Tiglic acid from isoleucine

It has been confirmed that isoleucine but not 3-hydroxy-2-methylbutanoic acid is a precursor for the tiglic acid which is the esterifying acid in some tropane alkaloids [e.g., meteloidine (77) (735)]. In the biosynthesis of meteloidine (77) from 3a-hydroxytropane (1), the hydroxyl groups at C-6 and C-7 are most probably introduced after esterification at C-3 (5) (Scheme 23). In this connection we would point out that scopolamine (89) is a well-known 2,3) metabolite of hyoscyamine (27) and that the reaction proceeds via 6-hydroxyhyoscyamine [(—)-anisodamine (63)] and 6,7-dehydrohyoscyamine (211) (Scheme 26). 

Besides tropic and phenyllactic acids, little is known about the biosynthesis of other acids esterifying the tropane nucleus. Leete [26] listed the acids found in tropane alkaloids whose biosynthesis has been studied, usually by feeding labelled precursors to intact plants. Thus, tiglic acid, the acidic moiety of tigloidine and meteloidine, has been shown to be derived from the amino-acid L-isoleucine, probably via 2-methylbutanoic acid [38],... 

Tropane Alkaloids.—Previous research had shown that the tiglic acid (55) moieties of the ester alkaloids of Datura species, e.g. (56), (57), and meteloidine (58), arise specifically from L-isoleucine (52). " This amino-acid is also a source for angelic acid (the geometric isomer of tiglic acid) in Cynoglossum officinale and it is degraded in animal tissues to tiglic acid, probably by way of 2-keto-3-... 

Tiglic acid is found as the esterifying acid in a number of tropane alkaloids, e.g. 3a-tigloyloxytropane (13). It is known to be derived from L-isoleucine via... 

The biosynthesis of the tigloyl [as 6.75)] residues of, e.g., meteloidine 6.75), has been found to be similar to that leading to tiglic acid in animals. It derives from the amino acid L-isoleucine [58-60]. 

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