Indole chromophore

The biogenetic approach, which is a linear approach, is based on the stepwise disconnection of 18 into a series of biogenetically related alkaloid precursors. The precursors are usually built up in the actual synthesis with the C10 indole chromophore attached from the beginning and with stepwise modification of the alicyclic portion of the molecule later on. An example of this kind of approach is illustrated in Scheme 14 (43). 3(R)-Vobasinediol (58) is... 

S), 15(R), and 16(S) (Scheme 19). Consequently, the problem regarding the transformation of 73 to 18 appears to involve simply the formation of the key C-7—C-20 bond from the rear side to construct rings C and E of 18 with the correct stereochemistry and the simultaneous conversion of the ethylidene side chain and the indole chromophore of 73 to the vinyl and the... 

The indole chromophore of tryptophan is the most important tool in studies of intrinsic protein fluorescence. The position of the maximum in the tryptophan fluorescence spectra recorded for proteins varies widely, from 308 nm for azurin to 350-353 nm for peptides lacking an ordered structure and for denatured proteins. (1) This is because of an important property of the fluorescence spectra of tryptophan residues, namely, their high sensitivity to interactions with the environment. Among extrinsic fluorescence probes, aminonaphthalene sulfonates are the most similar to tryptophan in this respect, which accounts for their wide application in protein research.(5)... 

The three aromatic amino acids (Phe, Tyr, Trp) have side-chain groups corresponding to the benzene, phenol, and indole chromophores, respectively. The spectroscopic properties of the rat transitions in these chromophores have been reviewed.136-381 Coupling of aromatic transitions among themselves and with peptide transitions can give rise to CD bands in the near and far (k < 250 nm) UV. Near-UV CD bands are useful indicators of the environment of the aromatic chromophores and can frequently be assigned to specific types of side chain, based upon band position, presence of vibrational fine structure, etc. Far-UV CD bands due to aromatic side chains, except for the La band of Tyr (-230 nm) and the Bb band of Trp (-225 nm), are generally difficult to resolve from peptide CD bands and can complicate the conformational analysis of peptides. 

However, the UV-spectrum of tetrahydroalstonine (maxima at 230 and 290 mp, inflection at 250 mp) indicates that it is composed of an indole chromophore plus additional absorption in the 250 mp region. This spectrum shows quite different characteristics from the summation spectrum of 2,3-dimethylindole and 2,6-dimethyl-3-carbomethoxy-5,6-dihydro-l,2-pyran (VII) the summation spectrum exhibits a pronounced minimum at 250 mp. Hence, formula VI for tetrahydroalstonine... 

The intramolecular singlet energy transfer from the phenol to the Indole chromophore in system [14] has been studied by Tamakl (55). 

The total emission spectra of these compounds, consisted only of those from the Indole chromophore neither the fluorescence, nor the phosphorescence of the phenol chromophore contributed to them. From the distortion of the absorption spectra can be concluded that a weak intramolecular hydrogen bonding of the indole chromophore to the phenolic oxygen or the tt orbitals of the phenol ring exists. The low fluorescence yields of compounds [14b] and [14c] were attributed to the formation of an Intramolecular complex between the Indole group in the excited state and the phenol group in the ground state. 

Plants of the G. multiflora group do not contain gardnerine (1) or its derivatives, which are characterized by their typical indole chromophore. The main constituent, gardneramine (4), and various accompanying alkaloids are all at the oxidation level of oxindole. As shown in Table HI, thirteen monomeric and two dimeric Gardneria alkaloids have been isolated, and most of the structures were elucidated through chemical correlation with the established structure of 4 165,166,169,172). 

Tabernaemontana divaricata (double flower variety) provided an unusual minor alkaloid, voaharine (178), whose structure was established by X-ray analysis [137]. Voaharine is exceptional in being in all probability a tryptamine and jccologanine derived alkaloid but possessing a 3-quinolone instead of an indole chromophore. Voaharine is probably derived from voaphylline (180) (which is also present in the plant) via oxidation and rearrangement and represents the first instance of a 3-quinolone-type alkaloid obtained from Tabernaemontana. Besides these, and the known alkaloids N-methylvoaphylline (181), pachysiphine (tabersonine-P-epoxide) and apparicine, as well as two new bisindoles (vide infra), the plant also provided several new alkaloids of the aspidosperma-type including (-)-mehranine (179), voafinine (182), N-methylvoafinine (183), voafinidine (184) and voalenine (185) which were obtained in minute amounts [138-140]. 

An elegant photochemical formation of an aryl-carbon bond through a PET mechanism was recently reported in the total synthesis of the potent antimitotic polycycle (-)-diazonamide A. The reaction was initiated by intramolecular electron transfer between the indole chromophore and the adjacent bromoarene (Scheme 2.10). Thus, compound 21 was treated with an aqueous-acetonitrile solution of LiOH and the resulting lithium phenoxide solution was degassed and photolyzed (Rayonet, 300 nm) to yield biaryl 22 (as a single atropodiastereomer) in a good yield. A radical-radical anion pair (23) was formed upon excitation, and... 

An important landmark in the elucidation of the structure of vinblastine (169), C46H58O9N4, was the discovery that the i.r. spectrum was largely super-imposable on the addition spectrum of two monomeric Vinca alkaloids, namely vindoline (171) and catharanthine (172). The structures of these two alkaloids, vindoline with a 6-methoxyindoline chromophore, catharanthine with an indole chromophore unsubstituted on nitrogen, were at that time unknown. 

The UV spectrum of roxburghine-D is not the simple summation of two independent indole chromophores since it exhibits additional absorption at 290 nm. Because an unsaturated carbonyl group is known to be present an attempt was made to hydrogenate the double bond or to reduce it by means of zinc and acetic acid but only very low yields of a reduction product could be obtained. The product, however, exhibited a typical indole spectrum and subtraction of the spectrum of this product from that of roxburghine-D gave a chromophore having Ajnax 290 nm (e 25,500) which could be explained only by the presence of... 

The second component of the macralstonine molecule, which contains the tautomeric hydroxyketone grouping, possesses a simple indole chromophore this was readily deduced from the UV spectrum of macralstonine which, after substraction of the spectrum of alstophylline, gave a curve identical with that expected for a simple indole derivative. Evidently the chromophores present in macralstonine are not conjugated. 

Okaramine Q (18) had a molecular formula of C32H32N4O4. The UV spectrum (Xmax 234, 288, 376 nm) indicated the presence of an indole chromophore with an expanded conjugation. The H-NMR spectrum of 18 resembled that of okaramine B (2), except for the absence of the methoxyl proton signal in 2 and the presence of signals due to isolated methylene protons. A precise comparison between the NMR spectra of 18 and 2 led to the conclusion that 18 is a demethoxyl derivative of 2 [23]. 

A substantial literature exists describing experimental and theoretical studies of the photophysical processes of indoles. In part, this reflects the well-established use of the magnitude of the Stokes shift seen in fluorescence spectrum of the indole chromophore to probe the local environment of tryptophan residues in biological molecules [4]. However, it also reflects the complexity of indole photophysics and the fact that some aspects remain controversial. Only an overview is presented here, because a proper discussion of the photophysics of the indole ring would easily fill this chapter. Unfortunately, no recent, comprehensive review of the topic is available however, early publications have been summarized [4,5], and recent papers in this area provide leading references and excellent brief reviews of subsequent work [6]. 

The tertiary alkaloid pleiocarpamine, C20H22N2O2 (mp 159°), was first isolated 2) from the roots of Pleiocarpa mutica Benth. and subsequently (3) from the bark of Hunteria eburnea Pichon (both Apocynaceae). It possesses (2) an A-substituted indole chromophore and its IR-spectrum indicated the presence of a carbonyl group (1727 cm i in Nujol or KBr) OH and NH absorptions were absent. Analysis revealed the presence of one methoxyl and one C-methyl group and the absence of A-methyl groups. 

Reduction of pleiocarpamine with lithium aluminum hydride gave the crystalline base pleiocarpaminol, C19H22N2O (mp 187°-189° Mn +114°, 0 = 0.266 in methanol), also with an A-substituted indole chromophore but showing hydroxyl absorption (3584 cm i) and no carbonyl absorption in the IR-spectrum. Pleiocarpamine was thus assumed to have a methoxycarbonyl group and pleiocarpaminol therefore contains a primary hydroxyl group (I). 

The proton-decoupled 13C NMR spectrum of pergolide mesylate indicates the presence of twenty carbons, which are further identified as four non-protonated carbons, six methine carbons, and ten methyl and methylene carbons via a Distortionless Enhancement by Polarization Transfer (DEPT) spectrum. The eight aromatic and olefinic carbon resonances in the 134 ppm to 106 ppm region have chemical shifts consistent with an indole structure (2). The H NMR spectrum contains four aromatic proton resonances, from 6.88 to 7.22 ppm, whose chemical shifts are also indicative of an indole-type structure. The assignment of these carbon and proton resonances were confirmed with IH correlation spectroscopy (CDSY) and 3C-1H heteronuclear correlation spectroscopy (HETCORR). The UV spectrum also indicates the presence of an indole chromophore. 

The UV absorption spectrum of pergolide mesylate is omsistent with the absorption pattern for compounds with an indole chromophore. The electronic transition of the indole chromophore of the pergolide mesylate molecule is observed as follows the absorption bands at 280 and 274 nm are... 

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