Tryptophan formate

Modest enantioselectivity was observed for the P-replacement reaction catalyzed by 33-36 bilayer membranes [45]. D-Tryptophan formation prevailed over that of the l-form in 50-55 % ee regardless of chirality of the substrate, serine. Conversely, no enantioselectivity was observed when the 32 vesicle was used in place of 33. This suggested that the imidazolyl group of 33 might exercise stereospecific acid catalysis in the protonation of the prochiral carboanion intermediate. The enantioselectivity was also modest (ca. 30% ee) when the P-replacement reaction was mediated by the co-vesicle formed with 37,32, and an additional peptide lipid having (S)-binaphthol moieties (35) in the presence of Cu(n) ions. 

Other amino-acids which have been studied include L-cysteic acid mono-hydrate,which is conformationally similar to L-cysteine and taurine, and (—)-2-aA o-amino-norbornane-2-carboxyllc acid hydrobromide which has been shown to have the absolute configuration (li , 2R, AS). DL-Tryptophan formate exhibits an anti conformation about the C -Cp bond, in contrast to the gauche arrangement observed in the hydrochloride. 

Bruncko, M., Crich, D., and Sarny, R. (1994) Chemistry of cyclic tautomers of tryptophan formation of a quaternary center at C3a and total synthesis of the marine alkaloid (-F)-ent-debromoflustramine B. J. Oig. Chem., 59, 5543—5549. 

The crystal structure of DL-tryptophan formate was reported 67). There are no significant differences from the situation above described for L-tryptophan hydrohalides. 

Recently, the structure of the first N- and C-protected tryptophan derivative, i.e., N-acetyl-L-tryptophan methyl ester, was solved by Cotrait and Barrans (97). There is one hydrogen bond NH. .. O = C of 2.86 A between the NH indole group and the acetyl C = O of different molecules. Molecular packing in the crystal is established by van der Waals forces between the two hydrophobic methyl groups and the aromatic ring. The conformation of the tryptophanyl side chain is very close to that of the L form of DL-tryptophan formate. Fig. 5 shows bond lengths and angles of N-acetyl-L-tryptophan methyl ester. 

Bye, E., and C. Roemming Crystal Structure of DL-Tryptophan Formate. Acta Chem. Scand. 27, 471-484 (1973). 

Analytical applications of pyrazolones have been reviewed by Busev et al. (65RCR237). Organic bases are easily characterized by formation of highly crystalline salts with picrolonic acid (l-(4-nitrophenyl-3-methyl-4-nitro-5-hydroxypyrazole). The last-named compound is used as a reagent for alkaloids, tryptophan, phenylalanine and for the detection and estimation of calcium (B-76MI40404). 

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. 

Horse radish peroxidase, H2O2 or Laccase, pH 4, 2% DMSO or DMF. Cleavage occurs by the formation of a phenyldiimide, which decomposes to the acid, nitrogen, and benzene. The laccase method is compatible with the readily oxidized tryptophan and methionine because it does not use peroxide. ... 

For the kinetically controlled formation of 1,3-disubstituted tetrahydro-P-carbolines, placing both substituents in equatorial positions to reduce 1,3-diaxial interactions resulted in the cw-selectivity usually observed in these reactions." Condensation reactions carried out at or below room temperature in the presence of an acid catalyst gave the kinetic product distribution with the cw-diastereomer being the major product observed, as illustrated by the condensation of L-tryptophan methyl ester 41 with benzaldehyde. At higher reaction temperatures, the condensation reaction was reversible and a thermodynamic product distribution was observed. Cis and trans diastereomers were often obtained in nearly equal amounts suggesting that they have similar energies."... 

The intense blue color which is obtained when tryptophan, in the presence of an aldehyde, is treated with concentrated sulfuric acid containing an oxidizing agent (Adamkiewicz-Hopkins-Cole reaction) was beheved to involve formation of a tetrahydro-j8-carboline intermediate, since most l,2,3,4-tetrahydro-j8-carbohne derivatives yield a similar color with concentrated sulfuric acid containing an oxidizing agent. The two colors have now been shown to have different absorption spectra. The nature of the carboline-blue color is still obscure. 

The second line of circumstantial evidence quoted in support of this hypothesis is the ready formation of l,2,3,4-tetrahydro-/3-carboline derivatives under pseudo-physiological conditions of temperature, pH, and concentration. Tryptamine and aldehydes, trypt-amine and a-keto acids, and tryptophan and aldehydes condense at room temperature in a Pictet-Spengler type intramolecular Mannich reaction in the pH range 5.2-8.0 (cf. Section III, A, 1, a). It was argued that experiments of this type serve as models for biochemical reactions and may be used in evidence. 

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... 

During studies on ditryptophan derivatives, an interesting acid-induced cy-cHzation has been discovered. The 10-membered ring 37 was thus subjected to acidic conditions to produce the indolocarbazole derivative 38 (Scheme 6). Interestingly, calculations performed on the precursor 37 indicated that the lowest energy conformation resembled that of the diastereomer of 38, which was never observed. An additional experiment furnished the parent system 1 on treatment of 38 with a catalytic amount of acid. A TFA-induced formation of an indolo[2,3-<3]carbazole was also observed from a related acyclic 2,2 -connected tryptophan dimer (99JOC8537). 

The preferred formation of 261 over 260 is in accord with the well-known positional order 3 > 2 for reactivity of unsubstituted indole. Aiming at total synthesis of leptosin alkaloids, an application of this methodology to the 1-hydroxy-L-tryptophan derivatives seems to be promising. 

The structure of the complex of (S)-tryptophan-derived oxazaborolidine 4 and methacrolein has been investigated in detail by use of H, B and NMR [6b. The proximity of the coordinated aldehyde and indole subunit in the complex is suggested by the appearance of a bright orange color at 210 K, caused by formation of a charge-transfer complex between the 7t-donor indole ring and the acceptor aldehyde. The intermediate is thought to be as shown in Fig. 1.2, in which the s-cis conformer is the reactive one. 

The Pictet-Spengler reaction has mainly been investigated as a potential source of polycyclic heterocycles for combinatorial apphcations or in natural product synthesis [149]. Tryptophan or differently substituted tryptamines are the preferred substrates in a cyclocondensation that involves also aldehydes or activated ketones in the presence of an acid catalyst. Several versions of microwave-assisted Pictet-Spengler reactions have been reported in the hter-ature. Microwave irradiation allowed the use of mild Lewis acid catalysts such as Sc(OTf)3 in the reaction of tryptophan methyl esters 234 with different substituted aldehydes (aliphatic or aromatic) [150]. Under these conditions the reaction was carried out in a one-pot process without initial formation of the imine (Scheme 86). 

Figure 30-16. Formation of xanthurenate in vitamin Bg deficienqr. Conversion of the tryptophan metabolite 3-hydroxykynurenine to 3-hydroxyanthranilate is impaired (see Figure 30-15). A large portion is therefore converted to xanthurenate.

Phenoxazines — The two main types of phenoxazines are the ommochromes and the microbial phenoxazines. The biosynthesis of ommochromes occurs via the kynurenine pathway. The tryptophan amino acid is converted to formylkynurenine and then to kynurenine and 3-hydroxykynurenine. Not all the steps of ommochrome synthesis are completely elucidated yet. Ommatins are dimers and ommins are oligomers of 3-hydroxykynurenine. - The papiliochromes are derived from tyrosine as well as from the tryptophan pathway. The key intermediate in the formation of papiliochromes is N-beta-alanyldopamine (NBAD). Papiliochromes are synthesized in special wing scale cells, before melanins. " "... 

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