Stereoselektive Synthese von (2S,6S)‐2,6‐Diaminoheptandisäure und von unsymmetrischen Derivaten der meso‐2,6‐Diaminoheptandisäure

Abstract

Stereoselective Synthesis of (2S,6S)‐2,6‐Diaminoheptanedioic Acid and of Unsymmetrical Derivatives of meso‐2,6‐Diaminoheptanedioic AcidSpecific inhibition of enzymes of the diaminopimelate pathway (L‐lysine biosynthesis) should, in principle, lead to selective antibacterial agents or herbicides. For this purpose, enantioselective syntheses were devised for (2S, 6S)‐2, 6‐diaminoheptanedioic acid (L, L‐diaminopimelate, 1), (2R,6S)‐2,6‐diamino‐2‐methylhept‐3‐enedioic acid (10), (2R, 6S)‐2, 6‐diaminohept‐3‐enedioic acid (9), (2R, 6S)‐2, 6‐diamino‐4‐fluorohept‐3‐enedioic acid (42), and (2S, 6S)‐2, 6‐diamino‐3‐chloroheptanedioic acid (5). The Schöllkopf bislactim‐ether methodology was applied to control the configuration of C(2) and C(6) of 1, C(2) of 10, as well as C(6) of 9 and 42. Semialdehyde derivatives of L‐glutamate afforded C(6) of 10 and 5, while the (R)‐configurated C(2) of 9 and 42 were derived from L‐serine. For this purpose, the synthesis of the Garner aldehyde 32 has been improved. As chromatographic purifications and the low temperatures for the reduction of the carboxylic acid are eliminated, this valuable intermediate can now be prepared in bulk quantities. An enantio‐ and diastereoselective aldol addition of a glycine titanium‐enolate was applied for the construction of 5 (C(2) and C(3)). As all chiral building blocks and reagents used are available in both enantiomeric forms, these routes should also be suitable for the selective synthesis of the other stereoisomers of these bis(α‐amino acids).