X. Z. Zhao et al. / Tetrahedron Letters 46 (2005) 6941–6944
6943
OTBS
SO2Ph
O
S
a
6
7
S
+
TBDPSO
OTBS
OH
O
28
OH
O
HO
OTBS
O
S
S
b
c
O
TBDPSO
H
OTBS
O
5
O
S
HO
S
4
Scheme 4. Reagentsand conditions: (a) nBuLi, THF, ꢀ78 °C, then 6, THF, ꢀ78 °C, 75%; (b) (i) CrO3, Py, CH2Cl2, 0 °C, 74%; (ii) Na–Hg, MeOH,
NaH2PO4, rt, 63%; (c) HF (40%), CH3CN, rt, 35%.
hydroxyl group and deacetalization generated the alde-
Acknowledgments
hyde 6 asa C –C16 fragment of didemnaketals( Scheme
9
2).
We are grateful for the financial support of the Natural
Science Foundation of China (NSFC Nos. 29925205,
30271488, 20021001, 203900501).
Then, we turned to the construction of C17–C23 frag-
ment of didemnaketals( Scheme 3). Conjugative ketone
16 wasprepared from ( R)-pulegone 8 in 56% yield
through five steps.2 Reduction of ketone 16 with NaBH4
followed by protection of the formed hydroxyl group
with TBDPSCl afforded alkene 18. Then, the diol 19
was produced through the stereoselective osmylation7
of the double bond in compound 18. Subsequently,
selective protection of the secondary hydroxyl group in
the diol 19 afforded the intermediate 20. Fortunately,
elimination of the tertiary hydroxyl group in 20, gave
compound 21 with the double bond in six-membered
ring (no other isomer was found). Ozonolysis of 21 pro-
duced the open-chain keto-aldehyde 22. Selective reduc-
tion of the aldehyde group in 22 followed by
thioacetalylation and iodination with iodine afforded
the iodide 25, whose absolute stereochemistry was
conformed by X-ray (Fig. 1). Thisiodide 25 was
converted to the sulfone 26 and deprotection of 26 pro-
duced the diol 27. Protection of the diol 27 with DMP
afforded the sulfone 7 asa C 17–C23 fragment of didem-
naketals.
Supplementary data
Supplementary data associated with this article can be
References and notes
1. (a) Potts, B. C. M.; Faulkner, D. J.; Chan, J. A.; Simolike,
G. C.; Offen, P. M.; Hemling, E.; Francis, T. A. J. Am.
Chem. Soc. 1991, 113, 6321; (b) Pika, J.; Faulkner, D. Nat.
Prod. Lett. 1995, 7, 291.
2. (a) Jia, Y. X.; Wu, B.; Li, X.; Ren, S. K.; Tu, Y. Q.; Chan,
A. S. C.; Kitching, W. Org. Lett. 2001, 3, 847; (b) Jia, Y. X.;
Li, X.; Wu, B.; Zhao, X. Z.; Tu, Y. Q. Tetrahedron 2002,
58, 1697.
3. Salomon, C. E.; Williams, D. H.; Lobkovsky, E.; Clardy,
J. C.; Faulkner, D. J. Org. Lett. 2002, 4, 1699.
4. Zhao, X. Z.; Tu, Y. Q.; Peng, L.; Li, X. Q.; Jia, Y. X.
Tetrahedron Lett. 2004, 45, 3713.
5. The configuration of 11 wasdetermined from itsacetonide
derivative 29. The stereochemistry of 29 wasconformed
The coupling of 6 and 7 wascarried out ashsown in
Scheme 4. Deprotonation of the sulfone 6 with n-BuLi
and subsequent reaction with aldehyde 7 afforded the
a-hydroxy sulfone 28. Subsequently, oxidation of the
1
through H NMR NOE experiment asshown below. For
example, irradiation of C11–H (d: 3.73 ppm) lead to 5%
enhancement of C9–H (d: 1.33 ppm), and 4% enhancement
of C13–H (d: 1.57 ppm), and irradiation of C12–H (d:
3.47 ppm) lead to 5% enhancement of C17–H (d: 1.25 ppm),
and 3% enhancement of C18–H (d: 1.00 ppm).
8
hydroxyl group of 28 with Collinsreagent and then
removal of the sulfone with 6% sodium amalgam gave
compound 5 a single isomer as the open-chain poly-
hydroxyl ketone intermediate 5. Deprotection of the
hydroxyl groupswith hydrofluoric acid triggered
Me
Me
deprotection and subsequent spirocyclization to afford
O
O
H
9
H
the final spiroketal 4 asthe isngle product.
Thus, we
H
H
12
14
11
13
have succeeded in the stereocontrolled synthesis of the
key mother spiroketal C9–C23 portion of the HIV-1
protease inhibitive didemnaketals, in which the eight
stereocenters (10S,11S,12S,14S,16S,18R,20S, and 21S)
were constructed successfully. Further, study toward
total ysntheissof the didemnaketalsisongoing in our
group.
Me
H
9
S
S
OH
Me
18
Me
17
29
6. Still, W. C.; Barrish, J. C. J. Am. Chem. Soc. 1983, 105,
2487.
Zhao, Xue Zhi
