A. J. Walz, M. J. Miller / Tetrahedron Letters 48 (2007) 5103–5105
5105
In summary, synthetic methodology has been disclosed
that allows for the one-pot coupling of N1–Boc/N1–
OBn butyrate-derived b-lactams with an amine in the
presence of unprotected hydroxamic acids to form new
cobactin analogs. The incorporation of these com-
pounds into full mycobactin analogs and their biological
activity is under consideration.
a
b
N
HN
10a,b
N
BnO
6a Y = CH3 (
6b Y = CH3 (
O
O
Boc
O
6c,d
R
S
).
).
c
O
+
6c,d
N
N
N
H2N
OH
OH
H
O
O
4a
BocHN
3c,d
Acknowledgments
Scheme 2. Reagents and conditions: (a) SmI2, H2O, THF, 0 °C to rt,
3 h, (60–65%); (b) (BOC)2O, DMAP, THF, rt, 16 h, (80–89%); (c)
KCN, 18-crown-6 ether, CH3CN, rt, 24–48 h, (79–86%).
This research was supported by the NIH (AI054193).
M.J.M. gratefully acknowledges the kind hospitality of
the HKI and the University of Notre Dame for a sab-
batical opportunity.
the in situ generation of the hypervalent cyano-silicate
was accomplished with TMSCN and TBAF. Stirring
the reagents in the presence of the cyclic aminohydr-
oxamic acid and the b-lactams led to the efficient
formation of the desired cobactin analogs as single
diastereomers.
References and notes
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H2 and 10% Pd–C or Pearlman’s catalyst for this reduc-
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tion of the N1–OBn functionality was accomplished on
b-lactams 6a,b followed by Boc protection. Utilization
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reactions provided the desired amine terminated cobac-
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Direct cleavage of the N–O bond of substituted 1-(benz-
yloxy)-2-azetidinones cannot be easily accomplished
using hydrogenation or other more common N–O bond
reduction protocols. Titanium(III) chloride has been
used in a two step procedure developed earlier in our
group.19 Romo subsequently reported a samarium di-
iodide-mediated reduction of the N–O bond of a func-
tionalized 1-(benzyloxy)-2-azetidinone.13 The procedure
was adapted from the work of Keck and co-workers.20
Use of the samarium protocol allowed elaboration of
the 4-(methyl)-1-(benzyloxy)-2-azetidinones 6a,b to their
Boc-protected coupling precursors 6c,d as shown in
Scheme 2. SmI2 N–O bond reductions of these substrates
proceeded in 60–65% yield after chromatography. Boc
protection of the intermediate 4-(methyl)-1H-2-azetidi-
nones led to the desired products in acceptable yields.
With the necessary components in hand, coupling reac-
tions between the amino hydroxamic acid 4a and the b-
lactams 6c,d were successfully accomplished, as also
shown in Scheme 2, to give the desired separate diaste-
reomers of cobactin analogs 3c,d.
19. Mattingly, P. G.; Miller, M. J. J. Org. Chem. 1980, 45,
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20. Keck, G. E.; McHardy, S. F.; Wager, T. T. Tetrahedron
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