G. Shen et al. / Bioorg. Med. Chem. Lett. 14 (2004) 5903–5906
5905
etherate.49 When initial conditionswere surveyed with 6
and 7, we observed that both the 4- and 7-phenolic moi-
eties were noviosylated in low to moderate yields. Fur-
ther experimentation proved that in the presence of
excess coumarin, the amount of dinoviosylated product
was drastically reduced and the desired 7-noviose prod-
uct, 8, wasprovided in good yield. The diaza-bridge con-
necting the phenyl and coumarin ringsesrved asa
masked amine, which could be cleaved under reducing
conditionsto provide the 3-amino coumarin 9. However,
9 turned out to be unstable under a variety of conditions,
including chromatography.
7. Laurin, P.; Ferroud, D.; Schio, L.; Klich, M.; Dupuis-
Hamelin, C.; Mauvais, P.; Lassaigne, P.; Bonnefoy, A.;
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8. Ali, J. A.; Jackson, A. P.; Howells, A. J.; Maxwell, A.
Biochemistry 1993, 32, 2717.
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Consequently, a crude mixture containing both the ani-
line product and aminocoumarin 9 wastreated with
either 3-azido or 4-azidobenzoic acid to furnish the de-
sired amides 10 or 13, respectively. During the total syn-
thesis of novobiocin by Vaterlaus et al., the cyclic
carbonate of novobiocin wastreated with liquid ammo-
nia to produce a 3:1 mixture of carbamateswith a com-
bined yield of 33%.50 To optimize the amount of
carbamate produced by ammoniaolysis of the similar
carbonate in our system, a number of conditions were
explored. After careful optimization, we found the cyclic
carbonate could be opened with methanolic ammonia at
room temperature to provide the desired 3-carbamate
noviose products, 1151 and 1452 in good yieldsand with
good regioselectivity (Scheme 2). 2-Carbamate products
(12 and 15) were also isolated in small quantities.
13. Jackson, A. P.; Maxwell, A.; Wigley, D. B. J. Mol. Biol.
1991, 217, 15.
14. Tsai, F. T. F.; Singh, O. M. P.; Skarzynski, T.; Wonacott,
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In this letter, we described the syntheses of four photo-
labile analoguesof novobiocin, an inhibitor of not
only type II topoisomerases, but also Hsp90. These
photolabile analoguesare currently under biological
investigation for their ability to covalently modify the
C-terminal ATP binding site of Hsp90. The outcome
of these studies will be reported in due course.
25. Agatsuma, T.; Ogawa, H.; Akasaka, K.; Asai, A.;
Yamashita, Y.; Mizukami, T.; Akinaga, S.; Saitoh, Y.
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Acknowledgements
The authorsgratefully acknowledge support of thispro-
ject by the NIH COBRE RR017708 and The University
of Kansas Center for Research. G.S. is the recipient of a
Susan G. Komen Breast Cancer Foundation Disserta-
tion Award.
27. Cardenas, M. E.; Sanfridson, A.; Cutler, S. N.; Heitman,
J. Trends Biotechnol. 1998, 16, 427.
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