed by classical cyclization to dihydroisoquinolines, reduction to the tetrahydro system, and Mannich-type reaction with formaldehyde. 

A new tetrahydroprotoberbine alkaloid is tetrahydrothalifendine (132), found in Thalictrum fendleri Engelm. ex Gray (Ranunculaceae). The first known dimeric proto berberine alkaloid is bisjatrorrhizine (133), obtained from the root of Jatrorrhiza palmata (Lam.) Miers (Menispermaceae) and synthesized by oxidative dimerization of jatrorrhizine. ... 

FIG. 2 Biosynthetic pathway leading from (S)-reticuline to the proto-berberine alkaloids in Berberis and Coptis. 

This group of about 40 alkaloids is known only from the Papaveraceae (Guinaudeau and Bruneton, 1993 Ronsch, 1986). These compounds probably are derived from proto-berberine precursors (Santavy, 1979). (13R)- and (135)-scoulerine (72) are converted in plants of Papaver rhoeas into rhoeadine (89) (Fig. 32.29). This alkaloid had lost 79% of the tritium label from the (135) precursor, whereas the alkaloid retained 74% of the label from the (13/ ) precursor. Although the starting materials were not completely confor-... 

Incorporation studies of Corydalis solida Sw. (Fumariaceae) fed with [3- C]-tyrosine and [methyl- C]-methionine as well as [methyl-T, C]-methionine indicated that methionine supplies the A carbons of the proto-berberine corydaline and the spirobenzylisoquinoline ochotensimine. ... 

Kametani, T., Takagi, N., Toyota, M., Honda, T., and Fukumoto, K., Total synthesis of the proto-berberine alkaloid (-)-xylopinine by photochemical 1,3-asymmetric induction, /. Chem. Soc., Perkin I, 2830-2834,1981. 

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