ENANTIOSELECTIVE SYNTHESIS OF MONOCERIN AND FUSARENTIN ETHERS: ANTIFUNGAL AND INSECTICIDAL FUNGAL METABOLITES.

Article abstract of DOI:10.1016/S0040-4039(00)60826-2

Fusarentin 4,5-dimethyl ether (4) is synthesized via condensation of the benzylic anion of ethyl 3,4,5-trimethoxy-6-methylbenzoate (7) with (S)-3-tetrahydropyranyloxyhexanal (8); subsequent biomimetic cyclisation of (4) gives monocerin (1).Keywords: Antif

Full text of DOI:10.1016/S0040-4039(00)60826-2

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Vol. 33. No. 49, pp.
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ENANTIOSELECTIVE SYNTHESIS OF MONOCERIN AND FUSARENTIN ETHERS:
ANTIFUNGAL AND INSECTICIDAL METABOLITES.
Michael P. Dillon, Thomas J. Simpson* and J.B. Sweeney
School of Chemistry, University of Bristol,
Cantock’s Close, Bristol,
Antifungal, insecticidal,
biomimetic, benxylic anion.
Abstract:
ether (4) is synthesized via
(7) with
cyclisation of (4) gives monocerin (I).
of
benzylic anion of eth yl
subsequent biomimetic
Monocerin
its
analogue (2) and the fusarentin ethers
have been isolated from
several
species and have been shown to exhibit antifungal, insecticidal and phytotoxic activity.
(3)
(4)
(5)
synthesis of fusarentin
The general strategy is based on condensation of the benzylic anion derived from ethyl
with a suitably protected as shown in Scheme 1.
ether (4) and its biomimetic cyclisation to
monocerht is now
The reuosynthetic analysis is based on the results of biosynthetic studies which were consistent with
of monocerin via the corresponding fusarentin ether (3) by oxidation to the quinone
This would allow tetrahydrofuran ring formation by conjugate addition of the 1
Scheme 2. The facile formation of (6) by oxidation of (3) or the reversible ring opening of (2) has been
responsible for the observed biological activities of thii group of
to C-8 as shown in
suggested to

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Scheme 1. Retrosynthetic analysis of monocerin
Scheme 2. Proposed interconversion of fusarentin methyl ether and monocerln
via a quinone
intermediate
The tetrahydropyranyl ether (8) of
in Scheme Brown has that
will convert aldehydes to homoallylic alcohols with high enantiomeric excess
and the benzoate were prepared as shown
derived from the readily available
Accordingly, treatment of butyraldehyde gave
converted to the tetrahydropyranyl ether
osmium tetroxide and sodium
Ethyl
in 76% yield (94%
and subsequent cleavage of the olefin using catalytic
gave the required
(7) was readily prepared by
followed by Dakin and methylation. Initial attempts to
in tetrahydrofuran gave no evidence
Changing the solvent from THF to pentane gave the ketone (1 the product of
This was
of ethyl
form the benzylic
using lithium
of anion formation.
self-condensation of the desired anion as the major product.
Formation of the anion in a sufficiently stable

7571
form for condensation with the aldehyde (8) was achieved by generation of LDA in pentane in the presence of
one equivalent of THF. Addition of a pentane solution of ethyl (7) at
gave a deep-red solution, characteristic of anion formation. The benzylic anion was
condensed with the aldehyde using a specially constructed
solution into the solution of the aldehyde at
which facilitated transfer of the anionic
LDA-THF,
TFA
TFA
NBS,
Scheme 3. Enantioselective synthesis of the fusarentin ethers and monocerin
After work-up the crude reaction mixture was deprotected to give the dihydroisocoumarin, formed by
spontaneous lactonisation of the initial aldol product, in 66% yield as a mixture of the desired
diastereoisomer (12) and its epimer (13). These diastereoisomers were separated by
multiple elution preparative The stereochemistry was by demethylation
of (13) to give

7572
fusarentin
ether (4.91%). The NMR spectrum and optical rotation of the
material
in
in agreement with those of the natural
=
=
Treatment
ether (4) under
direct cyclisation of the
showed an optical
1
onto the C-8 benzylic position to give monocerin (1) in 70% yield. This
of
NMR
=
compared to that of the isolated natural product ([a], =
High field
and
the presence of a single diastereoisomer.
Acknowledgements: We thank the SERC and Shell Research Ltd. for a studentship
and
Dr. J.
for his interest in
work.
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(Received in UK 22 June 1992)