Tryptophans formaldehyde

In view of its possible interest as the mode of formation of harman, harmine and harmaline in plants, Kermack, Perkin and Robinson investigated the conversion of tryptophan (II) into harman (I) and nor-harman (IV). The latter is produced when tryptophan is condensed with formaldehyde in presence of dilute sulphuric acid and the product (III) oxidised by potassium dichromate. Harman is formed when formaldehyde in this process is replaced by acetaldehyde. 

The reactions of tryptophan and of tryptamine derivatives with formaldehyde require special comment. Whereas tryptamine and its 5- and 7-methoxy and i id-A-methyl and -ethyl derivatives react... 

Depending on conditions, formaldehyde and tryptophan yield either 1,2,3,4 - tetrahydro-jS - carboline-3-carboxylic acid (17 R = H), or the intermediate carbinolamine (16, R = H), which... 

Carboline derivatives in various oxidation states have been isolated from a number of natural sources as artifacts. )3-Carboline has been obtained from charred insects, j8-carboline and l-methyl-)3-carboline have been found in cigarette smoke,and the formation of tetrahydro-j8-carboline derivatives has been shown to be responsible for the destruction of tryptophan in acid hydrolyzates of proteins. The golden-yeUow fluorescence observed when enterochromaffin cells are flxed in formaldehyde has been related to their content of... 

Conversion of methanol into formaldehyde by methanol dehydrogenase. A complex array of genes is involved in this oxidation and the dehydrogenase contains pyrroloquinoline quinone (PQQ) as a cofactor (references in Ramamoorthi and Lidstrom 1995). Details of its function must, however, differ from that of methylamine dehydrogenase that also contains a quinoprotein—tryptophan tryptophylquinone (TTQ). 

In dilute aqueous solution, formaldehyde can react with a variety of amino acids. However, the primary initial targets are lysine and cysteine. The primary amine moiety of lysine can accept two methylol adducts. Other amino acids with which formaldehyde reacts include arginine and tyrosine, which are particularly reactive, as well as histidine, serine, tryptophan, glutamine, and asparagine.2 ... 

Many recent studies have focused on the mechanisms of formaldehyde modification, cross-linking, and reversal.19,37 8 In general, these studies found that formaldehyde is very specific, particularly when reaction times are relatively short. The amino-termini, lysine, tryptophan, and cysteine are the targets of modification in this case. Longer reaction times reveal more extensive modifications, including arginine, histidine, tyrosine, and phenylalanine. 

Pictet-Spengler cyclization of L-tryptophan with formaldehyde afforded the monochiral carboxylic acids 20a,b, whereas cyclization with acetaldehyde yielded the diastereomeric carboxylic acids 21a,b (23). Acids 20a,b with a hydrogen at C-1 are enantiomers, but acids 21a,b are diaste-reomers the cis isomer 21a was the major reaction product when the cyclization of L-tryptophan with acetaldehyde was carried out in the presence of sulfuric acid. Direct removal of the carboxy group in these acids is difficult, but it can be accomplished in several steps dehydration of the amides prepared from the acids with phosphorus oxychloride affords nitriles, and the nitrile group can be removed by reduction with sodium borohydride in pyridine-ethanol (31). 

The enzyme has also been used in the production of several natural amino acids such as L-serine from glycine and formaldehyde and L-tryptophan from glycine, formaldehyde, and indole [77-79], In addition, SHMT has also been used for the production of a precursor, 20, to the artificial sweetener aspartame (21) through a non-phenylalanine-requiring route (Scheme 14) [80-83]. Glycine methyl ester (22) is condensed with benzaldehyde under kinetically controlled conditions to form L-enY/ ra-p-phenylserine (23). This is then coupled enzymatically using thermolysin with Z-aspartic acid (24) to form A -carbobcnzyloxy-L-a-aspartyl-L-eryt/zro-p-phenylserine (20). and affords aspartame upon catalytic hydrogenation. 

Conversely, indole can be condensed with the Mannich base from nitro-malonic ester, formaldehyde, and ammonium acetate, giving an intermediate that can be worked up to give an overall yield of tryptophan of 77% 815... 

Poindexter and Carpenter (2972) reported the isolation and identification of 9//-pyrido[3,4-/>]indole (norharman) and l-methyl-9//-pyrido[3,4-/>]indole (barman) from CSC. They reported that the yield of the total barmans in hurley and flue-cured MSSs was between 15 and 20 xg/gram of tobacco smoked, values which were 40 to 50 times that of the barmans in the unsmoked tobacco. Since the weight of tobacco in cigarettes sold at that time approximated 1 gram, the yield of these two compounds was about 15-20 Xg/cig. Poindexter and Carpenter concluded from experiments with radiolabeled tryptophan that the barmans (found to be radiolabeled in the smoke) were generated pyrogenetically from a reaction between aldehydes (formaldehyde for norharman, acetaldehyde for barman) and the tryptophan in tobacco. 

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