Synthesis of retinoid vitamin A-vitamin B6 conjugate analogues for antiviral chemotherapy.

The synthesis of retinoid vitamin A-vitamin B(6) conjugate analogues from a vitamin B(6) coenzyme analogue and putative HIV-1 trans-activating transcriptional regulatory protein Tat antagonist (Z)-5(')-O-phosphono-pyridoxylidenerhodanine (B6PR) monosodium salt hemiheptadecahydrate [(Z)-B6PRNa8.5H(2)O] is discussed here. All-trans-retinoic acid (ATRA) is coupled to B6PR by a modified Stork enamine acylation. It results in a product library of more than eight compounds, each with at least one intact all-trans or 13-cis vitamin A double bond system. This yellow oily concentrate mixture was subjected to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry (MS), UV/VIS-spectrophotometry, and proton nuclear magnetic resonance spectroscopy (1H-NMR). The chemical structures of six components of the concentrate mixture could be established by combination of these analytical methods. The two main components are 65% 2(')C,3O-(all-trans-retinylidyne)B6PT (B6RA) and 25% 2(')C-(all-trans-retinoyl)B6PT, chemically derived from (5RS)-5-(5(')-O-phosphono-pyridoxyl)-2,4-thiazolidinedione (B6PT). This new retinoid selection could be of further interest in antiviral applications, especially treating conditions caused by RNA viruses like HIV.