Indoles hydroxylation

Li, Q.-S., Schwaneberg, U., Fischer, P., Schmid, R.D. (2000), Directed evolution of the fatty acid hydroxylase P450 BM-3 into an indole-hydroxylating catalyst, Chem. Eur.J. 6, 1531-1536. 

The conversion of indoles to oxindoles can be achieved in several ways. Reaction of indoles with a halogenaling agent such as NCS, NBS or pyridin-ium bromide perbromide in hydroxylic solvents leads to oxindoles[l]. The reaction proceeds by nucleophilic addition to a 3-haloindolenium intermediate. 

Rauwolscine gives colour reactions like those of yohimbine and the absorption curves of the hydrochlorides of the two alkaloids are very similar. Heated to 300°/5 mm. rauwolscinic acid forms barman (p. 490) and 3-ethylindole and on fusion with potassium hydroxide decomposes into indole-2-carboxylic acid, isophthalic acid, barman and an unidentified indole derivative. Rauwolscine itself on distillation with zinc dust produces barman, 2-methylindole (scatole) and tsoquinoline. It is suggested that the alkaloid has the skeletal strueture suggested by Seholz (formula XIV, p. 508) for yohimbine, the positions of the hydroxyl and earbomethoxy grouf s being still imdetermined. 

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

When the German ending -ol does not indicate hydroxyl it should be translated -ole (as, anisole, indole), or in the case of a few hydrocarbons -ene (as. Benzol, benzene Toluol, toluene Styrol, styrene). 

Indene, 6, 7-dimethox y-3-meti iy l-2 -CARBETHOXY-, 40, 43 Indene, hydroxylation of, 41, 53 Indole, methylation to 1-methylindole, 40,68... 

Hartman RE et al. (1964) Microbial hydroxylation of indole alkaloids. Appl Microbiol 12 138-140... 

Methyl-substituted indole has been the subject of an investigation and the degradation metabolites were identified [346], An indole-degrading methanogenic consortium induced a two-step reaction on 3-methylindole, through a hydroxylation pathway that... 

The functional groups of the enzyme involved in the chemical bonding are the TV-terminal and s-amino groups (from lysine) as well as the carboxy-(aspartic or glutamic acid), sulfhydryl- (cysteine), hydroxyl- (serine, threonine), indole (tryptophan), imidazole (hystidine) and phenolic (tyrosine) functions. 

In the context of Pmp-containing tripeptide derivatives, the 3-indol-l-yl-pro-pyl analogue turned out to exhibit high affinity. Substituting the indol 5-posi-tion with methyl or hydroxyl resulted in compounds 41 and 42 with subnanomolar IC50 values (Scheme 7). These have been the first compounds of SH2 domain antagonists with subnanomolar affinity reported. These systematic studies enabled Novartis to push further analogues into in vivo studies [148,... 

Microbial transformations of four heteroyohimbine stereoisomers [ajmalicine (81a) tetrahydroalstonine (81b), isoajmalicine (81c), and akumigine (81d)] yielded mixtures of 10- and 11-hydroxylation products (786) (Scheme 21). Microorganisms known for their abilities to metabolize indole alkaloids, steroids, and antibiotics were intitially screened, and seven cultures were further used for preparative-scale incubations with alkaloid substrate. The microorganisms used and yields (by HPLC) of metabolites obtained from 81a-81d are shown in Table HI. 

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