ORGANIC
LETTERS
2008
Vol. 10, No. 24
5617-5619
Enantioselective Synthesis of a Simple
Benzenoid Analogue of Glycinoeclepin A
Simon Giroux and E. J. Corey*
Department of Chemistry and Chemical Biology, HarVard UniVersity, 12 Oxford
Street, Cambridge, Massachusetts 02138
Received October 24, 2008
ABSTRACT
A synthesis of the readily accessible glycinoeclepin A analogue 2 is reported.
Glycinoeclepin A (1), a biosynthetic product of the
soybean plant, diffuses from the plant roots into the soil
where, at concentration as low as 10-12 g/mL, it stimulates
hatching of eggs of the predatory nematode Heterodera
glycines.1 In the absence of a nearby growing plant, the eggs
of the nematode can remain unhatched and viable for many
months, emerging only when a plant becomes available. The
agricultural strategy of crop rotation is based on the disrup-
tion of this natural battle by spacing soybean crops over a
period of time larger than the survival time of the eggs of
H. glycines.
research to develop a biologically active mimic of glycino-
eclepin A that would be relatively simple to synthesize and
also sufficiently potent to be useful. Such a synthetic mimic
could be effective and practical even at levels of intrinsic
activity orders of magnitude below that of 1. Our initial
studies have focused on the tricyclic benzenoid analogue 2
of glycinoeclepin A. The selection of this analogue was
guided by the aim of trading off potency for synthetic
accessibility. Reported herein is a simple and potentially
practical synthesis of 2.
In principle, if the eggs of H. glycines could be induced
to hatch well in advance of the planting of new soybean
plants, destruction of the crop should be prevented, since
the lifetime of the hatched nematode itself is only a matter
of weeks. Thus, glycinoeclepin A (1) might be a useful
agrochemical. Unfortunately, 1 is produced only in trace
amounts by the soybean plant, and so naturally biosynthe-
sized glycinoeclepin A is essentially unavailable, even in
subgram amounts. Although glycinoeclepin A has been
obtained by total synthesis,2 the known synthetic processes
are too complex and costly to provide an unlimited and
inexpensive supply. We have, therefore, embarked on
Figure 1. Structure of glycinoeclepin A.
The synthesis of analogue 2 commenced with the con-
densation of 2-methylcyclopentanone and (R)-R-methylben-
zylamine and subsequent Michael reaction with tert-butyl
acrylate to provide the (S)-keto ester 3 (73% yield) after
acidic hydrolysis of the resulting imine.3 Conversion of 3 to
the corresponding vinyl triflate (NaHMDS, PhN(Tf)2, THF,
(1) (a) Fukuzawa, A.; Furusaki, A.; Ikura, M.; Masamune, T. J. Chem.
Soc., Chem. Commun. 1985, 221–222. (b) Masamune, T.; Anetai, M.;
Takasugi, M.; Katsui, N. Nature 1982, 297, 495–496.
10.1021/ol8024633 CCC: $40.75
Published on Web 11/13/2008
2008 American Chemical Society