COMMUNICATIONS
[9] a) H. Tohma, S. Takizawa, H. Watanabe, Y. Kita, Tetrahedron Lett.
1998, 39, 4547 ± 4550; b) H. Tohma, S. Takizawa, H. Watanabe, Y.
Fukuoka, T. Maegawa, Y. Kita, J. Org. Chem. 1999, 64, 3519 ± 3523.
[10] The effects of halide ions have been reported by several groups: a) T.
Shono, Y. Matsumura, J. Hayashi, M. Mizoguchi, Tetrahedron Lett.
1979, 165 ± 168; b) S. D. Rychnovsky, R. Vaidyanathan, J. Org. Chem.
1999, 64, 310 ± 312; c) J. H. Espenson, Z. Zhu, T. H. Zauche, J. Org.
Chem. 1999, 64, 1191 ± 1196.
[11] a) N. Goudarzian, P. Ghahramani, S. Hossini, Polym. Int. 1996, 39,
61 ± 62; b) R. A. Lee, D. S. Donald, Tetrahedron Lett. 1997, 38, 3857 ±
3860; c) B. Hinzen, S. V. Ley, J. Chem. Soc. Perkin Trans. 1 1997, 1907 ±
1908; d) J. M. Harris, Y. Liu, S. Chai, M. D. Andrews, J. C. Vederas, J.
Org. Chem. 1998, 63, 2407 ± 2409; e) S. Abraham, P. K. Rajan, K.
Sreekumar, Polym. Int. 1998, 45, 271 ± 277; f) J. Habermann, S. V. Ley,
J. S. Scott, J. Chem. Soc. Perkin Trans. 1 1999, 1253 ± 1255.
[12] H. Togo, G. Nogami, M. Yokoyama, Synlett 1998, 534 ± 536.
[13] a) S. V. Ley, A. W. Thomas, H. Finch, J. Chem. Soc. Perkin Trans. 1
1999, 669 ± 671; b) S. V. Ley, O. Schucht, A. W. Thomas, P. J. Murray, J.
Chem. Soc. Perkin Trans. 1 1999, 1251 ± 1252. They obtained benzal-
dehyde quantitatively, however, only a trace amount of 2e was
obtained even after 48 h under their reaction conditions (PSDIB in
CH2Cl2).
[14] PSDIB was prepared from polystyrene standard (Mw 44000)
(Aldrich) via poly(iodostyrene) (78% iodinated) following known
procedures. Elemental analysis (C 45.86, H 3.93, I 37.41) revealed the
resin loading to be 2.0 mmolg 1, which indicated that 68% of the
iodophenyl rings in the resin was converted into (diacetoxyiodo)-
phenyl rings: Y. Yamada, M. Okawara, Makromol. Chem. 1972, 152,
153 ± 162.
[15] J. J. Parlow, B. L. Case, M. S. South, Tetrahedron 1999, 55, 6785 ± 6796.
[16] Intermolecular homoesterification mainly proceeds to give
Ph(CH2)3OCO(CH2)2Ph (51%) in the absence of NaHCO3 (2k:
38%).
of a variety of sluggishly reactive and/or sparsely soluble
hypervalent iodine reagents in water under neutral conditions.
Further studies on the application of this system are now in
progress.
Experimental Section
Method A (for primary alcohols): PhI O (0.44 mmol; Tokyo Chemical
Industry Co., Ltd.) was added at room temperature to a stirred mixture of 1
(0.20 mmol) and KBr (0.04 mmol) in water (1.0 mL), and the mixture was
stirred for 2 h. The resulting mixture was extracted with AcOEt, washed
with brine, dried over Na2SO4, evaporated in vacuo, and the residue was
purified by column chromatography (EtOAc/n-hexane) to give pure 2.
Intermolecular esterification through nucleophilic attack on the initially
formed aldehyde also proceeds under the conditions of Method B.
Method B (for secondary alcohols): Water (2.0 mmol) was added dropwise
to a stirred mixture of 1 (0.2 mmol), PhI O (0.22 mmol), and KBr
(0.2 mmol). The mixture was stirred or sonicated for several hours while
checking the reaction progress by gas or thin-layer chromatography. After
completion, n-hexane was added to the mixture, and then filtered.
Evaporation of the solvent under vacuum afforded a crude product that
was further purified by column chromatography (Et2O/n-hexane) to give
pure 2.
Method C (for the oxidation with PSDIB): PSDIB (22 mmol), used without
any pretreatment, was added at room temperature to a stirred suspension
of 1 (20 mmol) and KBr (14 mmol) in water (40 mL), and the mixture was
then sonicated for several hours. The resulting mixture was filtered and the
residue containing 2 was washed with water to remove KBr, then extracted
with n-hexane or MeOH, and the filtrate was evaporated to give 2. The
product was purified by column chromatography, when necessary.
[17] Even after stirring PSDIB in water for 4 d, the addition of 1e and KBr
to this suspension gave 2e in 68% yield.
Received: September 21, 1999 [Z14040]
[18] 2e was obtained only in 8% yield, when the reaction was performed
with PSDIB in CH2Cl2 (containing 4- molecular sieves) in the
presence of 20 mol% NEt4Br as a bromide ion source. However,
addition of a catalytic amount of water to the above mentioned
mixture enhanced the yield of 2e to 51%.
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2564 ± 2566, and references therein.
[2] Recent reviews, see a) P. J. Stang, V. V. Zhdankin, Chem. Rev. 1996,
96, 1123 ± 1178; b) A. Varvoglis, Hypervalent Iodine in Organic
Synthesis, Academic Press, San Diego, 1997; c) T. Kitamura, Y.
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Hirt, Synthesis 1999, 1271 ± 1287.
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Lett. 1995, 36, 3485 ± 3488.
Total Synthesis of ()-Concanamycin F**
Ian Paterson,* Victoria A. Doughty,
Malcolm D. McLeod, and Thomas Trieselmann
The concanamycin group of macrolides, first isolated from a
culture of Streptomyces diastatochromogenes Sp. S45 by
Kinashi and co-workers and typified by concanamycin A (1,
Figure 1)[1a±d] and its aglycone, concanamycin F 2),[1e,f] exhibit
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[6] T. Takaya, H. Enyo, E. Imoto, Bull. Chem. Soc. Jpn. 1968, 41, 1032.
[7] For our recent work, see a) Y. Kita, H. Tohma, K. Hatanaka, T.
Takada, S. Fujita, S. Mitoh, H. Sakurai, S. Oka, J. Am. Chem. Soc.
1994, 116, 3684 ± 3691; b) Y. Kita, M. Arisawa, M. Gyoten, M.
Nakajima, R. Hamada, H. Tohma, T. Takada, J. Org. Chem. 1998,
63, 6625 ± 6633; c) T. Takada, M. Arisawa, M. Gyoten, R. Hamada, H.
Tohma, Y. Kita, J. Org. Chem. 1998, 63, 7698 ± 7706; d) Y. Kita, M. Egi,
T. Takada, H. Tohma, Synthesis 1999, 885 ± 897; e) M. Arisawa, S.
Utsumi, M. Nakajima, N. G. Ramesh, H. Tohma, Y. Kita, Chem.
Commun. 1999, 469 ± 470, and references therein.
potent inhibition of vacuolar (H ) ATPase activity.[2] The
[*] Dr. I. Paterson, V. A. Doughty, M. D. McLeod, T. Trieselmann
University Chemical Laboratory
Lensfield Road, Cambridge, CB2 1EW (UK)
Fax: (44)1223-336362
[**] We thank the EPSRC (GR/K54052), Knoll Pharmaceuticals (CASE
Studentship to V.A.D.), the Cambridge Commonwealth Trust
(M.D.M.), and Merck for support, and Dr R. Norrie (Knoll
Pharmaceuticals) for helpful discussions. We also thank Prof. A.
Zeeck (Göttingen) for kindly providing copies of 1H NMR spectra of
concanamycin F (concanolide A).
[8] a) Organic Synthesis in Water (Ed.: P. A. Grieco), Blackie Academic,
London, 1998; b) Aqueous-Phase Organometallic Catalysis (Eds.: B.
Cornils, W. A. Herrmann), Wiley-VCH, Weinheim, 1998; c) Organic
Reactions in Aqueous Media (Eds.: C.-J. Li, T.-H. Chan), Wiley, New
York, 1997.
1308
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0570-0833/00/3907-1308 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2000, 39, No. 7