Synthesis of beta- and gamma-fluorenylmethyl esters of respectively N alpha-Boc-L-aspartic acid and N alpha-Boc-L-glutamic acid.
The orthogonal synthesis of N alpha-Boc-L-aspartic acid-gamma-fluorenylmethyl ester and N alpha-Boc-L-glutamic acid-delta-fluorenylmethyl ester is reported. This is a four-step synthesis that relies on the selective esterification of the side-chain carboxyl groups on N alpha-CBZ-L-aspartic acid and N alpha-CBZ-L-glutamic acid. Such selectivity is accomplished by initially protecting the alpha-carboxyl group through the formation of the corresponding 5-oxo-4-oxazolidinone ring. Following side-chain esterification, the alpha-carboxyl and alpha-amino groups are deprotected with acidolysis. Finally, the alpha-amino group is reprotected with the t-butyl-oxycarbonyl (Boc) group. Thus aspartic acid and glutamic acid have their side-chain carboxyl groups protected with the base-labile fluorenylmethyl ester (OFm) and their alpha-amino groups protected with the acid-labile Boc group. These residues, when used in conjunction with N alpha-Boc-N epsilon-Fmoc-L-lysine, are important in the formation of side-chain to side-chain cyclizations, via an amide bridge, during solid-phase peptide synthesis.
al-Obeidi
F
F
Department of Chemistry, University of Arizona, Tucson.
Sanderson
D G
DG
Hruby
V J
VJ
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D002855:Chromatography, Thin Layer; D004951:Esterification; D005449:Fluorenes / Q000138:chemical synthesis*; D005971:Glutamates / Q000138:chemical synthesis*; D018698:Glutamic Acid; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared
D005449:Fluorenes; D005971:Glutamates; C064373:N-alpha-tert-butyloxycarbonyl-aspartic acid gamma-fluorenylmethyl ester; C064374:N-alpha-tert-butyloxycarbonylglutamic acid gamma-fluorenylmethyl ester; C064372:N-alpha-tert-butyloxycarbonylaspartic acid beta-fluorenylmethyl ester; C064375:N-alpha-tert-butyloxycarbonyl-glutamic acid beta-fluorenylmethyl ester; D001224:Aspartic Acid; D018698:Glutamic Acid