Enantiospecific synthesis of (R)-2-carboxy-4-(3-phosphonopropyl)-piperazine [(R)-CPP] and (S)-3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid [(S)-Anap] via an improved strategy: Ring opening of chiral aziridine

Abstract

The chirality of CPP, a prominent N-methyl-d-aspartate (NMDA) antagonist, and Anap, a notable genetically encoded fluorescent unnatural amino acid, have a significantly influence on their biological activities. Enantiospecific synthesis of CPP and Anap has been achieved through an improved strategy of ring opening of chiral aziridine, accomplished in 6 steps with a total yield of 50 % for CPP and in 4 steps with a total yield of 59 % for Anap. This unified method significantly shortened the synthetic process, improved overall yield, and demonstrated the potential for industrial-scale development.