New approaches towards the synthesis of 1,2,3,4-tetrahydro isoquinoline-3-phosphonic acid (TicP)

• Published in: Amino acids Vol. 53; no. 3; pp. 451 - 459
• Main Authors: Viveros-Ceballos, José Luis, Matías-Valdez, Lizeth A., Sayago, Francisco J., Cativiela, Carlos, Ordóñez, Mario
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01-03-2021; Springer Nature B.V
• Subjects: Analytical Chemistry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Carboxylic acids; Decarboxylation; Life Sciences; Neurobiology; Original Article; Phosphonic acids; Phosphorylation; Proteomics; Synthesis; Tetrahydroisoquinoline; Phosphorylation; α-Aminophosphonic acids; α,β-Dehydroaminophosphonate; Wittig–Horner and Pictet–Spengler reactions; Acyliminium ion; Radical fragmentation; N-Acyliminium ion
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-021-02962-4

Two new strategies for the efficient synthesis of racemic 1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (Tic
P
) (±)-
2
have been developed. The first strategy involves the electron-transfer reduction of the easily obtained α,β-dehydro phosphonophenylalanine followed by a Pictet–Spengler cyclization. The second strategy involves a radical decarboxylation–phosphorylation reaction on 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). In both strategies, the highly electrophilic
N
-acyliminium ion is formed as a key intermediate, and the target compound is obtained in good yield using mild reaction conditions and readily available starting materials, complementing existing methodologies and contributing to the easy accessibility of (±)-
2
for further research.