P. J. Krenitsky, D. L. Boger / Tetrahedron Letters 43 (2002) 407–410
409
An alternative Cu(OAc)2-promoted16 closure of the
boronic acid 10 was also examined (3 equiv. Cu(OAc)2,
5 equiv. of pyridine or collidine, 1 mM CH2Cl2, 25°C,
5 days) and found to be less successful, providing low
conversions to 9 (9%) and a mixture of the correspond-
ing acyclic phenol or phenylalanine derivatives derived
from oxidation or reduction of the boronic acid (Eq.
(1)).
Am. Chem. Soc. 1991, 113, 1427–1429; (d) Boger, D. L.;
Yohannes, D.; Zhou, J.; Patane, M. A. J. Am. Chem.
Soc. 1993, 115, 3420–3430; (e) Boger, D. L.; Patane, M.
A.; Zhou, J. J. Am. Chem. Soc. 1994, 116, 8544–8556; (f)
Bigot, A.; Dau, M. E.; Tran, H.; Zhu, J. J. Org. Chem.
1999, 64, 6283–6296.
5. Helynck, G.; Dubertret, C.; Frechet, D.; Leboul, J. J.
Antibiot. 1998, 51, 512–514.
6. (a) Boger, D. L.; Yohannes, D. J. Org. Chem. 1991, 56,
1763–1767; (b) Boger, D. L.; Borzilleri, R. M. Bioorg.
Med. Chem. Lett. 1995, 5, 1187–1190; (c) Boger, D. L.;
Zhou, J.; Borzilleri, R. M.; Nukui, S. Bioorg. Med. Chem.
Lett. 1996, 6, 1089–1092; (d) Inoue, T.; Sasaki, T.;
Takayanagi, H.; Harigaya, Y.; Hoshino, O.; Hara, H.;
Inaba, T. J. Org. Chem. 1996, 61, 3936–3937; (e) Boger,
D. L.; Zhou, J. J. Org. Chem. 1996, 61, 3938–3939; (f)
Boger, D. L.; Zhou, J.; Borzilleri, R. M.; Nukui, S.;
Castle, S. L. J. Org. Chem. 1997, 62, 2054–2069; (g)
Bigot, A.; Beugelmans, R.; Zhu, J. Tetrahedron 1997, 53,
10753–10764.
OMe
Br
OH
O
B(OH)2
9
(1)
N
H
CO2Me
NH
Cbz
10
7. Reviews: (a) Evans, D. A.; DeVries, K. M. In Glycopep-
tide Antibiotics; Nagarajan, R., Ed.; Marcel Dekker: New
York; 1994, pp. 3–103; (b) Rao, A. V. R.; Gurjar, M. K.;
Reddy, K. L.; Rao, A. S. Chem. Rev. 1995, 95, 2135–
2167; (c) Nicolaou, K. C.; Boddy, C. N. C.; Brase, S.;
Winssinger, N. Angew. Chem., Int. Ed. 1999, 38, 2097–
2152; (d) Boger, D. L. Med. Chem. Rev. 2001, 21, 356–
381.
8. Preparation of the AB ring system: Boisnard, S.; Car-
bonelle, A.-C.; Zhu, J. Org. Lett. 2001, 3, 2061–2064.
9. Boger, D. L.; Yohannes, D. J. Org. Chem. 1987, 52,
5283–5286.
In conclusion, the L,L-isomer of a fully functionalized
BC ring system of RP 66453, which constitutes an
unusual reversed 14-membered cycloisodityrosine, has
been assembled through use of a key diaryl ether
macrocyclization reaction enlisting a phenoxide nucleo-
philic aromatic substitution reaction of an o-fluoroni-
troaromatic. Extension of this work in the total synthe-
sis of RP 66453 is in progress and will be disclosed in
due course.
10. Carren˜o, M. C.; Ruano, J. L. G.; Sanz, G.; Toledo, M.
A.; Urbano, A. Synlett 1997, 1241–1242.
Acknowledgements
11. Bois-Choussy, M.; Neuville, L.; Beugelmans, R.; Zhu, J.
J. Org. Chem. 1996, 61, 9309–9322.
We gratefully acknowledge the financial support of the
National Institute of Health (CA41101) and The
Skaggs Institute of Chemical Biology. P.J.K. is a
Skaggs Fellow.
1
12. For 7: [h]2D5 +23 (c 0.08, CHCl3); H NMR (CDCl3, 500
MHz) l 7.74 (d, 1H, J=5.9 Hz), 7.32 (m, 6H), 7.10 (dd,
1H, J=8.6, 10.5 Hz), 6.85 (d, 1H, J=1.9 Hz), 6.73 (s,
1H), 6.72 (s, 1H), 6.44 (s, 1H), 5.54 (d, 1H, J=7.7 Hz),
5.07 (dd, 2H, J=12.3, 22.2 Hz), 4.78 (dd, 1H, J=6.2,
12.8 Hz), 4.38 (d, 1H, J=7.0 Hz), 3.83 (s, 3H), 3.71 (s,
3H), 3.15 (m, 1H), 3.02 (dd, 1H, J=6.1, 13.7 Hz), 2.89
(m, 2H); 13C NMR (CDCl3, 125 MHz) l 171.0, 170.9,
155.8, 153.7, 150.4, 143.9, 137.1, 136.7, 136.1, 134.3,
133.2, 128.8, 128.5, 128.2, 126.8, 125.1, 118.6, 116.4,
116.2, 67.5, 61.1, 56.3, 53.2, 53.0, 37.6, 37.0; IR (film)
wmax 3311, 3065, 2952, 1652, 1538, 1435, 1351, 1251, 993,
842 cm−1; MALDIFTMS (DHB) m/z 670.0791 (M++Na,
C28H27BrFN3O9 requires 670.0807).
References
1. (a) Kaneda, M.; Tamai, S.; Nakamura, S.; Hirata, T.;
Kushi, Y.; Suga, T. J. Antibiot. 1982, 35, 1137–1140.
Total synthesis: (b) Boger, D. L.; Zhou, J. J. Am. Chem.
Soc. 1993, 115, 11426–11433; (c) Nishiyama, S.; Naka-
mura, K.; Suzuki, Y.; Yamamura, S. Tetrahedron Lett.
1986, 27, 4481–4484.
2. Jolad, S. D.; Hoffmann, J. J.; Torrance, S. J.; Wiedhopf,
R. M.; Cole, J. R.; Arora, S. K.; Bates, R. B.; Gargiulo,
R. L.; Kriek, G. R. J. Am. Chem. Soc. 1977, 99, 8040–
8044.
3. Itokawa, H.; Takeya, K.; Mori, N.; Sonobe, T.; Mihashi,
S.; Hamanaka, T. Chem. Pharm. Bull. 1986, 34, 3762–
3768.
4. Total syntheses: (a) Inaba, T.; Umezawa, I.; Yuasa, M.;
Inoue, T.; Mihashi, S.; Itokawa, H.; Ogura, K. J. Org.
Chem. 1987, 52, 2957–2958; (b) Inoue, T.; Inaba, T.;
Umezawa, I.; Yuasa, M.; Itokawa, H.; Ogura, K.;
Komatsu, K.; Hara, H.; Hoshino, O. Chem. Pharm. Bull.
1995, 43, 1325–1335; (c) Boger, D. L.; Yohannes, D. J.
13. For 8: 1H NMR (CDCl3, 400 MHz) l 8.10 (d, 1H, J=1.8
Hz), 7.66 (dd, 1H, J=2.2, 8.4 Hz), 7.44–7.32 (m, 13H),
7.00–6.88 (m, 4H), 6.81 (d, 1H, J=9.7 Hz), 5.25–5.16 (m,
2H), 5.12–4.93 (m, 5H), 4.87–4.77 (m, 2H), 4.63–4.57 (m,
1H), 5.54–4.47 (m, 1H), 4.24 (bs, 1H), 4.06 (s, 3H), 4.04
(s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.65–3.52 (m, 4H),
2.69–2.46 (m, 4H); 13C NMR (CDCl3, 100 MHz) l 171.5,
171.2, 155.6, 154.4, 150.0, 145.0, 144.9, 144.6, 138.0,
136.3, 135.8, 135.5, 134.8, 132.7, 132.3, 128.9, 128.7,
128.5, 128.2, 128.1, 127.7, 126.1, 118.3, 118.0, 114.6, 67.8,
67.5, 61.5, 61.2, 53.5, 52.9, 52.6, 37.8, 32.8, 29.6; IR (film)
wmax 3350, 2942, 1738, 1682, 1532, 1494, 1353, 1279, 1223,