Hygrine hyoscyamine

L-metilionine to -adenosylmethionine. In this process a positively charged sulphur is produced and facilitates the nucleophilic reaction. By the activity of diamine oxidase, the A -methyl-A -pyrrolinium cation is formed and after that the first alkaloid, hygrine. From hygrine, by way of acetyl CoA, hydrolysis and intramolecular Mannich reactions, other pyrrolidine and tropane alkaloids are synthesized cuscohygrine, hyoscyamine or tropinone, tropine and cocaine. The Mannich reaction involves the combination of an amine, an aldehyde or a ketone with a nucleophilic carbon. This reaction is typical in alkaloid synthesis, and can be written as follows ... 

It has been shown that putrescine was incorporated into hyoscyamine (46) however, it was predicted that certain enzymes are capable of converting putrescine into N-methyl putrescine which is an established precursor of tropine (43). It has also been reported that ( +)-(2R)-hygrine serves as a precursor of the tropane alkaloids of Datura innoxia (47), this is true as (2i )-hygrine is formed by an attack of the acetoacetate on the pyrrolinium salt (43) as it is evident from the biosynthetic scheme of hyoscyamine. 

The results with [l- C]acetate in S. lurida support this conclusion. Incorporations for this precursor as well as [2- C,<5- N]ornithine, [l,4- C2]putrescine, and [4- H]-iV-methylputrescine were recorded in both cuscohygrine (29) and hyoscyamine (30). Degradation of the cuscohygrine in each case, which was to hygrinic acid (31), showed that the activity from these precursors (excluding acetate) was confined almost entirely to the pyrrolidine ring. 

The biosynthesis of alkaloids containing a pyrrolidine ring such as hyoscyamine (18) and hygrine (19) is similar to the biosynthesis of those with a piperidine... 

Hygrine occurs in Erythroxylon truxillense Rusby leaves in extractable quantities, but not in those of other tropane-forming species. It could be equally well regarded either as an intermediate substance or an unmanageable side product. Difficulties in realizing its oxidation have led to the suggestion of yet another possible precursor of hyoscyamine in diamino-adipic acid. When this is done the difficulty of the intermediate oxidation disappears, but the origin of the diaminoacid puts another in its place. 

Tropane Alkaloids,—Hygrine [as (11)] is a proven precursor for tropane alkaloids, e.g. hyoscyamine (12). It has now been shown further that (+)-hygrine (11) is much preferred over its enantiomer as a substrate for elaboration of tropane alkaloids, e.g. (12), in Datura innoxia. On the other hand (+)-hygrine was only slightly preferred for the formation of cuscohygrine (14). 

Quantitative information concerning simple pyrrolidine alkaloids is rather rare. The roots of Nicandra physalodes contained 0.1% hygrine whereas five Physalis spp. contained considerably less (Romeike 1965a,b). The content of the epigeal parts of N. physalodes was even extremely low. Surprisingly, cuscohygrine turned out to be the main alkaloid of Datura discolor roots with a concentration of 0.06% which amounts to 20% of the total alkaloid content (0.31%). This is in contrast with other Datura spp. where tropanes (hyoscyamine/scopolamine) represent the principal alkaloids (Evans and Somanabandhu 1974a). 

O Donovan DG, Keogh MF (1968) Biosynthesis of piperidine alkaloids. Tetrahedron Lett 265-267 O Donovan DG, Keogh MF (1969) The role of hygrine in the biosynthesis of cuscohygrine and hyoscyamine. J Chem Soc C 223-226... 

Hydroxytremetone, Y1 2-hydroxytryptophan, A20 5-hydroxytryptophan, A20 Hygrine, K19 Hygrinic acid. All Hygroline, K19 Hygrophyllinecic acid, K23 Hymentherenes, Tl Hyoscine, K28 Hyoscyamine, K28... 

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