Abstract
A chemo-enzymatic synthesis of 9-(β-d -arabinofuranosyl)-2-fluoroadenine
(Fludarabine) and 9-(β-d -arabinofuranosyl)-2-amino-6-methoxypurine
(Nelarabine) using α-d -arabinofuranose 1-phosphate
as a universal substrate and recombinant E.
coli purine nucleoside phosphorylase (PNP) as a biocatalyst
is described. MacDonald’s method was employed for the synthesis
of α-d -arabinofuranose 1-phosphate,
which was prepared as a mixture with β-d -arabinopyranose
1-phosphate, starting from peracyl derivatives of d -arabinose
of different isomeric (anomeric) composition. It was found that
the mixed phosphates can be successfully used in the reaction with
purine base catalyzed by PNP pointing to the inertia of β-d -arabinopyranose 1-phosphate in regard
to PNP. Reaction of 2-fluoroadenine and α-d -arabinofuranose
1-phosphate is shifted towards the formation of Fludarabine, whereas
the reaction of 2-amino-6-methoxypurine reached equilibrium at a
ca. equimolar ratio of the base and Nelarabine. Recombinant E. coli uridine phosphorylase catalyzed
the synthesis of 1-(β-d -arabinofuranosyl)thymine (ara-T)
from thymine and α-d -arabinofuranose
1-phosphate.
Key words
α-d -arabinofuranose 1-phosphate - recombinant E.coli nucleoside phosphorylases - purine nucleosides - ara-T
References
1a Mikhailopulo IA.
Curr. Org. Chem.
2007,
11:
317
1b Mikhailopulo IA.
Miroshnikov AI.
Acta
Naturae
2010,
2:
36
1c Mikhailopulo IA.
Miroshnikov AI.
Mendeleev
Commun.
2011,
21:
57
2 Lewkowics ES.
Iribarren AM.
Curr. Org. Chem.
2006,
10:
1197
3a Ouwerkerk N.
van Boom JH.
Lugtenburg J.
Raap J.
Eur.
J. Org. Chem.
2000,
861
3b Ouwerkerk N.
Steenweg M.
De Ruijter M.
Brouwer J.
van Boom JH.
Lugtenburg J.
Raap J.
J. Org. Chem.
2002,
67:
1480
4a Ogawa J.
Saito K.
Sakai T.
Horinouchi N.
Kawano T.
Matsumoto S.
Sasaki M.
Mikami Y.
Shimizu S.
Biosci.,
Biotechnol., Biochem.
2003,
67:
933
4b Ishige T.
Honda K.
Shimizu S.
Curr.
Opin. Chem. Biol.
2005,
9:
174
5a Horinouchi N.
Ogawa J.
Kawano T.
Sakai T.
Saito K.
Matsumoto S.
Sasaki M.
Mikami Y.
Shimizu S.
Appl. Microbiol.
Biotechnol.
2006,
71:
615
5b Horinouchi N.
Ogawa J.
Kawano T.
Sakai T.
Saito K.
Matsumoto S.
Sasaki M.
Mikami Y.
Shimizu S.
Biosci.,
Biotechnol., Biochem.
2006,
70:
1371
5c Horinouchi N.
Ogawa J.
Kawano T.
Sakai T.
Saito K.
Matsumoto S.
Sasaki M.
Mikami Y.
Shimizu S.
Biotechnol.
Lett.
2006,
28:
877
5d Ogawa J.
New
Biotechnol.
2009,
26:
75
6 Taverna-Porro M.
Bouvier LA.
Pereira CA.
Montserrat JM.
Iribarren AM.
Tetrahedron Lett.
2008,
49:
2642
7a Komatsu H.
Awano H.
J. Org. Chem.
2002,
67:
5419
7b Komatsu H.
Ikeda I.
Nucleosides, Nucleotides Nucleic Acids
2003,
22:
1685
8 Komatsu H.
Araki T.
Tetrahedron Lett.
2003,
44:
2899
9a Komatsu H.
Awano H.
Ishibashi H.
Oikawa I.
Araki T.
Nucleic
Acids Symp. Ser.
2003,
3:
101
9b Komatsu H.
Araki T.
Nucleosides, Nucleotides Nucleic Acids
2005,
24:
1127
10a Yamada K.
Matsumoto N.
Hayakawa H.
Nucleic Acids Symp. Ser.
2004,
48:
45
10b Yamada K.
Matsumoto N.
Hayakawa H.
Nucleosides,
Nucleotides Nucleic Acids
2009,
28:
1117
11 de Lederkremer RM.
Nahmad VB.
Varela O.
J. Org. Chem.
1994,
59:
690
12 Euzen R.
Ferrieres V.
Plusquellec D.
J.
Org. Chem.
2005,
70:
847 ;
and references cited therein
13 Hanessian S.
Lou B.
Chem. Rev.
2000,
100:
4443
14a MacDonald DL.
J. Org. Chem.
1962,
27:
1107
14b MacDonald DL.
Carbohydr. Res.
1966,
3:
117
14c MacDonald DL.
Carbohydr. Res.
1968,
6:
376
14d Mendicino J.
Hanna R.
J. Biol. Chem.
1970,
245:
6113
14e Chittenden GJF.
Carbohydr. Res.
1972,
25:
35
15 Wright RS.
Khorana HG.
J. Am. Chem. Soc.
1958,
80:
1994 ; see also detailed discussion in this paper
16 Maryanoff BE.
Reitz AB.
Nortey SO.
Tetrahedron
1988,
44:
3093
17 Aspinall GO.
Cottrell IW.
Matheson NK.
Can. J. Biochem.
1972,
50:
574
18 Kobayashi M.
Tetrahedron
2002,
58:
9365
19 Hanessian S.
Lu P.-P.
Ishida H.
J.
Am. Chem. Soc.
1998,
120:
13296
20 Plesner PE.
Klenow H.
Methods Enzymol.
1957,
3:
181
21 Sokolov VM.
Rusavskaya TN.
Studentsov EP.
Zaharov VI.
Ivanov MA.
Sochilin EG.
Zh.
Obshch. Khim.
1981,
51:
946 ; Chem. Abstr . 1981 , 95 , 133270
22 Kam BL.
Oppenheimer NJ.
Carbohydr. Res.
1979,
69:
308
23 Bock K.
Pedersen C.
Carbohydr. Res.
1973,
29:
331
24 Kam BL.
Barascut J.-L.
Imbach J.-L.
Carbohydr.
Res.
1979,
69:
135
25 Lichtenthaler FW.
Breunig J.
Fischer W.
Tetrahedron Lett.
1971,
12:
2825
26 It is noteworthy that a mixture of
the 1 α and 1 β furanosides¹5 is
unstable at r.t. giving rise to the formation of two new fractions
that have been isolated by silica gel column chromatography. One
of them consists of two triacetates (¹ H, ¹³ C
NMR). Detailed NMR analysis (¹ H, ¹³ C
NMR; COSY, HMBC, TOCSY, and NOE) along with the ab initio geometry
optimization (HyperChem, 8.1; in vacuo, basis set; 6-31G*)
of the relevant structures led us to conclusion that the major constituent
is 2,3,5-tri-O -acetyl-α-d -arabino-furanose and the minor is 2,3,4-tri-O -acetyl-β-d -arabino-pyranose.
The formation of the former as a byproduct was previously mentioned²² in
the transformation of methyl 2,3,5-tri-O -acetyl-α-d -arabinofuranoside into 1,2,3,5-tetra-O -acetyl-α-d -arabinofuranose
through the intermediate ¹ H NMR) supposedly acyclic closely related
isomeric tetraacetates, the structures of which have not yet been
established.
27 Asseline U.
Hau J.-F.
Czernecki S.
Diguarher T.
Perlat M.-C.
Valery J.-M.
Thuong NT.
Nucleic
Acids Res.
1991,
19:
4067
28 Esipov RS.
Gurevich AI.
Chuvikovsky DV.
Chupova LA.
Muravyova TI.
Miroshnikov AI.
Protein
Expr. Purif.
2002,
24:
56
29 Averett DR.
Koszalka GW.
Fyfe JA.
Roberts GB.
Purifoy DJ.
Krenitsky TA.
Antimicrob.
Agents Chemother.
1991,
35:
851
30 Roivainen J.
Elizarova T.
Lapinjoki S.
Mikhailopulo IA.
Esipov RS.
Miroshnikov AI.
Nucleosides, Nucleotides
Nucleic Acids
2007,
26:
905
31 Tintagel Ltd, 2nd Floor, Eton Tower,
8 Hysan Avenue, Causeway Bay, Hong Kong; Tel.: +852(2910)7843;
Fax: +852(2910)7844; E-mail: kacin@netvigator.com.
32 Montgomery JA.
Hewson K.
J. Med. Chem.
1969,
12:
498
33 Mikhailopulo IA.
Kalinichenko E. N.
Zaitseva G.
V.
Akhrem AA.
Biol.
Mass. Spectrom.
1982,
9:
225
34 Chattopadhyaya J.
Reese C. B.
Synthesis
1978,
908
35 Schinazi RF.
Chen M. S.
Prusoff WH.
J.
Med. Chem.
1979,
22:
1273
