ORGANIC
LETTERS
2011
Vol. 13, No. 12
3206–3209
Formal Synthesis of Leustroducsin B via
Reformatsky/Claisen Condensation of
Silyl Glyoxylates
Stephen N. Greszler, Justin T. Malinowski, and Jeffrey S. Johnson*
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill,
North Carolina 27599-3290, United States
Received April 27, 2011
ABSTRACT
A formal synthesis of leustroducsin B has been completed. The synthesis relies upon a recently developed Reformatsky/Claisen conden-
sation of silyl glyoxylates and enantioenriched β-lactones that establishes two of the molecule’s three core stereocenters and permits fur-
ther elaboration to an intermediate in Imanishi’s synthesis via reliable chemistry (Prasad reduction, asymmetric pentenylation, Mitsunobu
inversion).
The leustroducsin1 and phoslactomycin2 families of
natural products were first isolated in 1993 by Kohama
et al. from the culture broth of Streptomyces platensis
and were later found to exhibit interesting antifungal,
antibacterial, and antitumor activities.1b,2b,3a,3b These
natural products boast intriguing molecular architec-
tures: common features include a highly congested
and functionalized core flanked by dihydropyr-
one and cyclohexyl moieties and a central tertiary
alcohol with vicinal phosphate and aminoethyl
substituents.
The individual members of this natural product fa-
mily are largely distinguished by the substituent present
at C18 of the cyclohexyl ring (Figure 1), a structural
feature which has been shown to partially modulate a
variety of biological activities attributed to the leustro-
ducsins and phoslactomycins.1a,2a Particularly notable
is leustroducsin B (C18: 6-methyloctanoate), which has
(1) (a) Kohama, T.; Enokita, R.; Okazaki, T.; Miyaoka, H.;
Torikata, A.; Inukai, M.; Kaneko, I.; Kagasaki, T.; Sakaida, Y.; Satoh,
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T.; Kinoshita, T.; Kaneko, I.; Shiraishi, A. J. Antibiot. 1993, 46, 1512. (c)
Matsuhashi, H.; Shimada, K. Tetrahedron 2002, 58, 5619.
(4) Shimada, K.; Kaburagi, Y.; Fukuyama, T. J. Am. Chem. Soc.
2003, 125, 4048.
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42, 1019. (b) Fushimi, S.; Furihata, K.; Seto, H. J. Antibiot. 1989,42, 1026. (c)
Ozasa, T.; Suzuki, K.; Sasamata, M.; Tanaka, K.; Koburi, M.; Kadota, S.;
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Matsumoto, H.; Iwanami, M. J. Antibiot. 1989, 42, 1339. (e) Shibata, T.;
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(3) (a) Lewy, D. S.; Gauss, C. M.; Soenen, D. R.; Boger, D. L. Curr.
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(5) (a)Miyashita, K.;Tsunemi, T.;Hosokawa, T.;Ikejiri, M.;Imanishi,
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(6) Moise, J.; Sonowane, R. P.; Corsi, C.; Wendeborn, S. V.;
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(7) For phoslactomycin B syntheses, see: (a) Wang, Y.-G.; Takeyama
T.; Kobayashi, Y. Angew. Chem., Int. Ed. 2006, 45, 3320. (b) Nonaka,
H.; Maeda, N.; Kobayashi, Y. Tetrahedron Lett. 2007, 48, 5601.
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€
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r
10.1021/ol2011192
Published on Web 05/17/2011
2011 American Chemical Society