1. Synthesis of beta- and gamma-fluorenylmethyl esters of respectively N alpha-Boc-L-aspartic acid and N alpha-Boc-L-glutamic acid
F al-Obeidi, D G Sanderson, V J Hruby 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.
2. Synthesis and use of N, N-di-Boc-glutamate gamma-semialdehydes and related aldehydes
V Constantinou-Kokotou, V Magrioti Amino Acids. 2003 Apr;24(3):231-43. doi: 10.1007/s00726-002-0403-8.
This review article focuses on the synthesis and reactions of N, N-di-Boc glutamate and aspartate semialdehydes as well as related aldehydes. These building blocks are prepared according to various strategies from glutamic and aspartic acids and find interesting synthetic applications. In the first part, the methods for the synthesis of N, N-di-Boc-amino aldehydes are summarized. The applications of these chiral synthons for the synthesis of unnatural amino acids and other bioactive compounds are discussed in the second section.
3. Preparation of N-9-fluorenylmethoxycarbonylamino acid chlorides from mixed anhydrides by the action of hydrogen chloride
F M Chen, Y C Lee, N L Benoiton Int J Pept Protein Res. 1991 Aug;38(2):97-102. doi: 10.1111/j.1399-3011.1991.tb01416.x.
N-9-Fluorenylmethoxycarbonyl-(Fmoc) amino-acid chlorides have been prepared by reaction of hydrogen chloride on purified mixed Fmoc-amino acid-monoalkyl carbonic acid anhydrides in dichloromethane. The products partially undergo subsequent conversion to the corresponding esters due to the presence of the liberated alcohol, the extent depending on the nature of the alkyl group. Esterification occurred to 5-20% when the alkyl group was isopropyl. Anhydrides of monoisopropenyl carbonic acid which liberate acetone instead of an alcohol gave products uncontaminated with ester. The three components in a reaction mixture could be determined as the reaction progressed by normal phase high-performance liquid chromatography of aliquots, which had been freed of excess hydrogen chloride, on a mu Porasil (underivatized silica) column using tert.-butanol-hexane (1.5:98.5) as solvent.
