The Journal of Organic Chemistry
Article
(m, 4H), 4.27 (apparent q, J = 1.6 Hz, 1H), 4.65 (d, J = 3.6 Hz, 1H),
5.05 (d, J = 2.4 Hz, 1H), 5.79 (s, 1H), 5.97 (d, J = 3.6 Hz, 1H), 7.37
(m, 4H); 13C NMR (100 MHz, CDCl3) δ 26.0, 26.5, 41.8, 49.1 (δ, J =
4.6 Hz), 74.4 (d, J = 4.5 Hz), 75.8 (d, J = 4.6 Hz), 80.9 (d, J = 4.5 Hz),
83.5 (d, J = 12.1 Hz), 104.6, 112.7, 127.9, 128.7, 134.2 (d, J = 9.1),
134.6; 31P NMR (121.4 MHz, CDCl3) δ 5.2; HRMS (FAB-QMS)
[M + H]+ calcd for C18H24Cl3NO6P 486.0407, found 486.0379.
(5S,SP)-1,2-O-Isopropylidene-5-(4-chlorophenyl)-3,5-O-[N-bis(2-
chloroethyl)amino)phosphoryl]-α-D-xylofuranose (2b): white solid;
95 mg (39%); mp = 186−188 °C; [α]20D = +29.2 (c = 1 CHCl3); 1H
NMR (400 MHz, CDCl3) δ 1.31 (s, 3H), 1.42 (s, 3H), 3.42 (m, 4H),
3.62 (m, 4H), 4.51 (m, 1H), 4.85 (d, J = 3.6 Hz, 1H), 4.95 (dd, J =
17.4, 3.9 Hz, 1H), 5.41 (s, 1H), 6.18 (d, J = 3.6 Hz, 1H), 7.39 (m,
4H); 13C NMR (100 MHz, CDCl3) δ 26.2, 26.9, 41.7, 49.2 (d, J = 4.6
Hz), 76.9 (d, J = 6.8 Hz), 79.2 (d, J = 5.7 Hz), 83.0 (d, J = 6.8 Hz),
84.3, 105.6, 112.6, 128.3, 128.8, 134.3 (d, J = 8.0 Hz), 134.9; 31P NMR
(121.4 MHz, CDCl3) δ 1.97; HRMS (FAB-QMS) [M + H]+ calcd for
C18H24Cl3NO6P 486.0407, found 486.0379.
mixture prepared from livers of rats previously treated with
phenobarbital/β-naphthoflavone. The S9 mixture was prepared
according to Ames.7,17 We followed the OECD guideline (test no.
471) for testing of chemicals in bacterial reverse mutation tests.
Spontaneous reversion as well as positive control for mutagenicity was
included in each experiment. Cyclophosphamide was the positive
mutagenic control in the presence of the S9 mixture. A tested
compound was considered mutagenic when the number of induced
revertant colonies was increased by doubled in control plates, which is
consistent with a dose-dependent mutagenic effect.18 The data in
Table 1 showcase the revertant colonies
SD found in two inde-
pendent experiments (three replicated plates/experiment). Data from
spontaneous reversion of TA1535 strain as well as those from positive
control in the presence and absence of S9 mixture are included.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra; X-ray data for 2b and 4b (CIF). This
material is available free of charge via the Internet at http://
(5R,SP)-1,2-O-Isopropylidene-5-(4-chlorophenyl)-3,5-O-[N-bis(2-
chloroethyl)amino)phosphoryl]-α-D-xylofuranose (3b): yellow
1
syrup; 119.2 mg (49%); [α]20 = +20.5 (c = 1, CHCl3); H NMR
D
(400 MHz, CDCl3) δ 1.34 (s, 3H), 1.45 (s, 3H), 3.43 (m, 4H), 3.60
(m, 4H), 4.52 (td, J = 3.6, 1.6 Hz, 1H), 4.84 (d, J = 3.6 Hz, 1H), 4.89
(dd, J = 7.6, 3.6 HZ, 1H), 5.59 (dd, J = 6.4, 4.0 Hz, 1H), 6.18 (d, J =
3.6 Hz, 1H), 7.35 (m, 2H), 7.43 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 26.2, 26.8, 41.8, 49.5 (d, J = 4.6 Hz), 79.5 (d, J = 79.5 HZ),
79.6 (d, J = 8.0 Hz), 82.3 (d, J = 6.9 Hz), 84.4 (d, J = 6.8 Hz), 105.3,
112.7, 127.4, 129.3, 135.1, 135.2 (d, J = 6.8 Hz); 31P NMR (121.4
MHz, CDCl3) δ 3.77; HRMS (FAB-QMS) [M + H]+ calcd for
C18H24Cl3NO6P 486.0407, found 486.0377.
AUTHOR INFORMATION
Corresponding Authors
*Tel/Fax: +52 2222 2955500 ext 7391. E-mail: fernando.
*Tel/Fax: +52 2222 2955500 ext 7391. E-mail: leticia.
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(5R,RP)-1,2-O-Isopropylidene-5-(4-chlorophenyl)-3,5-O-[N-bis(2-
chloroethyl)amino)phosphoryl]-α-D-xylofuranose (4b): white solid;
102 mg (42%); mp = 152−153 °C; [α]20D = +7.0 (c = 1, CHCl3); 1H
NMR (400 MHz, CDCl3) δ 1.34 (s, 3H), 1.46 (s, 3H), 3.47 (m, 4H),
3.61 (m, 4H), 4.22 (m, 1H), 4.69 (d, J = 3.6 Hz, 1H), 4.92 (s, 1H),
5.74 (d, J = 16.8 Hz, 1H), 6.04 (d, J = 3.6 Hz, 1H), 7.40 (m, 2H), 7.59
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 26.0, 26.4, 41.9, 49.2 (d, J =
5.4 Hz), 76.5 (d, J = 5.7), 78.2 (d, J = 4.6 Hz), 81.4 (d, J = 6.9 Hz),
83.9 (d, J = 11.5 Hz), 104.3, 112.9, 127.7, 129.2, 134.9, 134.9 (d, J =
8.0 Hz), 134.9; 31P NMR (121.4 MHz, CDCl3) δ 0.17; HRMS (FAB-
QMS) [M + H]+ calcd for C18H24Cl3NO6P 486.0407, found 486.0385.
(5S,RP)-1,2-O-Isopropylidene-5-(4-methoxyphenyl)-3,5-O-[N-bis-
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from Consejo
Nacional de Ciencia y Tecnologia (CONACyT), project no.
151611. We also thank Sandra L. Hernandez Ojeda for
́
technical assistance.
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́
REFERENCES
(2-chloroethyl)amino)phosphoryl]-α-D-xylofuranose (1c): yellow
■
1
syrup; 118.1 mg (49%); [α]20 = −8.6 (c = 0.8, CHCl3); H NMR
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D
(400 MHz, CDCl3) δ 1.32 (s, 3H), 1.44 (s, 3H), 4.46 (m, 4H), 3.60
(m, 4H), 3.81 (s, 3H), 4.28 (apparent d, J = 1.2 Hz, 1H), 4.65 (d, J =
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(d, J = 9.0 Hz, 2H), 7.36 (d, J = 9.0 Hz, 2H); 13C NMR (75 MHz,
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(2-chloroethyl)amino)phosphoryl]-α-D-xylofuranose (4c): yellow
1
syrup; 77 mg (32%); H NMR (400 MHz, CDCl3) δ 1.34 (s, 3H),
̈
1.46 (s, 3H), 3.47 (m 4H), 3.60 (m, 4H), 3.82 (s, 3H), 4.25 (apparent
q, J = 1.6 Hz, 1H), 4.69 (d, J = 3.6 Hz, 1H), 4.99 (d, J = 1.6 Hz, 1H),
5.71 (d, J = 17.2 Hz, 1H), 6.03 (d, J = 3.6 Hz, 1H), 6.95 (d, J = 9.2 Hz,
2H), 7.55 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 26.0,
26.4, 41.9, 49.3 (d, J = 4.6 Hz), 55.3, 76.6, 78.3 (d, J = 5.7 Hz), 81.9 (d,
J = 6.8 Hz), 84.1 (d, J = 10.2 Hz), 104.2, 112.7, 114.3, 127.8, 128.4,
159.9; 31P NMR (121.4 MHz, CDCl3) δ −0.06; HRMS (FAB-QMS)
[M + H]+ calcd for C19H27Cl2NO7P 482.0902, found 482.0874.
Mutagenicity Test Conditions. All of the experiments were
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