Scheme 1. Synthesis of Ketone 5
Figure 1. Retrosynthetic analysis of (-)-platensimycin.
As shown in Scheme 1, commercially available (+)-
carvone 6 was transformed to the known lactone 5 by slight
modification of a literature procedure.7 Our initial Baeyer-
Villiger oxidation of lactone 5 with mCPBA proceeded very
slowly and the corresponding oxidation product was obtained
in poor yield (20%). However, lactone 5 was successfully
transformed into the corresponding ester in 89% yield by
using trifluoroperoxyacetic acid formed in situ from trifluo-
roacetic anhydride and the urea hydrogen peroxide complex
(UHP) at 0 °C for 5 h.8 Saponification of the resulting ester
furnished alcohol 7 in 90% yield. Protection of the alcohol
7 with TBSCl gave the silyl ether in quantitative yield. The
lactone was subjected to the Petasis olefination9 with Cp2-
TiMe2 in toluene at 90 °C to provide the corresponding enol
ether. Hydroboration of the resulting enol ether with 9-BBN
provided the desired primary alcohol 8 and its diastereomer
9 as a 2:1 mixture of diastereomers in 81% yield.10 The
diastereomers were separated by flash chromatography. The
major diastereomeric alcohol 8 was protected as the TBDPS
group to provide the corresponding bis-silyl ether in 98%
yield. Selective cleavage of the secondary TBS ether with a
catalytic amount of DDQ in 9:1 THF and water afforded
the secondary alcohol in 93% yield.11 Swern oxidation of
this alcohol provided ketone 10 in 96% yield.
Nicolaou and co-workers. They reported the synthesis of its
analogue adamantaplatensimycin recently.4c Two other ra-
cemic syntheses5a,b and a related structure of the oxatetra-
cyclic core have also been reported.5c The above-mentioned
syntheses utilized an intramolecular etherification reaction
to construct the hydrophobic core of platensimycin. Very
recently, Yamamoto and co-workers reported an elegant
enantioselective route to (-)-platensimycin using an in-
tramolecular Robinson annulation as the key step.6 This
report has prompted us to publish our preliminary results
toward the total synthesis of (-)-platensimycin.
Our strategy, however, is based upon an intramolecular
Diels-Alder reaction of an appropriately functionalized
substrate to construct the oxatetracyclic core in a stereocon-
trolled manner. As shown in Figure 1, the oxatetracyclic core
2 can be formed by an intramolecular Diels-Alder reaction
of substrate 3. For preliminary investigation, we planned to
examine a Diels-Alder reaction with the mixture of E/Z
isomers as shown in 3. In principle, both expected products
can be converted to the oxatetracyclic core enone derivative.
Diels-Alder substrate 3 can be synthesized from ketone 4
by constructing the diene and dienophile moiety at each side
of the bicyclic ketone 4. Ketone 4 can be derived from the
lactone 5 by olefination of the lactone carbonyl followed by
hydroboration of the resulting olefin to set up the required
stereocenter. Lactone 5 will be synthesized starting from
commercially available (+)-carvone 6.
The synthesis of substrate 3 is outlined in Scheme 2.
Installation of diene from ketone 10, required an olefin
(7) (a) Srikrishna, A.; Hemamalini, P. J. Org. Chem. 1990, 55, 4883.
(b) Weinges, K.; Reichert, H. Synlett 1991, 785. (c) Weinges, K.; Reichert,
H.; Huber-Patz, U.; Irngartinger, H. Liebigs Ann. Chem. 1993, 403. (d)
Weinges, K.; Reichert, H.; Braun, R. Chem. Ber. 1994, 127, 549.
(8) Copper, M. S.; Heaney, H.; Newbold, A. J.; Sanderson, W. R. Synlett
1990, 533.
(9) (a) Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc. 1990, 112, 6392.
(b) Dollinger, L. M.; Ndakala, A. J.; Hasshemzadeh, M.; Wang, G.; Wang,
Y.; Martinez, I.; Arcari, J. T.; Galluzzo, D. J.; Howell, A. R. J. Org. Chem.
1999, 64, 7074.
(4) (a) Nicolaou, K. C.; Li, A.; Edmonds, D. J. Angew. Chem., Int. Ed.
2006, 45, 7086. (b) Nicolaou, K. C.; Li, A.; Edmonds, D. J.; Tria, G. S.
Angew. Chem., Int. Ed. 2007, 46, 3942. (c) Nicolaou, K. C.; Lister, T.;
Denton, R. M.; Montero, A.; Edmonds, D. J. Angew. Chem., Int. Ed. 2007,
46, 4712.
(5) (a) Zou, Y.; Chen, C.-H.; Taylor, C. D.; Foxman, B. M.; Snider, B.
B. Org. Lett. 2007, 9, 1825. (b) Nicolaou, K. C.; Tang, Y.; Wang, J. Chem.
Commun. 2007, 1922. (c) Kaliappan, K. P.; Ravikumar, V. Org. Lett. 2007,
9, 2417.
(10) Lambert, W. M.; Hanson, G. H.; Benayoud, F.; Burke, S. D. J.
Org. Chem. 2005, 70, 9382.
(6) Li, P.; Payette, J. N.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129,
9534.
(11) (a) Crouch, R. D. Tetrahedron 2004, 60, 5833. (b) Tanemura, K.;
Suzuki, T.; Horaguchi, T. J. Chem. Soc., Perkin Trans. 1 1992, 2997.
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