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.

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. Based on the improved strategy of ring opening of chiral aziridine, enantiospecific synthesis of N -methyI- d -aspartate antagonist (R)-2-carboxy-4-(3-phosphonopropyl)piperazine [(R)-CPP] and genetically encoded fluorescent unnatural amino acid (S)-3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid [(S)-Anap] has been accomplished. This unified synthetic method has notably reduced the synthetic steps and improved the total yield in contrast with previous methodologies. [Display omitted] • (R)-CPP and (S)-Anap have been enantiospecifically synthesized based on ring opening of chiral aziridine. • More optimized process route has been accomplished. • This synthetic strategy has high yield and scalability. [ABSTRACT FROM AUTHOR]