Crystal structures indole

Fig. 8.10 The X-ray crystal structure of a tetracyclic compound bound to hepatitis C virus NS5B544 polymerase. The observed dihedral angle between the indole ring and phenyl ring is 47°, which is in agreement with the predictions.

The matter was settled in 1994 in back-to-back communications by Gould [12] and Dmitrienko [13]. Gould showed that treatment of natural prekinamycin with dirhodium tetraacetate in methanol yielded the fluorene 16 (Scheme 3.1). The vinyl proton formed in this reaction (H-l) provided a critical spectroscopic handle and allowed unambiguous determination of the carbocyclic structure, excluding the presence of an indole heterocycle. In parallel, his research group obtained a high-quality crystal structure of a kinamycin derivative. The refined data set was shown to best accommodate a diazo rather than cyanamide (or isonitrile) function. 

Fig. 10.7 Crystal structure of com pounds 4 stick representation of H-bond (dotted lines) superstructures of (A) phenyl, (B) indole, (C) phenol ureido-silsesquioxanes H atoms were omitted for clarity.

Figure 7. (a) Stereo view of comparison of the main chain of the X-ray structure of the HIV-1 protease complex with compound 2 (red) with the main chains of the minimized complex (yellow) and a 20ps average dynamical structure of the same complex of HIV-1 protease (green), (b) Stereoview of the active-site geometry of the crystal structure (in half-bond color) of the HIV-1 protease complexed with the compound 2 (with the indole and phenyl groups shown in red) as revealed by X-ray crystallography. 

X-ray structural data have identified the conformations responsible for receptor binding for a series of 6-arylpyrrolo[2,l-d][l,5]benzothiazepines (1995JMC4730). Crystal structures of methyl 12-methyl-12H-[3]benzoxepino-[l,2-l7]indole-5-carboxylate 135 (1996JCS(P1)1767), benzoxepino[4,3- 7]indole (1993AX(C)2126), and natural furobenzoxepine (1990JCR(S)114) have been reported. 

Varney MD, Marzoni GP, Palmer CL, Deal JG, Webber S, Welsh KM, Bacquet RJ, Bartlett CA, Morse CA, Booth CLJ, Herrmann SM, Howland EF, Ward RW, White J. Crystal-structure-based design of Benz[cd]indole-containing inhibitors of thymidylate synthase. JMed Chem 1992 35 663-676. 

Besides having a noncovalent association of subunits as in tryptophan synthase, some enzymes are double-headed, in that they contain two distinct activities in a single polypeptide chain. A good example of this is the indole 3-glycerol phosphate-synthase-phosphoribosyl anthranilate isomerase bifunc-tional enzyme from the tryptophan operon of E. coli. The crystal structure of the complex has been solved at 2.0 A resolution.39 The two enzymes have been separated by genetic manipulation.40 The activity of the two separate monomeric monofunctional constituents is the same as in the covalent complex so there is no catalytic advantage of having the proteins fused. 

Crystal structure data are available for an indole—trinitrobenzene complex (2) and for the lithium and sodium salts in the presence of polyamine ligands (3). The crystal structure of indole itself is evidently disordered (4). Table 1 gives the and C-nmr assignments in CDC13 (5). 13C-nmr assignments have been tabulated for many other indole derivatives (6). 

The crystal structure of pentathiepino [6,7- indole has been determined <1994TL5279>. X-Ray crystal structure analysis revealed that 4,5-ethylenedithio-4,5-pentathiotetrathiofulvalene <1999AM758> moiety has a bent structure resembling the molecular structure of neutral bis(ethylenedithio)tetrathiafulvalene and that the pentathio group adopts a chair-formed conformation. The intradimer interplane distance is 3.35 A, which is much shorter than the interdimer one (4.45 A). In a molecule, there are many intermolecular S-S contacts shorter than the sum of the van der Waals radii (3.7 A), and a two-dimensional network of sulfur atoms was developed between the pentathio groups and tetrathiafulvalene moieties. Furthermore, chlorobenzene molecules are beside the anion and occupy the void space as the interstitial solvent. They are also located on the mirror plane and are disordered at two positions with inversion symmetry because of the cavity structure of the void space. 

The potential for transition metal complexes to provide new reactivity patterns continues to be explored by the preparation of complexes and the study of their reactivity patterns. The aminoalkyl substituents of gramine, tryptamine and methyl tryptophanate promoted metalation at C2 of the indole ring by Pt(DMSO)2Cl2. The crystal structure of the gramine product was determined. 

The three-dimensional structure of the tryptophan synthase 02)82 complex from S. typhimurium reveals that the four polypeptide subunits are arranged in an extended a/8/Jo order forming a complex 150 A long.7 A schematic view of a single a/ ft pair based on the crystal structure is shown in the color plate . The 02)82 complex catalyzes the synthesis of L-tryptophan from indole-3-glycerol phosphate and L-serine, termed the a)3 reaction (Fig. 7.1). The a and )3 subunits can be separated and shown to catalyze two distinct reactions, termed the a and / reactions, respectively (Fig. 7.1). The rates of the a and / reactions are greatly increased when catalyzed by the 02)82 complex. Although the o)3 reaction is formally the sum of the a and )3 reactions, indole does not appear as a free intermediate in solution in this reaction.17-21 This result indicates that indole is a... 

The active sites of the a and /3 subunits are separated by 25-30 A and are connected by a tunnel of sufficient size to permit direct diffusion of indole between the heterologous active sites (Fig. 7.1).7) Fig. 7.1 shows our current picture of the mechanism of the a/3 reaction based on the crystal structure. The indole intermediate [IND] in Fig. 7.1, which is produced by cleavage of indole-3-glycerol phosphate at the a site, diffuses through an intramolecular tunnel to the / site where it undergoes a pyridoxal phosphate-dependent /3-replacement reaction with L-serine to form L-tryptophan. The catalytic mechanism of this reaction is described further in Section 7.7. 

Our group has also encountered success in cycloadding an isomiinchnone dipole across an indole double bond [28]. Cycloadduct 91 was generated in high yield as a single diastereomer from the Rh2(OAc)4-catalyzed reaction of diazoimide 90. The assignment was unequivocally established by an X-ray crystal structure. The ready construction of these poly-heterocycles in one step and in... 

Microwave spectroscopy is especially useful in the indole system where the crystal structure is composed of two different molecular orientations with different bond lengths and angles. The values given by microwave spectroscopy... 

A 10-step kinetic model has been developed (Santolini et al., 2001). Crystal structures of xyNOS show that a Tyr-409 indol nitrogen atom forms a strong hydrogen bond with the heme thiolate (Crane et al., 1988 Raman et al.1998 Fishmann et al., 1999). The Try-409 mutation suggests that the heme potential controls the NOS reactions (Adak et al. 2001). Suppression of this hydrogen bond through the mutation lowers the reduction potential of the heme, inhibits heme reduction and accelerates oxidation of the Fe(II) heme-NO complex. The Arg binding increases the reduction potential of the NOS heme. 

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