Scheme 2 Reagents and conditions: i, 3 M KOH–MeOH–THF (1+2+2), rt 1 h, 87%; ii, TPAP, NMO, MS 4A, CH
MeO) OPCH CO(CH CO Et (12), DBU, LiCl, MeCN, rt, 2.5 h, 79% 2 steps; iv, (R)-BINAl-H, THF, 2100 °C, 6 h, 85% (R+S > 20+1); v, p-TsOH,
benzene, reflux, 0.5 h, 92%; vi, NaHMDS, TMSCl, PhSeBr, THF, 278 °C, 4 h, 94%; vii, H , NaHCO , AcOEt–THF, rt, 0.5 h, 94%; viii, DDQ, wet
I·I , NaHMDS, HMPA, THF, 2100 to 0 °C, 61% (Z+E = 4+1)
steps; xi, 1 M HCl–MeOH (1+9), rt, 10 h, 89%, xii, (1) TBSOTf, 2,6-lutidine, 278 °C, 10 min, then TESOTf 278 °C to rt (2) separation 56% (Z-isomer);
xiii, 1 M HCl–THF–MeCN (1+3+6), 210 °C, 2 h, 70% (18% recovery of 22); xiv, 24, PdCl (MeCN) , DMF, rt 25 h, 80%; xv, PCl , MPMOH, Py, then
TBHP–CH Cl , 56%; xvi, HF–MeCN, then Py, rt, 20 h, 38%.
2 2
Cl , rt, 1 h; iii,
(
2
2
)
2 3
2
2
2
O
2
3
+
2 2 3 2 2 3 2
CH Cl , rt, 0.5 h, 96%; ix, Dess–Martin periodinane, NaHCO , CH Cl , rt, 1 h; x, Ph P CH
2
2
2
3
2
2
group of 17 was removed by oxidative treatment. The resultant
alcohol 18 was oxidized with Dess–Martin reagent to give
aldehyde 19. Iodomethylenation of 19 by Wittig reaction gave
‡ Geometric isomers of 22 (Z+E = 4+1) were separable at this stage by
chromatography.
§
The compound 23 was the same as that reported by Jacobsen’s group.9
20 with the Z-isomer as a major product. It was essentially
important to remove the acetonide group at this stage, because
all attempts to remove the acetonide group after coupling with
the segment C resulted in failure due to the acid-labile property
of the triene moiety. Therefore, the acetonide group of 20 was
removed by acidic treatment to give 21, with concomitant
removal of the TBS group. In order to introduce a phosphoryl
group regioselectively, the tert-hydroxy group and the sterically
less hindered sec-hydroxy group were selectively protected as
follows. All hydroxy groups of 21 were regioselectively
protected with a tert-butyldimethylsilyl (TBS) group and a
triethylsilyl (TES) group in one pot; then the TES group
attached to the sec-hydroxy group of 22‡ was selectively
removed to give 23.§
1
J. B. Tunac, B. D. Graham and W. E. Dobson, J. Antibiot., 1983, 36,
1595; S. S. Stampwala, R. H. Bunge, T. R. Hurley, N. E. Willmer, A. J.
Brankiewicz, C. E. Steinman, T. A. Smitka and J. C. French, J. Antibiot.,
1983, 36, 1601.
R. C. Jackson, D. W. Fry, T. J. Boritzki, B. J. Roberts, K. E. Hook and
E. R. Leopold, Adv. Enzyme Regul., 1985, 23, 193; R. S. De Jong, E. G.
E. De Vries and N. H. Mulder, Anti-Cancer Drugs, 1997, 8, 413.
R. S. De Jong, N. H. Mulder, D. R. A. Uges, D. Th. Sleijfer, F. J. P.
Höppener, H. J. M. Groen, P. H. B. Willemse, W. T. A. van der Graaf
and E. G. E. De Vries, Br. J. Cancer, 1999, 79, 882.
2
3
4
T. J. Boritzki, T. S. Wolfard, J. A. Besserer, R. C. Jackson and D. W.
Fry, Biochem. Pharmacol., 1988, 37, 4063.
5 T. S. Ingebritsen and P. Cohen, Eur. J. Biochem., 1983, 132, 255; P.
Cohen, Annu. Rev. Biochem., 1989, 58, 453.
6
D. L. Boger, M. Hikota and B. M. Lewis, J. Org. Chem., 1997, 62,
1748.
G. Just and B. O’Connor, Tetrahedron Lett., 1988, 29, 753; T. Esumi, N.
Okamoto, Y. Iwabuchi and S. Hatakeyama, Tennenn Yuki Kagobutsu
Toronkai Koen Yoshishu, 2000, 42nd, 643; [CA, 134:326296]; S. Y.
Liu, D. F. Huang, H. H. Hong and L. Huang, Chin. Chem. Lett., 2000,
Organotin compound 24 corresponding to the segment C,
15
prepared according to a literature procedure, was coupled with
7
2
3 under Pd(0)-catalyzed conditions to give 25 in good yield,
which was phosphorylated to give fully protected fostriecin 26.
1
Deprotection by fluoride-treatment gave fostriecin (1), the H
NMR data and chromatographic property of which were
identical to those of natural fostriecin.
1
1, 957; [CA, 134:115778]; J. Cossy, F. Pradaux and S. BouzBouz, Org.
Lett., 2001, 3, 2233.
In conclusion, a convergent synthesis of fostriecin (1) was
achieved, which would be of great use for the synthesis of
various fostriecin congeners to obtain a stable analog of
fostriecin, and to clarify the mechanism of its biological
activity. Synthesis of fostriecin analogs according to the present
strategy is in progress in our laboratory.
We thank Dr R. J. Schultz of the Drug Synthesis and
Chemistry Branch, Developmental Therapeutics Program, Di-
vision of Cancer Treatment and Diagnosis, National Cancer
Institute, for a sample of natural fostriecin (1).
8 D. L. Boger, S. Ichikawa and W. Zhong, J. Am. Chem. Soc., 2001, 123,
4161.
9
D. E. Chavez and E. N. Jacobsen, Angew. Chem., Int. Ed., 2001, 40,
3
667.
1
0 K. Mori, T. Takigawa and T. Matsuo, Tetrahedron, 1979, 35, 933; A. B.
Smith III, S. S.-Y. Chen, F. C. Nelson, J. M. Reichert and B. A.
Salvatore, J. Am. Chem. Soc., 1997, 119, 10935.
1
1 H. C. Kolb, M. S. VanNieuwenhze and K. B. Sharpless, Chem. Rev.,
1
994, 94, 2483.
12 S. Vijayasaradhi, J. Singh and I. S. Aidhen, Synlett, 2000, 110.
13 E. Wenkert, M. Guo, R. Lavilla, B. Porter, K. Ramachandran and J.-H.
Sheu, J. Org. Chem., 1990, 55, 6203.
1
4 R. Noyori, I. Tomino, Y. Tanimoto and M. Nishizawa, J. Am. Chem.
Soc., 1984, 106, 6709; R. Noyori, I. Tomono, M. Yamada and M.
Nishizawa, J. Am. Chem. Soc., 1984, 106, 6717.
Notes and references
†
To the best of our knowledge, one study by Hatakeyama’s group at
Nagasaki University has been orally presented recently in Japan: T. Esumi,
N. Okamoto, Y. Iwabuchi and S. Hatakeyama, Symposium on Progress in
Organic Reaction and Synthesis, Abstract, 2001, 27th, 202.
15 Synthesis of the compound having a TBS group in place of the TBDPS
group of 22 has been reported: A. K. Mapp and C. H. Heathcock, J. Org.
Chem., 1999, 64, 23.
CHEM. COMMUN., 2002, 742–743
743