O. Monasson et al. / Tetrahedron: Asymmetry 20 (2009) 2320–2330
2329
4.31. (2R,3S)-3-Azido-4-tert-butyldiphenylsilyloxy-1,2-epoxy-
as a white foam; [a]
D = +24 (c 1.0, CH2Cl2); 1H NMR d 7.69–7.26
butane 38
(m, 15H, Har.), 6.1 (d, 1H, JH1–H7 = 5 Hz, H1), 4.56 (s, 2H, CH2Ph),
4.01 (m, 1H, H7), 3.92 (dd, 1H, JCH2bOSi–H7 = 3.5 Hz, JCH2Osi = 10.8 Hz,
CH2bOSi), 3.80 (m, 3H, JCH2OBn–H3 = 3.7 Hz, CH2OBn, H6), 3.78 (dd,
1H, JCH2aOSi–H7 = 3.5 Hz, JCH2OSi = 10.8 Hz, CH2aOSi), 3.38 (t, 1H,
JH3–CH2OBn = 3.7 Hz, H3), 3.15 (dd, 1H, JH5a–H5b = 15 Hz, JH5a–H6
= 3 Hz, H5a), 2.80 (dd, 1H, JH5a–H5b = 15 Hz, JH5b–H6 = 1.5 Hz, H5b),
2.48 (s, 3H, NMe), 1.11 (s, 9H, tBu); 13C NMR d 174.1 (C2); 137.7,
135.3, 132.6, 129.7, 128.2, 127.7, 127.4, 127.3 (Car.) 73.2 (CH2Ph),
72.0 (C3), 68.4 (C6), 67.8 (CH2OSi), 63.6 (CH2OBn), 58.1 (C5), 55.1
(C7), 44.8 (NMe), 19.0, 26.7 (tBu); HRMS calcd for (M+H)+
533.2836; found 533.2829.
From diol 37 (6 g, 16 mmol) and according to the general proce-
dure described above for epoxide 11 preparation, 5 g (88%) of the
epoxide 38 were obtained as a colourless oil, after flash chromato-
graphic purification (cyclohexane/EtOAc, 97:3, Rf 0.3); [
a
]
D = ꢁ24
(c 1.0, CH2Cl2); 1H NMR d 7.75–7.32 (2 m, 10H, Har.), 3.84–3.76
(m, 2H, H4), 3.25 (ddd, 1H, JH3–H4a = JH3–H4b = JH3–H2 ꢂ 5.9 Hz, H3),
3.04 (ddd, 1H, JH2–H3 = 5.9 Hz, JH2–H1a = 4.4 Hz, JH2–H1b = 2.5 Hz,
H2), 2.76 (dd, 1H, JH1a–H2 = 4.4 Hz, JH1a–H1b = 4.6 Hz, H1a), 2.64 (dd,
1H, JH1b–H2 = 2.5 Hz, JH1b–H1a = 4.6 Hz, H1b), 1.06 (s, 9H, tBu); 13C
NMR d 135.5, 132.7, 129.9, 127.8 (Car.), 64.4 (C3), 64.2 (C4), 51.7
(C2), 44.5 (C1), 26.7, 19.1 (tBu); HRMS calcd for (M+NH4)+
385.2060; found 385.2058. Anal. Calcd for C20H25N3O2Si: C,
65.36; H, 6.86; N, 11.43. Found: C, 65.50; H, 7.01; N, 11.54.
Acknowledgements
We gratefully acknowledge the European Community for the
financial support of the Eur-INTAFAR integrated project within
the 6th PCRDT framework (Contract No. LSHM-CT-2004-512138)
and for a doctoral grant to O.M. J.M. thanks la Ville de Paris for a
post-doctoral grant. We thank Geneviève Arnaud-Vincent (Centre
Technique de Langues, Université Paris Descartes) for her critical
reading of this manuscript.
4.32. tert-Butyl N-[(2R,3R)-3-azido-4-tert-butyldiphenylsilyl-
oxy-2-hydroxybutyl]-N0-methyl-O-benzyl-
L-serine 39
From the azido-epoxide 38 (2.4 g, 6.6 mmol) and tert-butyl O-
benzyl-N-methyl- -serine ester 22 (2.2 g, 8.6 mmol), the general
conditions described above for the epoxide opening and for com-
pounds 21 and 23 preparation, followed by flash chromatography
(cyclohexane/EtOAc, 4:1, Rf 0.5) afforded 2.7 g (65%) of the tertiary
L
References
amine 39 as an oil; [
a
]
D = ꢁ10 (c 1.0, CH2Cl2); 1H NMR d 7.70–7.28
1. For example, see: (a) Walsh, C.; Wright, G. Chem. Rev. 2005, 105, 391. and all
references of this volume dedicated to antibiotic resistance; (b) Talbot, G. H.;
Bradley, J.; Edwards, J., Jr.; Gilbert, D.; Scheld, M.; Bartlett, J. G. Clin. Infect. Dis.
2006, 42, 657–668.
2. van Heijenoort, J. Nat. Prod. Rep. 2001, 8, 503–519.
3. Bouhss, A.; Mengin-Lecreulx, D.; Le Beller, D.; van Heijenoort, J. Mol. Microbiol.
1999, 34, 576–585.
4. Boyle, D. S.; Donachie, W. D. J. Bacteriol. 1998, 180, 6429–6432.
5. (a) van Heijenoort J. Nat. Prod. Rep. 2001, 8, 503–519; (b) Bouhss, A.; Trunkfield,
A. E.; Bugg, T. D. H.; Mengin-Lecreulx, D. FEMS Microbiol. Rev. 2008, 32, 208–
233.
6. Bouhss, A.; Crouvoisier, M.; Blanot, D.; Mengin-Lecreulx, D. J. Biol. Chem. 2004,
279, 29974–29980.
(m, 15H, Har.), 4.53, 4.48 (AB, 2H, JAB = 12 Hz, CH2Ph), 3.96 (dd, 1H,
J4a–4b = 10.7 Hz, JH4a–H3 = 7.4 Hz, H4a), 3.86 (dd, 1H, JH4a–H4b
= 10.7 Hz, JH4b–H3 = 4.4 Hz, H4b), 3.75 (m, 1H, H2), 3.72 (dd, 1H,
0
0
0
0
0
0
0
JH3 a–H3 b = 10 Hz, JH3 b–H2 = 5.7 Hz, H3 b), 3.60 (dd, 1H, JH3 a–H3 b
0
0
0
0
0
= 10 Hz, JH3 a–H2 = 7 Hz, H3 a), 3.45 (dd, 1H, JH2 –H3 a = 7 Hz,
0
0
0
JH2 –H3 b = 5.7 Hz, H2 ), 3.35 (m, 1H, H3), 2.74–2.71 (m, 2H, H1),
2.34 (s, 3H, NMe), 1.40, 1.07 (2s, 18H, tBu); 13C NMR d 170.3
0
(C1 ), 137.9, 136.7, 136.2, 135.0, 132.9, 130.5, 129.2, 128.5, 127.7,
0
0
127.2 (Car.), 81.6 (OtBu), 73.3 (CH2Ph), 68.3 (C3 ), 67.6 (C2 , C2),
65.1 (C3, C4), 58.4 (C1), 38.0 (NCH3), 28.3, 26.9, 19.1 (tBu).
7. Known inhibitors of MraY, see for example: (a) Takatsuki, A.; Arima, K.;
Tamura, G. J. Antibiot. 1971, 24, 215–223; (b) Isono, K.; Uramoto, M.; Kusakabe,
H.; Kimura, K.; Izaki, K.; Nelson, C. C.; McCloskey, J. A. J. Antibiot. 1985, 38,
1617–1621; (c) Inukai, M.; Isono, F.; Takahashi, S.; Enokita, R.; Sakaida, Y.;
Haneishi, T. J. Antibiot. 1989, 42, 662–666; (d) Takeuchi, T.; Igarashi, M.;
Naganawa, H.; Hamada, M. PCT Int. Appl. 2001, 73, WO 2001012643.; (e)
Igarashi, M.; Nakagawa, N.; Doi, N.; Hattori, S.; Naganawa, H.; Hamada, M. J.
Antibiot. 2003, 56, 580–583; (f) Dini, C. Curr. Top. Med. Chem. 2005, 5, 1221–
1236. and references cited therein.
8. (a) Gravier-Pelletier, C.; Charvet, I.; Le Merrer, Y.; Depezay, J.-C. J. Carbohydr.
Res. 1997, 16, 129–141; (b) Le Merrer, Y.; Gravier-Pelletier, C.; Guerrouache, M.;
Depezay, J.-C. Tetrahedron Lett. 1998, 39, 385–388; (c) Gravier-Pelletier, C.;
Milla, M.; Le Merrer, Y.; Depezay, J.-C. Eur. J. Org. Chem. 2001, 3089–3096; (d)
Gravier-Pelletier, C.; Ginisty, M.; Le Merrer, Y. Tetrahedron: Asymmetry 2004, 15,
189–193; (e) Ginisty, M.; Gravier-Pelletier, C.; Le Merrer, Y. Tetrahedron:
Asymmetry 2006, 17, 142–150; (f) Monasson, O.; Ginisty, M.; Bertho, G.;
Gravier-Pelletier, C.; Le Merrer, Y. Tetrahedron Lett. 2007, 48, 8149–8152; (g)
Clouet, A.; Gravier-Pelletier, C.; Al-Dabbagh, B.; Bouhss, A.; Le Merrer, Y.
Tetrahedron: Asymmetry 2008, 19, 397–400.
9. For recent and selected synthetic approaches towards MraY inhibitors: (a)
Knapp, S.; Moriello, G. J.; Doss, G. A. Org. Lett. 2002, 4, 603–606; (b) Dini, C.;
Didier-Laurent, S.; Drochon, N.; Feteanu, S.; Guillot, J. C.; Monti, F.; Uridat, E.;
Zhang, J.; Aszodi, J. Bioorg. Med. Chem. Lett. 2002, 12, 1209–1213; (c) Lin, Y. I.; Li,
Z.; Francisco, G. D.; McDonald, L. A.; Davis, R. A.; Singh, G.; Yang, Y.; Mansour, T.
S. Bioorg. Med. Chem. Lett. 2002, 12, 2341–2344; (d) Howard, N. I.; Bugg, T. D. H.
Bioorg. Med. Chem. 2003, 11, 3083–3099; (e) Boojamra, C. G.; Lemoine, R. C.;
Blais, J.; Vernier, N. G.; Stein, K. A.; Magon, A.; Chamberland, S.; Hecker, S. J.;
Lee, V. J. Bioorg. Med. Chem. Lett. 2003, 13, 3305–3309; (f) Yamashita, A.;
Norton, E.; Petersen, P.; Rasmunssen, B. A.; Singh, G.; Yang, Y.; Mansour, T.;
Tarek, S.; Ho, D. M. Bioorg. Med. Chem. Lett. 2003, 13, 3345–3350; (g) Sarabia, F.;
Martin-Ortiz, L.; Lopez-Herrera, F. J. Org. Lett. 2003, 5, 3927–3930; (h) Ichikawa,
S.; Matsuda, A. Nucleosides, Nucleotides, Nucleic Acids 2005, 24, 319–329; (i)
Hirano, S.; Ichikawa, S.; Matsuda, A. Angew. Chem., Int. Ed. 2005, 44, 1854–1856;
(j) Sarabia, F.; Martin-Ortiz, L. Tetrahedron 2005, 61, 11850–11865; (k)
Bourdreux, Y.; Drouillat, B.; Greck, C. Lett. Org. Chem. 2006, 3, 368–370; (l)
Hirano, S.; Ichikawa, S.; Matsuda, a. J. Org. Chem. 2007, 72, 9936–9946; (m)
Kurosu, M.; Mahapatra, S.; Narayanasamy, P.; Crick, D. C. Tetrahedron Lett.
2007, 48, 799–803; (n) Drouillat, B.; Bourdreux, Y.; Perdon, D.; Greck, C.
Tetrahedron: Asymmetry 2007, 18, 1955–1963; (o) Hirano, S.; Ichikawa, S.;
Matsuda, A. Tetrahedron 2007, 63, 2798–2804; (p) Xu, X. H.; Trunkfield, A. E.;
4.33. (10R,3S,6R)-6-[(10-Azido-20-tert-butyldiphenylsilyloxy)-
ethyl]-3-benzyloxymethyl-4-methyl-morpholin-2-one 40
From the tert-butyl ester 39 (2.4 g, 3.8 mmol) and according to
the general procedure described above for the morpholinones 29
and 30 preparation, the morpholinone 40 was obtained and was
used without further purification in the next reaction. A sample
was purified by flash chromatography (cyclohexane/EtOAc, 4:1,
Rf 0.25); [
a
]
D = ꢁ29 (c 1.0, CH2Cl2); 1H NMR d 7.66–7.25 (m, 15H,
Har.), 4,61 (m, 1H, H6), 4.50, 4.44 (AB, 2H, JAB = 12 Hz, CH2Ph),
3.89, 3.76 (ABX, 2H, JAB = 10.8 Hz, JAX = 3.4 Hz, JBX = 5.4 Hz, H2 ),
3.86–3.80 (m, 3H, H1 , CH2OBn), 3.24 (t, 1H, JH3–CH2OBn = 2.6 Hz,
H3), 2.98 (dd, 1H, JH5a–H5b = 13.2 Hz, JH5a–H6 = 5,7 Hz, H5a), 2.65
(dd, 1H, JH5a–H5b = 13.2 Hz, JH5b–H6 = 3.6 Hz, H5b), 2.26 (s, 3H,
NMe), 1.04 (s, 9H, tBu); 13C NMR d 163.0 (C2), 136.2, 135.6,
132.6, 132.2, 130.3, 128.7, 128.4, 128.1 (Car.), 74.3 (CH2Ph), 73.5
(C6), 66.9 (C2 ), 62.4 (CH2OBn), 62.2 (C3), 61.2 (C1 ), 50.3 (C5), 40.3
(NCH3), 26.7, 19.1 (tBu).
0
0
0
0
4.34. (3S,6R,7R)-3-Benzyloxymethyl-7-tert-
butyldiphenylsilyloxymethyl-6-hydroxy-4-N-methyl-1,4-
diazepan-2-one 41
From morpholin-2-one 40 (3.79 mmol) the general procedure
described above for the diazepanone 16 and 28 preparation
according to the lactonisation–lactamisation sequence was carried
out except that the mixture was stirred for 60 h at 20 °C instead of
5 h. This was followed by flash chromatography (EtOAc/Et3N,
100:3‰, Rf 0.3) and afforded 1.69 g of the diazepanone 41 (84%)