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OH
OMOM
CO
2
Me
CO
2
Me
O
OHC
O
10
15
PPh
3
Br
1,6-hexanediol
PMBO
16
OTHP
O
CH
O
( )
5
PMBO
CO
2
Me
( )
5
PMBO
OMOM
OMOM
O
17
18
14
O
I
tonkinecin
( )
5
OMOM
O
19
Scheme 10-7. Improved synthesis of tokinecin by Wu et al.
three steps. After hydroxyl group protection, an aldol condensation with lactal
derivative and in situ lactonization and oxidative cleavage of terminal diol gave
the aldehyde 11. Wittig reaction of 11 with a ylide derived from 12 afforded vinyl
iodide 13. Sonogashira coupling of 13 with THF containing segment 14 established
the whole skeleton, which was finally converted into tonkinecin after selective
reductions and deprotections.
29
One advantage of using ester 10 is that this inter-
mediate can be easily prepared on a large scale; it is of great value as a common
building block for the synthesis of other acetogenins.
We later published an improved synthesis of tonkinecin
30
because of the low
yield of the coupling reaction between 11 and 12 (only 30% previously) in a pre-
vious study. One major reason is that the vinyl iodide 12 was not stable enough to
survive the basic reaction conditions. An alternative for the synthesis of right-side
segment was then designed, in which the vinyl iodide functionality was introduced
in the last step to avoid those basic conditions (Scheme 10-7). The Wittig reaction
of aldehyde 15 with 16 and subsequent hydrogenation afforded ester 17, which was
converted to lactone 18 by aldol reaction with lactal followed by acid treatment and
b-elimination. Selective deprotection, Dess-Martin oxidation, and Takai reaction
(to introduce the vinyl iodide) afforded the precursor 19. Similar treatments of
19 with 14, as well as subsequent intermediates as described previously, finally pro-
vided tonkinecin.
Corossolin was isolated by a French group in 1991, and the absolute configura-
tion of its C-10 hydroxyl group remained unknown until its total synthesis was
achieved by us in 1999 (Scheme 10-8).
31
The first total synthesis of corossolin
was achieved in 1996 by Makabe et al. in Japan.
34
However, the specific rotations
and nuclear magnetic resonances (NMRs) of their two synthetic C-10 epimers are
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