Tryptophan derivative construction

The construction of novel tetracyclic ring systems 1-142, which can be considered as hybrids of the I e Ira h y dropy r ro I o 12,3 - fo] i ndo le and tetrahydroimidazol[l,2-o]in-dole ring system, has been described by Herranz and coworkers [40]. The exposure of tryptophan-derived a-amino nitrile 1-140 to acidic conditions triggers a stereoselective tautomerization to give 1-142 in quantitative yield (Scheme 1.35). 

Unexpectedly, and very pleasingly, even the construction of 7-membered rings proved possible. Two examples are shown in Scheme 30 illustrating both a direct cyclisation and an addition-cyclisation sequence [66]. The first derivative 54, being ultimately derived from tryptophan, can be obtained in principle as an optically pure substance. The second is a simple approach to very rare polycyclic structures such as 55, only one example of which was documented in the Beilstein data bank. 

The Pictet-Spengler reaction has been combined with Ugi multi-component chemistry to construct a number of polycyclic indoles. Isonitrile derivatives prepared from tryptamine (or methyl tryptophanate), a carboxylic acid and formaldehyde condense with aminoacetaldehyde diethyl acetal. A few examples employed substituted aldehydes [352]. 

Indole-3-glycerol phosphate is the penultimate substrate which is fed into the tryptophan synthase complex. This enzyme is composed of two subunits (as an a2 and 2-tetramer) which utilizes substrate channeling to complete the construction of this amino acid. The a-subunit catalyzes the formation of indole from indole-3-glycerol phosphate and the -subunit catalyzes the condensation of indole to a serine-derived aminoacrylate moiety bound to pyridoxal monophosphate (PLP). 

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