ORGANIC
LETTERS
2012
Vol. 14, No. 23
5896–5899
Chiral Pool Based Efficient Synthesis
of the Aminocyclitol Core and Furanoside
of (ꢀ)- Hygromycin A: Formal Total
Synthesis of (ꢀ)-Hygromycin A
Hong-Jay Lo, Yuan-Kang Chang, and Tu-Hsin Yan*
Department of Chemistry, National Chung-Hsing University, Taichung 400, Taiwan,
Republic of China
Received October 14, 2012
ABSTRACT
A chiral pool based synthetic strategy that leads from the readily available and inexpensive C2-symmetric tartaric acids to the chiral O-isopropyli-
denebenzooxazole;a convenient precursor to the aminocyclitol core of hygromycin A as well as the chiral γ-disilyloxybutyrolactone;a pivotal
intermediate to approach to the furanoside of hygromycin A.
The natural product hygromycin A 1 was shown to have
a relatively broad spectrum of activity such as activity
against Gram-positive and Gram-negative bacterial and
high hemaglutination inactivation activity and high
antiterponemal activity (Figure 1).1 In addition, the amino-
cyclitol core 2 of hygromycin A has also attracted interest
since the discovery that the aminocyclitol unit 2 is critical
for the activity of this class of compounds while the
furanoside part was not.2 Despite the promising biological
activities and interesting unique structure of hygromycin
A, there have been few reports on the synthesis of the
structural components of hygromycin A,3ꢀ5 only two
reports on the total synthesis of hygromycin A, by
(1) (a) Pittenberger, R. C.; Wolfe, R. N.; Hohen, M. M.; Marks,
P. N.; Daily, W. A.; McGuire, M. Antibiot. Chemother. 1953, 3, 1268. (b)
Mann, R. L.; Gale, R. M.; VanAbeele, F. R. Antibiot. Chemother. 1953,
3, 1279. (c) Sumiki, Y.; Nakamura, G.; Kawasaki, M.; Yamashita, S.;
Anazi, K.; Isono, K.; Serizawa, Y.; Tomiyama, Y.; Suzuki, S. J. Antibiot.
Ser. A 1955, 8, 170. (d) Isono, K.; Yamashita, S.; Tomiyama, Y.; Suzuki,
S. J. Antibiot. 1957, 10, 21. (e) Wakisaka, Y.; Koizumi, K.; Nishimoto,
Y.; Kobayashi, M.; Tsuji, N. J. Antibiot. 1980, 33, 695.
(2) Hecker, S. J.; Minich, M. L.; Werner, K. M. Bioorg. Med. Chem.
Lett. 1992, 2, 533. Hecker, S. J.; Lilley, S. C.; Minich, M. L.; Werner,
K. M. Bioorg. Med. Chem. Lett. 1992, 2, 1015. Hecker, S. J.; Lilley, S. C.;
Werner, K. M. Bioorg. Med. Chem. Lett. 1992, 2, 1043. Hecker, S. J.;
Cooper, C. B.; Blair, K. T.; Lilley, S. C.; Minich, M. L.; Werner, K. M.
Bioorg. Med. Chem. Lett. 1993, 3, 289. James, B. H.; Elliott, N. C.;
Jefson, M. R.; Koss, D. A.; Schicho, D. L. J. Org. Chem. 1994, 59, 1224.
Cooper, C. B.; Blair, K. T.; Jones, C. S.; Minich, M. L. Bioorg. Med.
Chem. Lett. 1997, 7, 1747.
(3) (a) Donohoe, T. J.; Flores, A.; Bataille, C. J. R.; Churruca, F.
Angew. Chem., Int. Ed. Engl. 2009, 48, 6507. (b) Chida, N.; Ohtsuka, M.;
Nakazawa, K.; Ogawa, S. J. Chem. Soc., Chem. Commun. 1989, 436. (c)
Chida, N.; Ohtsuka, M.; Nakazawa, K.; Ogawa, S. J. Org. Chem. 1991,
56, 2976.
(4) (a) Trost, B. M.; Dudash, J.; Dirat, O. Chem., Eur. J 2002, 8, 259.
(b) Trost, B. M.; Dudash, J.; Hembre, E. J. Chem., Eur. J. 2001, 7, 1619.
(5) (a) Donohoe, T. J.; Johnson, P. D.; Pye, R. J.; Keenan, M. Org.
Lett. 2005, 7, 1275. (b) Arjona, O.; deDios, A.; Plumet, J.; Saez, B.
J. Org. Chem. 1995, 60, 4932. (c) Gurale, B. P.; Shashidhar, M. S.;
Gonnade, R. G. J. Org. Chem. 2012, 77, 5801.
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10.1021/ol3028237
Published on Web 11/13/2012
2012 American Chemical Society