Butyloxycarbonyl group, tert

A perfluoro-tagged tert-butyloxycarbonyl group ( Boc) has been used for the protection of primary amino functions in the synthesis of a small amide library [29]. The Boc-protected amino acids were coupled wifh primary or secondary amines. The products were purified by preparative fluorous HPLC. After deprotection by add treatment, the products were isolated by conventional extractive work-up. 

Chiral intermediates for the synthesis of (-)-anisomycin (1) and (+)-anisomycin (anti-1) (153), (R)-2-(p-methoxyphenyl)methyl-2,5-dihydro-pyrrole (142) and its (S)-isomer (+)-187, have been efficiently synthesized from D-tyrosine and L-tyrosine, respectively (Scheme 20) [28]. D-tyrosine was converted to 0-methyl D-tyrosine methyl ester (182) [72-75] which was treated with di-tert-butyl dicarbonate to protect the amino group. Subsequent reduction of the ester group with sodium borohydride in the presence of lithium chloride furnished the alcohol 183. Swern oxidation of 183 followed by chain extension with the anion derived from bis(2,2,2-trifluoroethyl)(ethoxycarbonylmethyl)-phosphonate afforded (Z)-Q ,/0-unsaturated ester (184), which was used immediately without purification to avoid or minimize any possible racemization of the chiral center. Reduction of the ester group of 184 with diisobutylaluminium hydride afforded the alcohol 185 which after mesylation followed by intramolecular cyclization gave the desired 2,5-dihydropyrrole derivative 186. Removal of the tert-butyloxycarbonyl group was achieved by treatment with trifuoroacetic acid to give (-)-142 in 62% overall yield from 182. The (S)-2,5-dihydropyrrole (-l-)-187 was also prepared in the same manner starting from L-tyrosine. Since (-l-)-187 had been transformed into (-l-)-anisomycin (anti-1) (153), (-)-142 could also be transformed to the (-)-anisomycin (1) [26,66]. 

Acylation of the SH function provides no unequivocal protection, because S-acyl groups can migrate to amino groups. This S - N acyl transfer is not too pronounced in blocking with the S-benzyloxycarbonyl or with the S-tert.butyloxycarbonyl groups, but these possibilities remain to be tested in practice. Somewhat wider application has been reported of the S-ethylcarba-moyl group... 

The picolyl ester group is quite resistant to acids, because protonation of the pyridine ring destabilizes the potential carbo-cation at the benzylic carbon atom. Hence, the tert.butyloxycarbonyl group, applied for the blocking of a-amino functions, can be selectively cleaved by trifluoroacetic acid and the resulting amine salt used in the following coupling step ... 

In analogy to the advantageous compatibility in conventional peptide chemistry of C-ter-minal benzyl esters with acid-labile N-protecting residues at least as sensitive as the tert. butyloxycarbonyl group, Merrifield anchored the amino acids onto polymer by benzyl ester type linkages (see p. 3). 

The r -alkoxycarbonyl residues, e. g., the tert-butyloxycarbonyl groups, are cleaved under acid-catalyzed conditions ... 

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