Dopamine Pictet-Spengler condensation with

Some aldehydes require special reaction conditions, e.g. chloral (14), which, due to extended hydration, does not undergo a Pictet-Spengler reaction with dopamine (11) in aqueous solution but can be condensed very efficiently in organic acids, such as trifluoroacetic acid, to give the 1-trichloromethylte-trahydroisoquinoline (15) in high yield (Scheme 10). ... 

Several C-nucleosides have been prepared by Pictet-Spengler condensations between biogenic amines, such as dopamine hydrochloride 198 with D-glucose 199 to give 200 (83CJC2721). 

Salsolinol, as well as the benzylisoquinoline tetrahydropapaveroline, are inhibitors of dopamine 0-methylation in vitro, since they themselves are metabolized by 0-methylation catalyzed by catechol 0-methyltransferase (COMT). They are also in vitro inhibitors of rat brain monoamine oxidase. Both compounds were isolated in significant concentration from the urine of patients with Parkinson s disease during oral L-dopa treatment. The formation of these alkaloids probably originates from a Pictet-Spengler condensation of dopamine with the required aldehyde. ... 

To date, biosynthetic pathway for four classes of plant alkaloids has been characterized to some extent the benzylisoquinoline, monoterpenoid indole, purine, and tropane alkaloids. Benzylisoquinoline alkaloids (BIAs) are derived from tyrosine and are comprised of 2,500 defined structures found mainly in the Papaveraceae, Ranunculaceae, Berberidaceae, and Menispermaceae [11]. First step of BIA biosynthesis begins with the stereoselective Pictet-Spengler condensation of dopamine and 4-hydroxyphenylacetaldehyde to form (5)-norcoclaurine. Subsequently, through a series of methylations and hydroxylations, (5)-norcoclaurine gets converted into (5)-reticuline, which is the pivotal intermediate for many pharmaceutically important BIAs formed further down in the pathway (i.e., downstream pathways) (Fig. 8.6) [3]. 

Pictet-Spengler condensation of dopamine with D-glucose gave a 4 1 mixture of 1-substltuted tetrahydroisoquinoline diastereomers (43). Analogous reactions of dopamine and tryptamine with 2,5-... 

The biosynthesis of optically active TIQs, exemplified by the presence of ( )-salsolinol in human fluids (189b), requires some comment. This is particularly warranted since many investigators have concluded that the conversion of dopamine to TIQ 64b is the result of condensation of the amine with acetaldehyde originating directly from ethanol. As shown in Fig. 32, this reaction, when carried out in vitro, affords racemic salsolinol (64) (5a,10). Formation of optically active TIQ 64b from dopamine and acetaldehyde would require that the Pictet-Spengler reaction be enzymatically controlled, as observed in the condensation of dopamine with 4-hydroxyphenylacetaldehyde in benzylisoquinoline-producing plants (209). The enzyme required to perform this reaction in mammalian systems has not yet been found. There are several observations which dispute such a reaction taking place in mammals the finding of 1-carboxy-TIQ 91 and DIQ 69 as major metabolites (189) and the very low levels of acetaldehyde detected in the brains of animals after alcohol consumption (215,216). This makes the acetaldehyde route to optically active 1-methyl-substituted TIQ suspect. 

Phenethylisoquinoline alkaloids constitute another important group of tyrosine-derived secondary metabolites. This class of natural products with colchicine (54) as most prominent member is obtained when aldehyde 43 is employed in a condensation reaction with dopamine, followed by a Pictet-Spengler cyclization reaction. The difference to benzyltetrahydroisoquinoline alkaloids is an additional carbon between the tetrahydroisoquinoline core and the aromatic ring. As outlined in Scheme 12.9, aldehyde 43 is derived from phenylalanine (42) via intermediary formation of 4-hydroxycinnamaldehyde. The formation of the tetrahydroisoquinoline system 44 from dopamine (4) and 4-hydroxydihydrocinnamaldehyde (43) is followed... 

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