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.
Kesel
Andreas J
AJ
Chammünsterstrasse 47, D-81827 München, Germany. andreas.kesel@t-online.de
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000737:chemistry; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011736:Pyridoxine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D012176:Retinoids / Q000737:chemistry*; D012236:Rhodanine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013053:Spectrophotometry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000737:chemistry; D014801:Vitamin A / Q000737:chemistry*; D025101:Vitamin B 6 / Q000737:chemistry*
C471041:2',3O-retinylidyne-5'-O-phosphonopyridoxylidenerhodanine; C471040:5'-O-phosphonopyridoxylidenerhodanine; D019380:Anti-HIV Agents; D015696:Gene Products, tat; D046911:Macromolecular Substances; D012176:Retinoids; D014801:Vitamin A; D014212:Tretinoin; D012236:Rhodanine; D025101:Vitamin B 6; D011736:Pyridoxine