156
M. Bosco et al. / Tetrahedron Letters 48 (2007) 153–157
iPrOH) followed by benzyloxycarbonylation of the result-
ing free amine (ZCl, CH2Cl2, Na2CO3, 2 h).
71.35, 71.24, 71.12, 66.27, 59.36, 55.27, 52.10 (d,
J = 6.4 Hz), 51.93 (d, J = 6.2 Hz), 51.13, 21.03 (d,
11. Initial experiments had shown that the benzyl groups
could not be removed at the end of the synthesis while
preserving the integrity of the prenyl chain.
12. In order to guarantee a better hydrolytic stability of the
final sugar phosphonates, experiments were run with (S)-
2,3-dihydrosolanesol, provided by Hoffmann–La Roche
(Basel), instead of commercial solanesol.
13. The use of 1 equiv each of DMAP and 2-(trimethylsi-
lyl)ethyl-para-nitrophenyl carbonate in dichloromethane
at room temperature has been recommended: Jewel, C. F.,
Jr.; Brinkmann, J.; Petter, R. C. Tetrahedron 1994, 50,
3849–3856, We used 2 equiv of these reagents in toluene at
50 °C.
J = 134.2 Hz).
HRMS
(electrospray)
calcd
for
C37H45NO7P (M+H+) 646.2934, found 646.2902. Com-
pound 16: 1H NMR (250 MHz, CDCl3, 300 K) d 5.09 (1H,
d, J = 4.2 Hz), 4.80 (1H, d, J = 3.8 Hz), 4.24 (1H, dd,
J = 5.3, 11.1 Hz), 4.04 (1H, dd, J = 7.1, 11.1 Hz), 3.75
(6H, d, J = 10.9 Hz), 3.65 (1H, ddd, J = 4.2, 9, 13.6 Hz),
3.29 (1H, ddd, J = 3.8, 5.3, 7.1 Hz), 2.13–1.82 (2H, m),
2.07 (3H, s), 2.04 (3H, s), 2.03 (3H, s). 31P NMR
(101.2 MHz, CDCl3, 300 K)
d
28.34. 13C NMR
(62.9 MHz, CDCl3, 300 K) d 170.78, 169.82, 169.66,
78.79, 77.89 (d, J = 13 Hz), 65.35, 61.78, 54.80 (d,
J = 6.4 Hz), 52.44 (d, J = 6.6 Hz), 25.34 (d, J = 142 Hz),
1
20.81, 20.80, 20.75. Compound 160: H NMR(250 MHz,
14. Selected analytical data: Compound 12 (anomeric mix-
ture): 1H NMR (250 MHz, CDCl3, 300 K) d 7.40–7.23
(15H, m), 4.99 (0.3H, d, J = 3.8 Hz), 4.71 (0.7H, d,
J = 2.3 Hz), 4.65–4.42 (6H, m), 4.38 (0.3H, dd, J = 1.9,
6 Hz), 4.38 (0.7H, q, J = 5.1 Hz), 4.1–3.96 (1.7H, m), 3.91
(0.7H, t, J = 2.3 Hz), 3.90 (0.3H, dd, J = 1.5, 3.8 Hz),
3.84–3.67 (3H, m), 3.80 (3H, s). Compound 13 (major
CD3OD, 300 K) d 5.33 (1H, d, J = 5.9 Hz), 5.02 (1H, s),
4.35 (1H, ddd, J = 3.2, 5.9, 11.3 Hz), 4.22–4.08 (4H, m),
3.74 (3H, d, J = 10.6 Hz), 3.70 (3H, d, J = 10.9 Hz), 4.13–
4.05 (1H, m), 3.05–2.71 (1H, m), 2.23–1.98 (1H, m), 2.13
(3H, s), 2.08 (3H, s), 2.05 (3H, s), 1.06–0.99 (92H, m), 0.01
(9H,s). 31P NMR (101.2 MHz, CDCl3, 300 K) d 28.34. 13
C
NMR (62.9 MHz, CDCl3, 300 K) d 170.73, 169.31, 169.12,
155.84, 74.92, 74.71, 64.42, 61.97, 52.55 (d, J = 6.3 Hz),
52.36 (d, J = 6.8 Hz), 23.90, 20.77, 17.72, ꢀ1.55. HRMS
(electrospray) calcd for C20H36NO11NaSiP (M+Na+)
548.1699, found 548.1693. Compound 20: 1H NMR
(400 MHz, CD3OD, 300 K) d 5.35 (1H, broad s), 5.10
(8H, t, J = 6.8 Hz), 5.04 (1H, s), 4.36 (2H, broad t,
J = 9 Hz), 4.25–4.17 (2H, m), 4.15 (1H, dd, J = 5,
10.8 Hz), 3.98 (1H, dd, J = 5, 9.2 Hz), 3.96–3.83 (2H,
m), 2.80–2.52 (1H, m), 2.28–1.88 (31H, m), 2.15 (3H, s),
2.07 (3H, s), 2.06 (3H, s), 1.74–1.52 (2H, m), 1.66 (3H, s),
1.59 (24H, s), 1.50–1.25 (2H, m), 1.22–1.13 (1H, m), 1.07
(2H, broad t, J = 9 Hz), 0.92 (3H, d, J = 6.4 Hz), 0.05
(9H, s). 31P NMR (161.9 MHz, CD3OD, 300 K) d 21.3.
13C NMR (100.69 MHz, CD3OD, 300 K) d 172.59, 171.38,
171.14, 135.82–135.75 (7C), 132.08, 126.07, 125.61–125.52
(7C), 77.18, 76.11, 65.23, 64.35, 63.33, 63.13, 58.80, 40.96–
40.86 (7C), 39.24, 38.51, 30.71, 27.88–27.62 (7C), 26.50,
25.96, 21.14, 20.78, 20.75, 20.08, 18.81, 17.84, 16.21 (7C),
ꢀ1.39 (3C). HRMS (electrospray) recorded on the deacet-
ylated POMe derivative obtained after NaOMe and
CH2N2 treatments, calcd for C58H102NO8PNaSi
(M+H+Na+) 1022.7010, found 1022.7092. Compound 8:
1H NMR (400 MHz, CD3OD, 300 K) d 5.10 (8H, t,
J = 6.8 Hz), 4.09 (2H, q, J = 7 Hz), 3.95–3.90 (2H, m),
3.88 (1H, broad s), 3.81 (1H, dd, J = 6.8, 11.6 Hz), 3.75–
3.68 (1H, m), 3.71 (1H, dd, J = 8, 11.6 Hz), 2.42–2.15 (2H,
m), 2.11–1.85 (30H, m), 1.81–1.14 (5H, m), 1.66 (3H, s),
1.59 (24H, s), 0.93 (3H, d, J = 6.5 Hz). 31P NMR
(161.9 MHz, CD3OD, 300 K) d 18.3. Compound 22
(mixture of anomers): 1H NMR (400 MHz, CDCl3,
1
isomer): H NMR (400 MHz, CDCl3, 300 K) d 7.32–7.24
(17H, m), 7.22 (2H, d, J = 8.4 Hz), 6.82 (2H, d,
J = 8.4 Hz), 4.72 (1H, ABq, J = 11.5 Hz), 4.65 (1H,
ABq, J = 11.3 Hz), 4.50 (1H, ABq, J = 11.5 Hz), 4.49
(1H, ABq, J = 11.3 Hz), 4.47 (1H, ABq, J = 12 Hz), 4.40
(1H, ABq, J = 12 Hz), 4.22 (1H, d, J = 6.6 Hz), 4.05 (1H,
dd, J = 6, 8 Hz), 3.89 (1H, d, J = 6.6 Hz), 3.76 (3H, s),
3.74 (1H, ABq, J = 12 Hz), 3.69 (3H, d, J = 10.8 Hz), 3.64
(3H, d, J = 10.8 Hz), 3.62 (1H, ABq, J = 12 Hz), 3.59 (1H,
dd, J = 6, 8.8 Hz), 3.52 (1H, dd, J = 8, 8.8 Hz), 3.47 (1H,
dd, J = 3.3, 9.2 Hz), 2.23 (1H, ddd, J = 3.3, 15.3, 21 Hz),
2.06 (1H, ddd, J = 9.2, 15.3, 17.1 Hz). 31P NMR
(161.9 MHz, CDCl3, 300 K)
d
30.5. 13C NMR
(100.69 MHz, CDCl3, 300 K) d 159.03, 138.52, 138.26,
137.91, 129.92 (2C), 128.44–127.44 (15C), 114.06 (2C),
78.80 (d, J = 3 Hz), 77.23, 75.48, 73.44, 73.12, 70.79,
66.62, 55.24, 52.42 (d, J = 6.9 Hz), 52.35 (d, J = 6.8 Hz),
50.61, 49.99, 25.35 (d, J = 135.9 Hz). Compound 14: 1H
NMR (400 MHz, CDCl3, 300 K) d 7.35–7.16 (17H, m),
6.82 (2H, d, J = 8.4 Hz), 4.53 (1H, ABq, J = 12 Hz), 4.48
(1H, ABq, J = 12 Hz), 4.46 (1H, ABq, J = 12 Hz), 4.42
(1H, ABq, J = 12 Hz), 4.37 (1H, ABq, J = 12 Hz), 4.25
(1H, ABq, J = 12 Hz), 3.98 (1H, d, J = 4.4 Hz), 3.90 (1H,
s), 3.88 (1H, ABq, J = 10.4 Hz), 3.79 (3H, s), 3.66 (6H, d,
J = 11.2), 3.64 (1H, ABq, J = 10.4 Hz), 3.40 (1H, ddd,
J = 3, 4.4, 11 Hz), 3.27 (1H, dd, J = 5.2, 12 Hz), 3.11–3.05
(2H, m), 2.41 (1H, ddd, J = 11, 15.6, 16 Hz), 1.96 (1H,
ddd, J = 3, 15.6,18.4 Hz). 31P NMR (161.9 MHz, CDCl3,
300 K) d 31.8. 13C NMR (100.69 MHz, CDCl3, 300 K) d
158.79, 138.52, 138.40, 138.18, 130.76, 130.45 (2C),
128.31–127.39 (15C), 113.60 (2C), 82.74 (d, J = 1.4 Hz),
82.21, 72.88, 71.97, 71.83, 70.73, 68.29, 61.28, 57.39, 55.22,
52.16 (d, J = 6.4 Hz), 52.10 (d, J = 6.6 Hz), 23.76 (d,
J = 136 Hz). HRMS (electrospray) calcd for C37H45NO7P
(M+H+) 646.2934, found 646.2902. Compound 15: 1H
NMR (400 MHz, CDCl3, 300 K) d 7.36–7.26 (17H, m),
6.83 (2H, d, J = 8.8 Hz), 4.55 (1H, ABq, J = 12.4 Hz),
4.48 (2H, s), 4.47 (1H, ABq, J = 12.4 Hz), 4.46 (2H, s),
4.13 (1H, s), 4.03 (1H, ABq, J = 14.2 Hz), 3.89 (1H, d,
J = 2.8 Hz), 3.80 (3H, s), 3.64 (1H, ABq, J = 14.2 Hz),
3.60 (1H, dd, J = 5.2, 9.6 Hz), 3.55–3.47 (2H, m), 3.53
(3H, d, J = 10.8 Hz), 3.51 (3H, d, J = 10.8 Hz), 3.16–3.12
(1H, m), 2.14 (1H, ddd, J = 3.6, 15.6, 18.8 Hz), 2.05 (1H,
td, J = 10, 15.6 Hz). 31P NMR (161.9 MHz, CDCl3,
300 K) d 32.0. 13C NMR (100.69 MHz, CDCl3, 300 K) d
158.60, 138.74, 138.37, 138.25, 131.01, 129.30 (2C),
128.29–127.39 (15C), 113.71 (2C), 86.52, 85.11, 73.21,
300 K)
d 5.17 (0.33H, d, J = 3.2 Hz), 5.14 (0.66H,
dd, J = 2.5, 3 Hz), 5.04 (0.66H, t, J = 2.5 Hz), 4.88
(0.33H, d, J = 2.8 Hz), 4.39 (0.66H, dq, J = 3, 7 Hz),
4.36–4.31 (0.33H, m), 4.27–4.16 (2H, m), 4.14–4.11
(0.66H, m), 4.08 (4H, quint, J = 6.8 Hz), 3.96–3.93
(0.33H, m), 2.30–2.20 (0.33H, m), 2.17 (1.32H, dd, J = 7,
18 Hz), 2.11–2.03 (9.33H, m), 1.28 (4H, t, J = 6.8 Hz),
1.27 (2H, t, J = 6.8 Hz). 31P NMR (161.9 MHz, CDCl3,
300 K) d 28.06 (0.33P), 27.31 (0.66P). Compound 9
(mixture of epimers): 1H NMR (400 MHz, CDCl3,
300 K) d 5.11 (8H, t, J = 6.3 Hz), 4.28 (0.33H, qd,
J = 3.3, 7 Hz), 4.11–4.01 (2.66H, m), 3.97–3.94 (1H, m),
3.91 (0.33H, d, J = 3.3 Hz), 3.88–3.82 (1.32H, m), 3.78–
3.73 (0.33H, m), 3.68 (1H, dd, J = 3.5, 12 Hz), 3.63 (1H,
dd, J = 7, 12 Hz), 2.22–1.95 (32H, m), 1.75–1.69 (1H, m),
1.67 (1H, s), 1.66–1.59 (1H, m), 1.60 (24H, s), 1.51–1.44
(1H, m), 1.43–1.32 (1H, m), 1.29–1.21 (1H, m), 0.93 (3H,