1925
Scheme 2.
In conclusion, we were able to synthesize 4-[(diethylphosphono)-20,20-difluoro-10-hydroxy-
ethyl]phenyl-alanine under a Fmoc protected form convenient for use in solid phase peptide synthesis.
Our next goal will be the preparation of stereochemically defined compounds and further incorporation
of these molecules into peptides of PTP autophosphorylation sites.
Acknowledgements
Financial support from la ‘Ligue contre le Cancer’, le ‘Conseil Regional d’Aquitaine’ and C.I.E.S.
(SC) is greatly acknowledged.
References
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12. Groves, M. R.; Yao, Z. J.; Roller, P. P.; Burke, T. R.; Barford, D. Biochemistry 1998, 37, 17 773–17 783.
13. Berkowitz, D. B.; Eggen, M. J.; Shen, Q.; Shoemaker, R. K. J. Org. Chem. 1996, 61, 4666–4675.
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15. Patwardhan, S. A.; Dev, S. Synthesis 1974, 348–349.
16. Burke, T. R.; Russ, P.; Lim, B. Synthesis 1991, 1019–1020.
17. Diethyldifluoromethylphosphonate was obtained by the modification of the reported method. Soborovskii, L. Z.; Baina F.
J. Gen. Chem. USSR 1959, 29, 1115–1117.
18. Satisfactory spectroscopic data (1H NMR 200.13 MHz, 13C NMR 50.32 MHz, IR and MS (FAB)) were obtained for
1
3
3
all compounds. Compound 4a, H NMR (CDCl3) 1.31 (m, 6H, JH–H=7.1 Hz, CH3CH2OP); 4.20 (m, 4H, JH–H=7.1 Hz,
3JH–P=7.3 Hz, 5JH–F=2.3 Hz, CH3CH2OP); 4.41 (d, 1H, 3JH–H=4.7 Hz, CHOH); 5.23 (dq, 1H, 3JH–H=4.7 Hz, 3JH–F=4.6 Hz,
3JH–P=20.7 Hz, CHOH); 7.65 (d, 2H, 3JH–H=8.2 Hz, CHar3,5); 7.88 (d, 2H, 3JH–H=8.2 Hz, CHar2,6); 10.0 (s, 1H, CHO); 13
C
NMR (CDCl3) 16.24 (d, 3JC–P=5.2 Hz, CH3CH2OP); 65.05, 65.25 (2d, 2JC–P=7.2 Hz, CH3CH2O); 72.8 (m (ddd), 2JC–P=14.5
Hz, JC–F=21.7, 26.2 Hz, CHOH); 110.5–125.3 (m (ddd), JC–P=206.3, JC–F=264.7, 273.1 Hz, CF2); 128.79 (s, Car3,5); 129.3
(s, Car2,6); 136.4 (s, C1ar); 141.5 (d, JCP=6.04 Hz, C4ar); 92.03 (s, CHO); IR (cm−1) 3304 (OH); 2994 (ar. C-H); 1695
(C_O); 1608 (ar. C–C); 1247 ((EtO)2P_O); 1208 (C–F); 1062 (P_O); MS (FAB) m/e 322.8 [M+1]+, 345.0 [M+23]+,
304.9 [M−18]+, 276.8 [M−45]+, exact: 322.2. Analysis calcd for C13H17F205P: C, 48.45; H, 5.32; found: C, 48.41; H,
5.52; mp 93–94°C from Et2O.
19. Compound 5 was synthesized in 97% yield by halide displacement from the ethyl bromoacetate and sodium azide in water
in the presence of tetrabutylammonium bromide as a phase-transfer catalyst.
20. Compound 9a: 1H NMR (MeOH-D4) 1.25 (m, 6H, 3JH–H=7.2 Hz, CH3CH2OP); 2.95 (m, 2H, 3JH–H=6 Hz, Hβ); 4.10 (m, 4H,
3
3
JH–H=7 Hz, 3JH–P=7.3 Hz, 5JH–F=2.2 Hz, CH3CH2OP,); 4.22 (t, 1H, 3JH–H=7 Hz, fluorenyl H9 ); 4.35 (dd, 1H, JH–H=7.10
0