Lipase-catalyzed protection of the hydroxy groups of the nucleosides inosine and 2'-deoxyinosine: A new chemoenzymatic synthesis of the antiviral drug 2',3'-dideoxyinosine

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 11, 1999, Pages 1577-1582

  Ciuffreda, Pierangela ^a   Casati, Silvana ^a   Santaniello, Enzo ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; DEOXYINOSINE; DIDANOSINE; HYDROXYL GROUP; INOSINE; ORGANIC SOLVENT; TRIACYLGLYCEROL LIPASE;

ACYLATION; ARTICLE; CANDIDA; CATALYSIS; DRUG SYNTHESIS; ENZYME MECHANISM; HYDROLYSIS; PSEUDOMONAS;

ACYLATION; ANTI-HIV AGENTS; CANDIDA; DIDANOSINE; INOSINE; LIPASE; MODELS, CHEMICAL; PSEUDOMONAS;

CANDIDA; CANDIDA ANTARCTICA; PSEUDOMONAS; PSEUDOMONAS SP.;

EID: 0033532651     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00228-0     Document Type: Article

References (18)

1. Nasr, M.; Litterst, C.; McGowan, J. Antiviral Res. 1990, 14, 125.
2. DeClercq, E. AIDS Res. Human Retroviruses 1992, 8, 119.
3. Shelton, M. J.; O'Donnell, A. M.; Morse, G. D. Annals Of Pharmacotherapy 1992, 26, 660.
4. Bhat, V.; Stocker, E.; Ugarkar, B. G. Synth. Commun. 1992, 22, 1481.
5. Chu, C. K.; Bhadti, V. S.; Doboszewski, B.; Gu, Z. P.; Kosugi, Y.; Pullaiah, K. C.; Van Roey, P. J. Org. Chem. 1989, 54, 2217.
6. The experimental conditions were as reported: Griffin, B. E.; Jarman, M.; Reese, C. B.; Sulston, J. E. Tetrahedron, 1967, 23, 2301. We tried to carry out the reaction using trimethylorthoformate as reagent and solvent, but inosine 1a was insoluble in this reaction medium and compound 2a was formed in very poor yield; addition of dimethylsulfoxide did not improve the yields and complicated the work-up.
7. Shiragami, H.; Irie, Y.; Shirae, H.; Yokozeki, K.; Yasuda, N. J. Org. Chem. 1988, 53, 5170.
8. For a recent review see: Prasad, A. K.; Wengel, J. Nucleosides & Nucleotides 1996, 15, 1347.
9. The lipase used were obtained as follows: from Pseudomonas sp. (Lipase PS, Amano Pharmaceutical Co.), from Candida antarctica and Mucor miehei (Novo Nordisk), from Candida rugosa and porcine pancreas (Sigma).
10. (a) Degueil-Castaing, M.; De Jeso, B.; Drouillaid, S.; Maillard, B. Tetrahedron Lett. 1987, 28, 953. (b) Wang, Y.-F.; Lalonde, J. J.; Momongan, M.; Bergbreiter, D. E.; Wong, C.-H. J. Am. Chem. Soc. 1988, 110, 7200.
11. (a) Degueil-Castaing, M.; De Jeso, B.; Drouillaid, S.; Maillard, B. Tetrahedron Lett. 1987, 28, 953. (b) Wang, Y.-F.; Lalonde, J. J.; Momongan, M.; Bergbreiter, D. E.; Wong, C.-H. J. Am. Chem. Soc. 1988, 110, 7200.
12. Koskinen, A. M. P.; Klibanov, A.M., In Enzymatic Reactions in Organic Media; Chapman & Hall: London, 1996.
13. 2-MeOH 9:1). The reaction of 1a, lipase PS in DMSO (or DMF) was carried out with addition of enzyme (200 mg) each day. DMSO was removed by lyophilization.
14. 3) for the 2′ (23%).
15. 2-MeOH, 9:1) affording 7 and 5b (80 and 84% respectively). Alternatively, to compounds 6a or 6b (1.2 mmol) in water-saturated chloroform (10 ml) 1 g of CAL was added. The mixture was stirred at room temperature (48 h for both 6a and 6b) affording, after usual work-up, compounds 7 and 5b in comparable yields
16. The experimental procedure was in accord to the condition reported by Robbins, M. J.; Wilson, J. S.; Hansske, F. J. Am. Chem. Soc. 1983, 105, 4059.
17. 3).
18. 3-MeOH, 4:1) and was complete in 1h. The solution was lyophilized and the residue recrystallized from methanol to give 0.95 g (95%) of 2′-deoxyinosine 1b, spectroscopically identical to an authentic sample.