Indole 2-thioether

Ox indole-derivatives. Hydrolysis of an indole 2-thioether in 20% acetic acid at 95-120° C in a sealed tube gives the corresponding oxindole. The reaction was studied with several indole 2-thioethers, the results of this study (420) can be summarized as follows. Various 2-sulfenyl... 

Oxidation. Oxidation of an indole 2-thioether is of interest since this would increase the number of derivatives of tryptophan obtainable from the sulfenylation reaction, thus providing new permutations in the study of the structure-function relationships of tryptophan-containing peptides and proteins. In addition, the indole 2-sulfoxide function occurs naturally in the poisonous cyclic peptides amatoxins 114, 429). 

WiELAND and CO workers 64, 114, 429) independently reported oxidation of the indole-2-thioether function with H2O2 in acetic acid and applied the oxidative reaction to phalloidin. The isolation of the... 

The formation of indole thioethers can be carried out at C-4 by a process involving migration from C-3. An intramolecular acylation of 2-(3-indolylthio)propionic acid undergoes reaction at C-3, with rearrangement of the sidfur moiety and substitution at C-4 via a sulfenyl chloride there is also good optical retention in a chiral substrate (Scheme 51) <92TL47I7>. 

WiELAND, Th., C. Jochum, and H. Faulstich Optimization of the Synthesis of 2-Indole Thioethers from Derivatives of Tryptophan and Cysteine. Liebigs Ann. Chem. 727, 138-142 (1969). 

Rainier devised a variant of the 5-exo-dig radical cyclization of 2-alkynylisocyanides 122 wherein thiols were utilized to both initiate the radical cascade as well as act as nucleophiles in the reaction with the indolenine intermediate 123 yielding the indoles 124 . When R = TMS, elimination of the C-10 thioether can be effected in a gramine-like fashion so as to add nucleophiles (e.g., malonate anion) in the presence of Bu3P allowing for the preparation of more highly functionalized indoles. 

Intramolecular cyclization of 2-lithiobenzyl-2-halophenyl amines, ethers, and thioethers—Synthesis of phenanthridine, dibenzopyran, and dibenzothiopyran derivatives Having demonstrated the efficiency of this methodology for the preparation of indole derivatives, we prepared the 2-fluoro-phenyl ether and thioether 22 a, b to study their potential as substrates that could afford oxygen and sulfur heterocycles. However, treatment of 22 a, b with fBuLi afforded, after... 

The major metal-binding amino acid side chains in proteins (Gurd and Wilcox, 1956 see Voet and Voet, 1990) (Table II) are carboxyl (aspartic acid and glutamic acid), imidazole (histidine), indole (tryptophan), thiol (cysteine), thioether (methionine), hydroxyl (serine, threonine, and tyrosine), and possibly amide groups (asparagine and glutamine, although... 

In contrast to the 5-endo-trig anionic cyclization reactions, rarely observed, there are several examples in which 5-endo-dig processes are involved. Hence 2,3-disubstituted benzofurans, benzothiophenes and indoles 374 have been synthesized starting from triflu-oroethyl ethers, thioethers and anilines 373, respectively, and alkyllithium compounds. A 5-endo-dig carbolithiation reaction on 375, generated by two successive eliminations, one substitution and one ortho-lithiation reactions, is proposed to account for the formation of the corresponding 2-lithiated heterocycles. Further reaction of these intermediates with electrophiles affords compounds 374 (Scheme 98)159. In the case of thioether 373 (X = S) a bromine substituent must be present at the ortho position. 

Approximately 150 different amino acid residues have been reported in proteins (1 5). At least half of these could undergo chemical deteriorations under the conditions of stress usually encountered. Many of these deteriorative reactions involve hydrolytic scissions, not only of peptide bonds but of the many different nonprotein substances added covalently to proteins postribosomally. These susceptible side chain groups are indole, phenoxy, thioether, amino, imidazole, sulfhydryl, and derivatives of serine and threonine (such as 0-glycosyl or O-phosphoryl), the disulfides of cystine, and, of course, the amides (such as asparagine and glutamine). With strong acid or alkali, other residues, such as serine and threonine, also are less stable. 

In reducing conditions, alkylation of amino, indole, thiol, and thioether groups, and binding of saccharides to a.a. residues are possible ... 

---