Prenyl Pyrophosphonates
J ournal of Medicinal Chemistry, 2004, Vol. 47, No. 18 4609
1.31 (t, J 13-12 7.1 Hz, 6H, H-13), 1.58 (s, 3H, H-11), 1.6 (s, 3H,
CH3), 1.65 (s, 3H, CH3), 1.66-1.88 (m, 2H, H-2), 1.9-2.12 (m,
4H, H-5 and H-6), 2.18-2.38 (m, 2H, H-1), 3.97-4.18 (q, 4H,
H-12), 5.06 (m, 1H, H-7), 5.1 (m, 1H, H-3); 31P NMR (CDCl3)
δ 33.2; 13C NMR (CDCl3) δ 16.22-16.38 (2C, C-13), 16.91-
18.08 (2C, C-10 and C-11), 21.39 (d, J 2-P 4.6 Hz, 1C, C-2), 26.08
(1C, C-9), 26.35 (d, J 1-P 138.8 Hz, 1C, C-1), 22.97 (1C, C-6),
39.97 (1C, C-5), 61.78-61.85 (2C, C-12), 123.41 (d, J 3-P 17.3
Hz, 1C, C-3), 123.82 (1C, C-7), 131.88 (1C, C-8), 136.76 (1C,
C-4); MS FAB+ (NOBA) m/z 289 (M + H)+. Anal. (C15H29O3P)
C, H.
C-3), 133.87 (1C, C-8), 136.8 (1C, C-4); MS FAB+ (GT) m/z 330
(M -2NH4 +5H)+, 313 (M -3NH4 +4H)+. Anal. (C11H31N3O6P2)
C, H, N.
Tr ia m m on iu m 4-m eth yl-4-p en ten ylp yr op h osp h on a te
(50): 52% yield; Rf ) 0.5, 27% aqueous ammonia/2-propanol,
4:6; 1H NMR (D2O) δ 1.52-1.71 (m, 4H, H-2 and H-3), 1.62 (s,
3H, H-6), 2.0 (m, 2H, H-1), 4.66 (s, 1H, H-5), 4.7 (s, 1H, H-5);
31P NMR (D2O) δ -7.0 (d, J â-R 25.1 Hz, P-â), 20.3 (d, P-R); 13
C
NMR (D2O) δ 21.2 (d, J 2-P 4.0 Hz, 1C, C-2), 21.86 (1C, C6),
27.67 (d, J 1-P 136.7 Hz, 1C, C-1), 38.65 (d, J 3-P 18.4 Hz, 1C,
C-3), 110.03 (1C, C-5), 147.92 (1C, C-4); MS FAB+ (GT) m/z
262 (M - 2NH4 + 3H)+, 245 (M - 3NH4 + 4H)+. Anal.
(C6H23N3O6P2) C, H, N.
Dieth yl (4-m eth yl-4-p en ten yl)p h osp h on a te (44): 64%
yield; Rf ) 0.35, ethyl acetate; 1H NMR (CDCl3) δ 1.31 (t, J 8-7
3.5 Hz, 6H, H-8), 1.72 (s, 3H, H-6), 1.6-1.82 (m, 4H, H-2 and
H-3), 2.1 (m, 2H, H-1), 4.0-4.20 (q, 4H, H-7), 4.7 (s, 1H, H-5),
4.76 (s, 1H, H-5); 31P NMR (CDCl3) δ 33.7; 13C NMR (CDCl3)
δ 16.63-16.72 (2C, C-8), 21.64 (d, J 2-P 4.4 Hz, 1C, C-2), 21.98
(1C, C-6), 27.41 (d, J 1-P 131.7 Hz, 1C, C-1), 34.78 (d, J 3-P 16.5
Hz, 1C, C-3), 61.82-61.93 (2C, C-7), 110.78 (1C, C-5), 148.13
(1C, C-4); MS FAB+ (NOBA) m/z 221 (M + H)+. Anal.
(C10H21O3P) C, H.
Tetr a a m m on iu m 4-m eth ylp en t-3-en yltr ip h osp h on a te
(51): 15% yield; Rf ) 0.21, SiO2, 27% aqueous ammonia)/2-
1
propanol, 4:6; H NMR (D2O) δ 1.54 (s, 3H, H-5), 1.56-1.62
(m, 2H, H-2), 1.58 (s, 3H, H-6), 2.10-2.28 (m, 2H, H-1), 5.15
(m, 1H, H-3); 31P NMR (D2O) δ -21.1 (dd, J â-R 24.0 Hz and
J
â-γ 19.6 Hz, P-â), -5.7 (d, P-γ), 21.9 (d, P-R); 13C NMR (D2O)
δ 17.20 (1C, C-5), 22.12 (d, J 2-P 4.0 Hz, 1C, C-2), 24.10 (1C,
C-6), 28.79 (d, J 1-P 135.7 Hz, 1C, C-1), 124.96 (d, J 3-P 18.9
Hz, 1C, C-3), 133.96 (1C, C-4); MS FAB+ (GT) m/z 325 (M -
4NH4 + 5H)+.
P h osp h on ic a cid s w er e obta in ed a ccor d in g to th e
sa m e p r oced u r e u sed for com p ou n d s 14-18. 4-Meth yl-
3-p en ten ylp h osp h on ic a cid (45): 69% yield; Rf ) 0.29, 27%
aqueous ammonia/2-propanol, 4:6; 1H NMR (CDCl3) δ 1.61 (s,
3H, H-5), 1.65-1.88 (m, 2H, H-2), 1.68 (s, 3H, H-6), 2.15-2.32
(m, 2H, H-1), 5.04-5.2 (m, 1H, H-3), 8.0 (s, 2H, POH); 31P NMR
(CDCl3) δ 34.5; 13C NMR (CDCl3) δ 18.05 (1C, C-5), 21.81 (d,
J 2-P 4.1 Hz, 1C, C-2), 24.76 (1C, C-6), 26.87 (d, J 1-P 142.3 Hz,
1C, C-1), 122.51 (d, J 3-P 19.5 Hz, 1C, C-3), 133.75 (1C, C-4);
MS FAB+ (NOBA) m/z 165 (M + H)+, 187 (M + Na)+.
(E)-4,8-Dim eth yl-3,7-n on a d ien ylp h osp h on ic a cid (46):
98% yield; Rf ) 0.4, 27% aqueous ammonia/2-propanol, 4:6;
1H NMR (CDCl3) δ 1.55-1.88 (m, 2H, H-2), 1.62 (s, 6H, 2CH3),
1.7 (s, 3H, CH3), 1.9-2.1 (m, 4H, H-5 and H-6), 2.17-2.41 (m,
2H, H-1), 5.0-5.22 (m, 2H, H-3 and H-7), 9.45 (s, 2H, POH);
31P NMR (CDCl3) δ 36.8; 13C NMR (CDCl3) δ 15.68-18.1 (2C,
C-10 and C-11), 21.25 (d, J 2-P 4.5 Hz, 1C, C-2), 26.10 (1C, C-9),
26.6 (d, J 1-P 142.9 Hz, 1C, C-1), 26.84 (1C, C-6), 39.99 (1C,
C-5), 123.33 (d, J 3-P 18.6 Hz, 1C, C-3), 124.58 (1C, C-7), 131.87
(1C, C-8), 136.8 (1C, C-4); MS FAB+ (NOBA) m/z 233 (M +
H)+, 255 (M + Na)+.
4-Meth yl-4-p en ten ylp h osp h on ic a cid (47): 76% yield; Rf
) 0.4, 27% aqueous ammonia/2-propanol, 4:6; 1H NMR (CDCl3)
δ 1.73 (s, 3H, H-6), 1.6-1.85 (m, 4H, H-2 and H-3), 2.11 (m,
2H, H-1), 4.71 (s, 1H, H-5), 4.77 (s, 1H, H-5), 8.39 (s, 2H, POH);
31P NMR (CDCl3) δ 37.7; 13C NMR (CDCl3) δ 21.51 (d, J 2-P 4.2
Hz, 1C, C-2), 21.73 (1C, C-6), 27.77 (d, J 1-P 133.2 Hz, 1C, C-1),
38.61 (d, J 3-P 17.5 Hz, 1C, C-3), 110.13 (1C, C-5), 147.63 (1C,
C-4); MS FAB+ (NOBA) m/z 165 (M + H)+, 187 (M + Na)+.
P yr op h osp h on a tes w er e obta in ed a ccor d in g to th e
sa m e p r oced u r e u sed for com p ou n d s 24-28. Tr ia m m o-
n iu m 4-m eth yl-3-p en ten ylp yr op h osp h on a te (48): 50%
yield; Rf ) 0.35, 27% aqueous ammonia/2-propanol, 4:6; 1H
NMR (D2O) δ 1.52 (s, 3H, H-5), 1.55-1.6 (m, 2H, H-2), 1.57
(s, 3H, H-6), 2.0-2.22 (m, 2H, H-1), 5.14 (m, 1H, H-3); 31P NMR
(D2O) δ -7.0 (d, J â-R 25.2 Hz, P-â), 19.5 (d, P-R); 13C NMR
(D2O) δ 17.24 (1C, C-5), 21.93 (d, J 2-P 3.9 Hz, 1C, C-2), 24.02
(1C, C-6), 28.29 (d, J 1-P 135.1 Hz, 1C, C-1), 124.87 (d, J 3-P
18.8 Hz, 1C, C-3), 133.82 (d, J 4-P 1.5 Hz, 1C, C-4); MS FAB+
(GT) m/z 279 (M - NH4 + 2H)+, 262 (M - 2NH4 + 3H)+, 245
(M - 3NH4 + 4H)+. Anal. (C6H23N3O6P2) C, H, N.
Tet r a a m m on iu m (E)-4,8-d im et h yln on a -3,7-d ien ylt r i-
p h osp h on a te (52): 9.61% yield; Rf ) 0.29, SiO2, 27% aqueous
ammonia)/2-propanol, 4:6; 1H NMR (D2O) δ 1.45 (s, 3H, CH3),
1.48 (s, 3H, CH3), 1.52 (s, 3H, CH3), 1.54-1.69 (m, 2H, H-2),
1.77-1.99 (m, 4H, H-5 and H-6), 2.0-2.19 (m, 2H, H-1), 5.03
(m, 1H, H-7), 5.12 (s, 1H, H-3); 31P NMR (D2O) δ -20.7 (dd,
J
â-R 23.9 Hz and J â-γ 20.6 Hz, P-â), -5.4 (d, P-γ), 21.4 (d, P-R);
13C NMR (D2O) δ 15.51 (1C, C-10), 17.27 (1C, C-11), 21.78 (d,
J 2-P 3.8 Hz, 1C, C-2), 25.13 (1C, C-9), 26.10 (1C, C-6), 28.37
(d, J 1-P 135.2 Hz, 1C, C-1), 39.09 (1C, C-5), 124.68 (d, J 3-P
15.5 Hz, 1C, C-3), 124.73 (1C, C-7), 133.82 (1C, C-8), 137.06
(1C, C-4); MS FAB+ (GT) m/z 393 (M - 4NH4 + 5H)+.
Tetr a a m m on iu m 4-m eth ylp en t-4-en yltr ip h osp h on a te
(53): 14% yield; Rf ) 0.26, SiO2, 27% aqueous ammonia)/2-
propanol, 4:6; 1H NMR (D2O) δ 1.48-1.52 (m, 4H, H-2 and
H-3), 1.58 (s, 3H, H-6), 1.98 (m, 2H, H-1), 4.62 (s, 1H, H-5),
4.7 (s, 1H, H-5); 31P NMR (D2O) δ -21.0 (dd, J â-R 24.4 Hz and
J
â-γ 20.3 Hz, P-â), -5.9 (d, P-γ), 22.1 (d, P-R); 13C NMR (D2O)
δ 21.08 (d, J 2-P 4.3 Hz, 1C, C-2), 21.83 (1C, C-6), 27.64 (d, J 1-P
137.1 Hz, 1C, C-1), 38.45 (d, J 3-P 18.3 Hz, 1C, C-3), 110.16
(1C, C-5), 147.59 (1C, C-4); MS FAB+ (GT) m/z 325 (M - 4NH4
+ 5H)+.
Tr ia m m on iu m r,γ-(4-m eth ylp en t-3-en yl)tr ip h osp h o-
n a te (54): 4% yield; Rf ) 0.7 SiO2, 27% aqueous ammonia)/
2-propanol, 4:6; 1H NMR (D2O) δ 1.47 (s, 6H, H-6), 1.53 (s,
6H, H-5), 1.54-1.68 (m, 4H, H-2), 1.95-2.2 (m, 4H, H-1), 5.08
(m, 2H, H-3); 31P NMR (D2O) δ -21.88 (t, J â-R ) J â-γ 25.5 Hz,
P-â), 20.91 (d, 2P, P-R and P-γ); 13C NMR (D2O) δ 17.24 (2C,
C-5), 21.98 (d, J 2-P 4.0 Hz, 2C, C-2), 25.11 (2C, C-6), 28.1 (d,
J 1-P 131.1 Hz, 2C, C-1), 124.72 (d, J 3-P 21.2 Hz, 2C, C-3), 133.9
(d, J 4-P 1.2 Hz, 2C, C-4); MS FAB+ (GT) m/z 391 (M - 3NH4
+ 4H)+.
Tr ia m m on iu m r,γ-[(E)-4,8-d im et h yln on a -3,7-d ien yl]-
tr ip h osp h on a te (55): 5% yield; Rf ) 0.75, SiO2, 27% aqueous
ammonia)/2-propanol, 4:6; 1H NMR (D2O) δ 1.46 (s, 6H, H-11),
1.53 (s, 12H, H-9 and H-10), 1.69-2.0 (m, 8H, H-5 and H-6),
2.08-2.12 (m, 4H, H-1), 4.95-5.05 (m, 2H, H-7), 5.06-5.17
(m, 2H, H-3); 31P NMR (D2O) δ -22.2 (t, J â-R ) J â-γ 25.6 Hz,
1P, P-â), 20.7 (d, 2P, P-R and P-γ); 13C NMR (D2O) δ 15.53
(2C, C-10), 17.32 (2C, C-11), 21.85 (d, J 2-P 3.8 Hz, 2C, C-2),
25.27 (2C, C-9), 26.18 (1C, C-6), 29.02 (d, J 1-P 134.9 Hz, 2C,
C-1), 40.18 (2C, C-5), 124.80 (d, J 3-P 15.7 Hz, 2C, C-3), 124.81
(2C, C-7), 133.89 (2C, C-8), 137.10 (2C, C-4); MS FAB+ (GT)
m/z 527 (M - 3NH4 + 4H)+.
(E)-Tr ia m m on iu m 4,8-d im eth yl-3,7-n on a d ien ylp yr o-
p h osp h on a te (49): 46% yield; Rf ) 0.47, 27% aqueous
ammonia/2-propanol, 4:6; 1H NMR (D2O) δ 1.42 (s, 3H, H-11),
1.46 (s, 3H, CH3), 1.49 (s, 3H, CH3), 1.5-1.65 (m, 2H, H-2),
1.73-1.95 (m, 4H, H-5 and H-6), 1.95-2.15 (m, 2H, H-1), 4.99
(m, 1H, H-7), 5.09 (m, 1H, H-3); 31P NMR (D2O) δ -6.4 (d,
J â-R 25.1 Hz, P-â), 19.3 (d, P-R); 13C NMR (D2O) δ 15.56 (1C,
C-10), 17.3 (1C, C-11), 21.99 (d, J 2-P 4.4 Hz, 1C, C-2), 25.18
(1C, C-9), 26.15 (1C, C-6), 28.39 (d, J 1-P 134.4 Hz, 1C, C-1),
39.15 (1C, C-5), 124.74 (1C, C-7), 125.08 (d, J 3-P 18.8 Hz, 1C,
Tr ia m m on iu m r,γ-(4-m eth ylp en t-4-en yl)tr ip h osp h o-
n a te (56): 12.5% yield; Rf ) 0.66, SiO2, 27% aqueous am-
monia)/2-propanol, 4:6; 1H NMR (D2O) δ 1.5-1.71 (m, 8H, H-2
and H-3), 1.62 (s, 6H, H-6), 2.01 (m, 4H, H-1), 4.67 (s, 2H, H-5),
4.70 (s, 2H, H-5); 31P NMR (D2O) δ -22.1 (t, J â-R ) J â-γ 25.6
Hz, 1P, P-â), 21.7 (d, 2P, P-R and P-γ); 13C NMR (D2O) δ 21.14
(d, J 2-P 4.1 Hz, 2C, C-2), 21.85 (2C, C-6), 27.75 (d, J 1-P 137.4