8152
O. Monasson et al. / Tetrahedron Letters 48 (2007) 8149–8152
for performing the cyclisation in lactam ring were
HATU/HOBt in excess with diisopropylethylamine in
DMF. Indeed, these conditions allowed the obtention
of the expected diazepanone 15, although in a modest
30% yield. Obviously, further goal was to improve the
yield of the diazepanone formation and that was finely
done by inverting the order of the last steps of the syn-
thesis (Scheme 5). Thus, acidolysis of tert-butyl ester of
8 was first carried out by treatment with trifluoroacetic
acid in CH2Cl2 and concommitant lactonisation
occurred leading lactone 16 in 80% yield.
References and notes
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Then, reduction of the azido group of 16 by hydrogen-
olysis in the presence of ammonium formate and Pd/C
led to simultaneous isomerisation of the lactone into
the required lactam 15 in 84% yield. In an analogous
manner, the diastereoisomeric diazepanone 18 could
be obtained from the azido derivative 9 through the
intermediate lactone 17. The latter conditions involving
7. Isono, K.; Uramoto, M.; Kusakabe, H.; Kimura, K.;
Izaki, K.; Nelson, C. C.; McCloskey, J. A. J. Antibiot.
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a
lactonisation–lactamisation two-step sequence
8. For scaffolds with a seven-membered diazepane ring, see
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revealed much more powerful in terms of both yield
and purification as compared to the initial route.
In conclusion, we developed a straightforward route to
two enantiomerically pure polyfunctionalised diazepa-
none scaffolds from easily available L-serine deriva-
tive and azido epoxide resulting from L-ascorbic or
D-isoascorbic acid. The described synthesis relies on
three key reactions which are nucleophilic opening of
the epoxide by the secondary amine of the amino
acid followed by a two-step procedure involving a
lactonisation–lactamisation sequence and affording the
targeted diazepanone in 45% overall yield. The achieve-
ment of 1,4-diazepan-3-one synthesis in good yield and
displaying orthogonally protected highly differentiated
functions and various configurations is of general
interest in the scaffold field. It should now allow
the obtention of a library of liposidomycins analogs.
Current work is in progress towards this goal.
13. Le Merrer, Y.; Gravier-Pelletier, C.; Guerrouache, M.;
Depezay, J. C. Tetrahedron Lett. 1998, 39, 385–388.
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15. The duration of this reaction could be decreased to 2 min
by running it under microwave irradiation at 70 °C (CEM
DiscoverÒ). However, yield was not improved and part of
starting material was always recovered.
16. Dauber-Osguthorpe, P.; Roberts, V. A.; Osguthorpe, D.
J.; Wolff, J.; Genest, M.; Hagler, A. T. Proteins: Struct.
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Acknowledgements
We gratefully acknowledge the European Community
for the financial support of the Eur-INTAFAR inte-
grated project within the 6th PCRDT framework (Con-
tract No. LSHM-CT-2004-512138). We thank Dr O.
Andriuzzi for improving azido epoxide synthesis.