986
K. Tatsuta et al. / Tetrahedron Letters 52 (2011) 983–986
Chemical Wisdom’, and the Ministry of Education, Culture, Sports,
Science and Technology (MEXT).
10.5 Hz
19ax. 19eq.
H
H
6.7%
H
OH
19
O
15
Me
Me
OH
O
17
Supplementary data
OH
1
O
O
H
H
coupling constant
nOe
Supplementary data (the spectrum data of compounds 3, ent-3,
4, 5, ent-5, 13, 15, 16, 17, ent-17, 18, (1R, 17R)-2, (1R, 17S)-2, (1S,
17R)-2, and (1S, 17S)-2, and 1H NMR spectra (600 MHz in CDCl3)
O
11.2%
of synthetic K1115 B1 , synthetic K1115 B1b, and natural K1115
a
B1s, as well as Table 1, which showed the antibacterial activities
of four compounds ((1R, 17R)-2, (1R, 17S)-2, (1S, 17R)-2, and (1S,
17S)-2)) associated with this article can be found, in the online
References and notes
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Kokai Tokkyo Koho, 1997, JP 09241257.
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51, 545–552.
5. (a) Koizumi, F.; Hasegawa, A.; Yoshida, M.; Matsuda, Y.; Nakanishi, S. J. Antibiot.
2004, 57, 289–290; (b) Koizumi, F.; Hasegawa, A.; Ochiai, K.; Ando, K.; Kondo,
H.; Yoshida, M.; Matsuda, Y.; Nakanishi, S. J. Antibiot. 2003, 56, 985–992; (c)
Potterat, O.; Zähner, H.; Volkmann, C.; Zeeck, A. J. Antibiot. 1993, 46, 346–349.
6. (a) Tatsuta, K.; Hosokawa, S. Sci. Technol. Adv. Mater. 2006, 7, 397–410; (b)
Tatsuta, K.; Hosokawa, S. Chem. Rev. 2005, 105, 4707–4729.
7. (a) Tatsuta, K.; Akimoto, K.; Annaka, M.; Ohno, Y.; Kinoshita, M. Bull. Chem. Soc.
Jpn. 1985, 58, 1699–1706; (b) Tatsuta, K.; Akimoto, K.; Annaka, M.; Ohno, Y.;
Kinoshita, M. J. Antibiot. 1985, 38, 680–682.
8. (a) Tatsuta, K.; Ozeki, H.; Yamaguchi, M.; Tanaka, M.; Okui, T. Tetrahedron Lett.
1990, 31, 5495–5498; (b) Tatsuta, K.; Ozeki, H.; Yamaguchi, M.; Tanaka, M.;
Okui, T.; Nakata, M. J. Antibiot. 1991, 44, 901–902.
9. (a) Tatsuta, K.; Yamazaki, T.; Mase, T.; Yoshimoto, T. Tetrahedron Lett. 1998, 39,
1771–1772; (b) Tatsuta, K.; Yamazaki, T.; Yoshimoto, T. J. Antibiot. 1998, 51,
383–386.
Figure 2. 1H NMR spectrum of the equatorial-H19 of (A) natural K1115 B1s, (B) (1R,
17S)-2, and (C) (1R, 17R)-2.
would originate in the different modes of acetalization with meso-
erythritol and attachment of the 1,3-dioxane to prealnumycin.
We next examined the bioactivities of four compounds includ-
ing (1R, 17R)-2, (1R, 17S)-2, (1S, 17R)-2, and (1S, 17S)-2.22 Interest-
ingly, all compounds showed almost the same antibacterial
activities against Gram positive bacteria.
10. Tatsuta, K.; Hirabayashi, T.; Kojima, M.; Suzuki, Y.; Ogura, T. J. Antibiot. 2004,
57, 291–297.
In conclusion, we have achieved the first total synthesis and
11. Tatsuta, K.; Suzuki, Y.; Toriumi, T.; Furuya, Y.; Hosokawa, S. Tetrahedron Lett.
2007, 48, 8018–8021.
structural determination of K1115 B1 and K1115 B1b (2). Four iso-
a
mers of 2 including (1R, 17R)-2, (1R, 17S)-2, (1S, 17R)-2, and (1S,
12. Mal, D.; Pahari, P. Chem. Rev. 2007, 107, 1892–1918.
13. Torii, S.; Inokuchi, T.; Masatsugu, Y. Bull. Chem. Soc. Jpn. 1985, 58, 3629–3630.
14. Ono, M.; Saotome, C.; Akita, H. Heterocycles 1999, 51, 1503–1508.
15. Buchanan, M. S.; Hashimoto, T.; Takaoka, S.; Asakawa, Y. Phytochemistry 1995,
40, 1251–1257.
17S)-2 were synthesized. By comparison of the 1H NMR spectra
and the optical rotation, the absolute structure of K1115 B1 and
a
K1115 B1b were determined to be (1R, 17S)- and (1R, 17R)-config-
uration, respectively. Alnumycin may have been a mixture of (1R,
17R)- and (1S, 17R)-2 or (1S, 17S)- and (1R, 17S)-2.
16. Magnus, P.; Eisenbeis, S. A.; Magnus, N. A. J. Chem. Soc., Chem. Commun. 1994,
1545–1546.
17. For preparation of 5 and ent-5, see Supplementary data.
18. 1H and 13C NMR spectra of the natural product were provided by Eisai Co., Ltd.
19. The ratio of the diastereomers was determined by comparing the integration
values of 1H NMR at C10-OH (the proton of the phenol in hydrogen bonding) as
well as the equatorial-H19.
Acknowledgments
Authors thank Eisai Co., Ltd for giving NMR spectra of the
natural product and Streptomyces griseorubiginosus (Mer-K1115)
strain. Authors also thank Dr. Yoshikazu Takahashi of Microbial
Chemistry Research Center for fermentation of the strain. Addi-
tionally, authors thanks Mr. Hiroomi Ogino, Mr. Tatsuya Nakamura,
and Dr. Yoshikazu Suzuki for the preliminary studies. Authors are
grateful for financial support to GCOE program ‘Center for Practical
20. Optical rotation; (1R, 17R)-2: ½a D25
ꢁ
+1100° (c 0.10, MeOH), (1R, 17S)-2: ½a D25
ꢁ
+1000° (c 0.14, MeOH), (1S, 17R)-2: ½a D25
ꢀ900° (c 0.10, MeOH), (1S, 17S)-2:
ꢁ
½ ꢁ ꢀ900° (c 0.13, MeOH). Variation in the number is due to the color of the
a 2D5
samples. Each solution of
2
was red. The optical rotation of the natural
product(s) was ½a D27
ꢁ
+1000° (c 0.1, MeOH).
21. Oja, T.; Palmu, K.; Lehmussola, H.; Leppäranta, O.; Hännikäinen, K.; Niemi, J.;
Mäntsätä, P.; Metsä-Ketelä, M. Chem. Biol. 2008, 15, 1046–1057.
22. See Table 1 in Supplementary data.