Biochemical and Biophysical Research Communications, Vol.300, No.3, 793-799, 2003
Synthesis of retinoid vitamin A vitamin B-6 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 traps-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-traps 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 (H-1-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. (C) 2002 Elsevier Science (USA). All rights reserved.