Large Scale Synthesis of Mono- and Di-urethane Derivatives of Lysine.

Orthogonally protected diurethane derivatives of lysine are valuable materials for peptide syntheses. An example is ZLys(Boc), which is exploited in the industrial production of certain well-established peptide drugs. 3,4) Another derivative is Fmoc-Lys(Boc), which is in common use in the laboratory synthesis of peptides. 5) The simplest route to these lysine derivatives seems to be using the copper complex for simultaneous protection of the a-amino and a-carboxyl function, N e -tert-butoxycarbonylation and then copper detachment. The obtained Lys(Boc) might be then subjected to N a -benzyloxycarbonylation.

AN IMPROVED SYNTHESIS OFNα-BENZYLOXYCARBONYL-L-LYSINE

Improved scalable syntheses of mono- and bis-urethane derivatives of ornithine.

In the search for a practical route to ornithine bisurethane derivatives useful for peptide synthesis, we elaborated the simple and efficient (86% yield) synthesis of N(epsilon)-tert-butoxycarbonyl-L-ornithine copper(II) complex (1). This served as substrate for obtaining N(epsilon)-tert-butoxycarbonyl-L-ornithine (2), N(alpha)-benzyloxycarbonyl-N(epsilon)-tert-butoxycarbonyl-L-ornithine (3) and N(alpha)-(9-fluorenyl)methoxycarbonyl-N(epsilon)-tert-butoxycarbonyl-L-ornithine (4). These were synthesized in 94-95% yields and with a purity above 99%.

SCALABLE SYNTHESES OFNα-BENZYLOXYCARBONYL-l-ORNITHINE AND OFNα-(9-FLUORENYLMETHOXY)CARBONYL-l-ORNITHINEE

(2002). SCALABLE SYNTHESES OF N α-BENZYLOXYCARBONYL-l-ORNITHINE AND OF N α-(9-FLUORENYLMETHOXY)CARBONYL-l-ORNITHINEE. Organic Preparations and Procedures International: Vol. 34, No. 5, pp. 531-537.