D. Labrecque et al. / Tetrahedron Letters 42 (2001) 2645–2648
2647
,
Scheme 4. (a) 1. TPAP, NMO, CH2Cl2, 4 A mol. sieves, rt, 30 min; 2. TIPSCl, DIPEA, DMAP, DMF, 70°C, 1 h; (b) 14,
TMSOTf (0.5 equiv.), ClCH2CH2Cl, rt, 2 h then NaHCO3 work-up (38% from 11); (c) NaH 60%, PhCF3, 60°C, 4.5 h (48%); (d)
TBAF, THF, rt, 1 h (70% for 17a18a and 76% for 17b18b); (e) TBAF, HMPA, THF, 40°C, 48 h (52% of a 1:1 mixture of
1 and 2 for 18a and 35% of a 1:2 mixture of 1 and 2 for 18b).
Treatment of 17a or 17b under such conditions (TBAF
in THF) afforded 18a or 18b, respectively. Removal of
the remaining silyl group required more drastic condi-
tions (TBAF in THF–HMPA at 40°C for 48 hours)
which caused isomerization of the enamide double
bond. Therefore, reaction of pure isomers 18a or 18b
both provided mixtures of 1 and 2. Direct formation of
the mixture of 1 and 2 from unseparated 17a and 17b
using these conditions gave lower yields. The two iso-
mers were separated by HPLC and their spectroscopic
characteristics were in agreement with those reported
for the natural products1 except for optical rotation
which was of the same magnitude but of opposite
sign.14 These results suggested that the absolute
configuration of the products as described previously
was incorrect and that the structures of natural (−)-sal-
icylihalamides A and B should be represented by 19
and 201,3 respectively. Therefore, using the same syn-
thetic sequence and starting from the enantiomer of 3,
we have prepared the natural compounds 19 and 20.14
Biological profiles of the presented compounds as well
as closely related analogues will be reported in due
course.
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Acknowledgements
We would like to thank Mrs. Nola Lee and the analyt-
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helpful input into the project.
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