M. Sasaki et al. / Tetrahedron Letters 44 (2003) 6199–6201
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and Technology Corporation (JST) and Suntory Insti-
tute for Bioorganic Research (SUNBOR).
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Scheme 4. Reagents and conditions: (a) 10, n-BuLi, THF, rt,
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steps); (e) BF3·OEt2, Me2S, CH2Cl2, 0°C, 87%; (f) Hg(ClO4)2,
CaCO3, THF/MeOH (4:1), 0°C; (g) PPTS, MeOH, rt, 85%
(two steps); (h) Ph3P, THF, then H2O, rt; (i) Boc2O, Et3N,
CH2Cl2, rt, quant. (two steps); (j) Yb(OTf)3, CH3CN, −20°C,
57%; (k) LiDBB, THF, −78°C, 92%; (l) AcCl, 2,4,6-collidine,
CH2Cl2, −40°C, 79%; (m) TESOTf, 2,6-lutidine, CH2Cl2,
−40°C, 86%; (n) DIBALH, CH2Cl2, −78°C, 88%; (o) TPAP,
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that of synthetic ent-6a ([h]2D0 +4.6 (c 0.22, CH2Cl2)3f; [h]2D3
+5 (c 0.26, CHCl3)3g), we determined to synthesize com-
pound 6a in the present study.
,
NMO, 4 A MS, CH2Cl2, rt, 91%; (p) 31, MgBr2·OEt2,
,
CH2Cl2, −20°Crt, 78%; (q) TPAP, NMO, 4 A MS, CH2Cl2,
rt, 73%; (r) HF·pyr, pyr, THF, 0°Crt, 30%.
clo[3.3.1]nonane ring system to complete the synthesis
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in 30% yield (not optimized). The spectral data for 6a
were fully consistent with those reported previously.3f
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In conclusion, we have developed a convergent syn-
thetic route to the FGHI ring system 6a of azaspiracids
based on dithiane anion–epoxide coupling for the C35–
C36 bond construction. Further studies toward the
total synthesis of azaspiracids are currently underway
and will be reported in due course.
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We are most grateful to Professor K. Tachibana (The
University of Tokyo) for helpful discussions. We also
thank Professor M. Satake (Tohoku University) for
valuable information and Dr. Y. Hirose (Amano Phar-
maceutical Co.) for the kind gift of lipases. This work
was financially supported by CREST, Japan Science