An Alternative Synthesis of the Enantiomerically Pure Competitive NMIDA Antagonists SDZ 220‐581 and SDZ EAB 515

Abstract

An alternative synthesis of enantiomerically pure SDZ 220-881 (la) and SDZ EAB 515 (lb) starting from L-Z-tyrosine is described.Introduction. -Biphenyl analogues of AP7 ((2R)-2-amino-7-phosphonoheptanoic acid) such as SDZ 220-581 (la) and SDZ EAB 515 (lb) are selective competitive NMDA antagonists with high affinities for the NMDA recognition site in vitro [1][2] and with corresponding in vivo activities in various animal models [3]. Recently [I], we published a synthesis of enantiomerically pure SDZ EAB 51 5 (lb) and its substituted analogues by employing the chiral glycine derivative 3 (Scheme 1) [4]. We describe here an alternative synthesis of such compounds by starting from the readily available L-Z-tyrosine.

Intensified biocatalytic production of enantiomerically pure halophenylalanines from acrylic acids using ammonium carbamate as the ammonia source

“…The crude product obtained after removal of ammonium carbamate by sublimation could be used without further treatment for N-protection followed by Suzuki-Miyaura coupling, 4 affording 4 in 24% overall isolated yield from 1j (Scheme 2). The structural moiety of 3-aryl substituted phenylalanine is present in several pharmaceutical ingredients and building blocks, such as selective N-methyl-D-aspartate receptor (NMDA) antagonists for treatment of Parkinson's disease, 20,21 angiotensinconverting enzyme 2 (ACE-2) modulators for weight disorders 22 and chemotactic peptides. 23 In conclusion, an improved and simplified method for the production of various halogenated amino acids in excellent enantiomeric excess has been reported.…”