al-Obeidi F, Sanderson D G, Hruby V J
Department of Chemistry, University of Arizona, Tucson.
Int J Pept Protein Res. 1990 Mar;35(3):215-8.
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.
报道了Nα -叔丁氧羰基 -L -天冬氨酸 -γ -芴甲氧酯和Nα -叔丁氧羰基 -L -谷氨酸 -δ -芴甲氧酯的正交合成。这是一个四步合成法，依赖于Nα -苄氧羰基 -L -天冬氨酸和Nα -苄氧羰基 -L -谷氨酸侧链羧基的选择性酯化。这种选择性是通过首先通过形成相应的5 -氧代 -4 -恶唑烷酮环来保护α -羧基来实现的。在侧链酯化之后，通过酸解使α -羧基和α -氨基脱保护。最后，用叔丁氧羰基（Boc）基团重新保护α -氨基。因此，天冬氨酸和谷氨酸的侧链羧基用对碱不稳定的芴甲氧酯（OFm）保护，它们的α -氨基用对酸不稳定의Boc基团保护。在固相肽合成过程中，当这些残基与Nα -叔丁氧羰基 -Nε -芴甲氧羰基 -L -赖氨酸一起使用时，对于通过酰胺桥形成侧链到侧链的环化很重要。
