O-Methyltyrosine

CF3SO3H, PhSMe, 0-25°. ° In this case O-methyltyrosine was depro-tected without evidence for O C migration, which is often a problem when removing protective groups from tyrosine. 

Fluororesorcinol can be prepared from derivatives of resorcinol and fluo-roxytrifluoromethane [15, 24] (equation 4) or by fluorination of resorcinol with cesium fluoroxysulfate [25] (equation 5). Reaction of acetyl hypofluorite with M-acetyl-O-methyltyrosine methyl ester provides a good route to 3-fluorotyrosine derivatives [26] (equation 6). 

In testing the possibility of proton transfer as a quenching mechanism of tyrosine in oligopeptide/polynucleotide complexes, Brun et a/.(102) compared the fluorescence emission spectra of the tyrosine and O-methyltyrosine tripeptides. They noted that, in the complex, the O-methyltyrosine tripeptide had a unique secondary emission near 410 nm. Whether this emission is related to that observed by Libertini and Small(94) is an important question. While one must consider the possibility that two tyrosine side chains could be converted to dityrosine, (96) which has a fluorescence at 400 nm, another intriguing possibility is ambient temperature tyrosine phosphorescence. This could happen if the tyrosine side chain is in a rigid, protective environment, very effectively shielded from collisions with quenchers, particularly oxygen. 

Deprotection of O-methyltyrosine. O-Methylation of tyrosine (1) has represented an irreversible protection of the phenol group, since cleavage is accomplished only under drastic conditions. A new, mild method for deprotection involves treatment of 1 with thioanisole and trifluoromethanesulfonic acid in trifiuoroacetic acid. This method was used in the final step of a synthesis of a pentapeptide (43%... 

Fig. 5.1 8 Positive selection for picking up TyrRS mutants that aminoacylate the orthogonal tRNA with O-methyltyrosine.

The starting materials for the synthesis were the known methyl (S)-O-methyltyrosine and the protected aminoaldehyde 45, which was prepared following the multi-step sequence depicted in Scheme 19 (69% yield from the known amino ester intermediate). The protecting group of choice was the Fukuyama-type nitrosulfonamide [35], readily cleavable but stable in the oxidative-cyclization reaction. 

In summary, Sorensen completed a concise synthesis of FR901483 (16 steps from methyl ester of O-methyltyrosine, 1.5% overall yield) by a strategy that for the first time featured an oxidative cyclization of a phenolic secondary amine (obtained by a reductive coupling of two tyrosine units). The other notable aspect of his synthesis is the one-step conversion of a hydroxyl group to a phosphate unit with an inversion of configuration that shortens the global sequence in comparison with other routes. 

Apratoxin A, a 25-membered cydodep-sipeptide - depsipeptides) isolated from the marine cyanobacterium Lyngbya majuscule, and exhibiting potent cytotoxic activity. Apratoxin A consists of a proline, three methylated amino acids (N-methylisoleucine, N-methylalanine, O-methyltyrosine), an a,-unsaturated modified cysteine residue (moCys) and a dihy-droxylated fatty acid moiety, 3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid (Dtena) [H. Luesdi et al., J. Am. Chem. Soc. 2001, 123, 5418 H. Luesch et al.,/. Bioorg. Med. Chem. 2002,10,1973 J. Chen, C. J. Forsyth, Proc. Nall. Acad. Sci. USA 2004,101,12067 ... 

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