A chemoenzymatic synthesis of the styryllactone (+)-goniodiol from naphthalene

Article abstract of DOI:10.1039/b205230j

The enantiomerically pure cis-1,2-diol 2, which is obtained by microbial oxidation of naphthalene, has been converted, via a sequence of reactions including oxidative C-C bond cleavage, decarbonylation and ring-closing metathesis steps, into the natural p

Full text of DOI:10.1039/b205230j

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A chemoenzymatic synthesis of the styryllactone (؉)-goniodiol
from naphthalene
Martin G. Banwell,* Mark J. Coster, Ochitha P. Karunaratne and Jason A. Smith
1
Research School of Chemistry, Institute of Advanced Studies,
The Australian National University, Canberra, ACT 0200, Australia.
E-mail: mgb@rsc.anu.edu.au
Received (in Cambridge, UK) 29th May 2002, Accepted 12th June 2002
First published as an Advance Article on the web 25th June 2002
The enantiomerically pure cis-1,2-diol 2, which is obtained
by microbial oxidation of naphthalene, has been
converted, via a sequence of reactions including oxidative
C–C bond cleavage, decarbonylation and ring-closing
metathesis steps, into the natural product (؉)-goniodiol
(1).
to acetonide group migration it was immediately acetylated
thus affording the stable product 6 {53% from 4, [α]D = Ϫ236 ×
10Ϫ1 deg cm2 gϪ1 (c 5.7)}. Decarbonylation of compound 6,
so as to generate compound 7 and thereby excise the single
superfluous carbon associated with the starting material 2,
could be effected with Wilkinson’s catalyst [RhCl(PPh3)3] in
refluxing xylene.12 However, stoichiometric quantities of this
“catalyst” were required because the resulting carbonyl–metal
complex is stable and does not, therefore, “turn over” (addition
of diphenyl phosphorazidate proved ineffective13). To circum-
vent such difficulties, bis[1,3-bis(diphenylphosphino)propane]-
(ϩ)-Goniodiol (1) was first isolated from the leaves and twigs of
the Asian tree Goniothalamus sesquipedalis,1 and is a represent-
ative member of the styryllactone class of natural product,
many of which show potent and selective cytotoxic properties.2
For example, the title compound exhibits significant toxicity
against the human lung carcinoma cell line A-549 (ED50
0.122 µg mLϪ1) whilst showing no such effects in a brine
shrimp assay (LC50 > 500 µg mLϪ1). As a consequence, various
groups have developed useful synthetic approaches to the
styryllactones with a particular emphasis having been placed on
goniodiol (1), partly because a variety of its natural congeners
are readily derived from this source. Two basic strategies have
emerged. The first employs the chiron approach, as reported
by Honda and co-workers3 [using 2,3-O-isopropylidene--
glyceraldehyde], Surivet and Vatéle4 [using (R)-(Ϫ)-mandelic
acid†] and Ley and co-workers5 [using S-(Ϫ)-glycidol†]. The
second exploits stoichiometric and catalytic asymmetric
induction methodologies as described by Vatéle and co-
workers6 (chiral auxiliary-mediated nucleophilic addition
to benzaldehyde), Mukai and co-workers7 (chiral auxiliary-
mediated nucleophilic addition to benzaldehyde) and Yang
and Zhou8 (Sharpless asymmetric epoxidation of cinnamyl
alcohol). Herein we report a third approach to (ϩ)-goniodiol
(1), namely a chemoenzymatic synthesis which employs the
enantiopure 1,2-dihydronaphthalene diol 29 as a starting
material. Although compound 2 is available in kilogram
quantities via microbial dihydroxylation of naphthalene, the
present work provides the first example of its exploitation in
natural product synthesis.
rhodium tetrafluoroborate [Rh(dppp)2ϩBF4Ϫ],14
a species
known to effect decarbonylation of aromatic aldehydes, was
used instead and the target 7 (76% at 64% conversion) was
thereby obtained using only 10 mol% of the metal complex.
Hydrolysis of acetate 7 with potassium carbonate in methanol
afforded the corresponding alcohol 8 {93%, [α]D = Ϫ84 × 10Ϫ1
deg cm2 gϪ1(c 3.7, MeOH)} which was oxidized to the unstable
aldehyde 9 using TPAP–NMO.
Allylation of compound 9, as required for introduction of
one of the two terminal double bonds that would participate
in a ring-closing metathesis (RCM) so as to form the α,β-
unsaturated lactone ring of target 1, proved difficult to perform
with the appropriate levels of stereocontrol. Of the various
reagents and conditions examined15–19 the most effective proved
to be those involving allyltributylstannane in the presence
of lithium perchlorate16 and it is presumed this reaction is pro-
ceeding under conditions of chelation control.20 Whilst the
resulting ca. 2.7 : 1 mixture of compounds 10 {[α]D = Ϫ56 ×
10Ϫ1 deg cm2 gϪ1 (c 0.5)} and 11 {[α]D = Ϫ32 × 10Ϫ1 deg cm2 gϪ1
(c 1.4)} (70% combined yield from 8)¶ could be separated by
HPLC, for preparative purposes it was more convenient to
immediately subject this mixture to acylation with acrylic
anhydride in the presence of DMAP. In this manner the
corresponding mixture of acrylates 12 {mp = 36–38 ЊC,
[α]D = Ϫ11 × 10Ϫ1 deg cm2 gϪ1 (c 0.6)} and 13 {mp = 42–43 ЊC,
[α]D = Ϫ95 × 10Ϫ1 deg cm2 gϪ1 (c 1.1)} (ca. 50% combined yield)
was obtained. In keeping with the behaviour21 of many other
acrylates derived from homoallylic alcohols, these compounds
readily participated in
a ring-closing metathesis (RCM)
reaction when treated with 10 mol% of (Cy P) Cl Ru᎐CHPh
᎐
3
2
2
(Grubbs’ “first generation” catalyst)22 in dichloromethane at
ambient temperatures. The ensuing pyranones 14 {79%, mp =
137–138 ЊC, lit.8 mp = 133–134 ЊC, [α]D = Ϫ95 × 10Ϫ1 deg cm2
gϪ1 (c 0.5, EtOH), lit.8 [α]D = Ϫ100 × 10Ϫ1 deg cm2 gϪ1 (c 0.9,
EtOH)} and 15 {73%, mp = 97–98 ЊC, [α]D = Ϫ27 × 10Ϫ1 deg
cm2 gϪ1 (c 0.4)} were readily separated by flash chromatography
on silica gel. The spectroscopic data obtained on the former
product matched those derived from authentic material.5,8
Deprotection of compound 14 with aqueous acetic acid at
80 ЊC5 finally afforded (ϩ)-goniodiol (1) {98%, [α]D = ϩ72 ×
10Ϫ1 deg cm2 gϪ1 (c 0.3), lit.2 [α]D = ϩ74.4 × 10Ϫ1 deg cm2 gϪ1
The reaction sequence begins (Scheme 1) with the conversion,
under standard conditions, of diol 2 into the corresponding and
previously reported10 acetonide 3 (99%). Oxidative cleavage of
the double bond associated with the latter was achieved
using OsO4–NaIO4 and the resulting unstable dialdehyde was
immediately reduced to the diol 4‡ {46% from 3, [α]D = Ϫ80 ×
10Ϫ1 deg cm2 gϪ1 (c 3.0)§} using NaBH4 in methanol. The
benzylic alcohol moiety within compound 4 was selectively
oxidized using manganese dioxide11 so as to give the benzalde-
hyde 5 (73%). Since this latter compound was especially prone
1
(c 0.3, CDCl3)} the H and 13C NMR spectral data for which
matched those reported previously.2,5 Analogous deprotection
of compound 15 gave 6-epi-(ϩ)-goniodiol 16 {85%, [α]D = Ϫ47
× 10Ϫ1 deg cm2 gϪ1 (c 0.3)}.
1622
J. Chem. Soc., Perkin Trans. 1, 2002, 1622–1624
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b205230j

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Scheme 1 Reagents and conditions: (i) 2,2-DMP, p-TsOH (cat.), 18 ЊC, 1.5 h; (ii) (a) OsO4 (10 mol%), 3 : 1 v/v DME–H2O, 18 ЊC, 0.25 h then NaIO4
(3 mol equiv.), 18 ЊC, 15 h; (b) NaBH4 (4 mol equiv.), MeOH, 0 ЊC, 2 h; (iii) MnO2 (20 mol equiv.), DME, 18 ЊC, 3 h; (iv) Ac2O (6 mol equiv.), DMAP
(cat.), pyridine (6 mol equiv.), DCM, 18 ЊC, 2 h; (v) [Rh(dppp)2]ϩBF4Ϫ (10 mol%), xylene, ca. 140 ЊC, 15 h; (vi) K2CO3 (10 mol equiv.), MeOH, 18 ЊC,
0.25 h; (vii) NMO (1.7 mol equiv.), TPAP (17 mol%), powdered 4 Å molecular sieves, DCM, 18 ЊC, 0.66 h; (viii) H2C᎐CHCH2SnBu3 (3 mol equiv.),
᎐
LiClO4 (5 M in Et2O), 18 ЊC, 4 h; (ix) acrylic anhydride (20 mol equiv.), DMAP (40 mol equiv.), THF, Ϫ20 to 18 ЊC, 16 h; (x) (Cy3P)2Cl2Ru᎐CHPh (10
᎐
mol%), DCM, 18 ЊC, 4 h then DMSO (10 mol equiv.), 18 ЊC, 16 h; (xi) 1 : 1 v/v AcOH–H2O, 80 ЊC, 0.5 h.
250.1205, 0.4%), 235 (25), 192 (19), 148 (100), 133 (82), 119
(61), 101 (78), 91 (68).
Experimental
Compound 7
Degassed xylene (1 mL) was added to a mixture of aldehyde
Acknowledgements
6 (165 mg, 590 µmol) and bis[1,3-bis(diphenylphosphino)-
propane]rhodium tetrafluoroborate (63 mg, 10 mol%) main-
tained under an atmosphere of nitrogen. The ensuing mixture
was stirred magnetically whilst being heated at reflux for 15 h.
The cooled reaction mixture was filtered through a pad of
Celite which was washed with ether (5 mL). The combined
filtrates were concentrated under reduced pressure and the
resulting brown oil subjected to flash chromatography (silica,
1 : 4 ethyl acetate–hexane elution) and thereby yielding two
fractions, A and B.
Dr Gregg Whited is warmly thanked for providing generous
quantities of the diol 2. We thank the Institute of Advanced
Studies (IAS) and the Australian Research Council for financial
support. Professors S. V. Ley and W.-S. Zhou are thanked
for providing spectral data derived from synthetic samples of
compounds 1 and 14. Technical assistance from Dr Eric
Wenger (IAS), Dr Carl Braybrook (CSIRO Molecular
Science, Melbourne) and Mr Lee Welling (IAS) is gratefully
acknowledged.
Concentration of fraction A (Rf 0.25) gave the starting
aldehyde 6 (59 mg, 36% recovery) which was identical, in all
respects, with an authentic sample.
Notes and references
Concentration of fraction B (Rf 0.40) gave the title compound
7 (71.4 mg, 76% yield at 64% conversion) as a white crystalline
solid, mp = 65–68 ЊC, [α]D Ϫ109 × 10Ϫ1 deg cm2 gϪ1 (c 1.1)
(Found: C, 67.1; H, 7.2. C14H18O4 requires C, 67.2; H, 7.3%).
νmax (KBr)/cmϪ1 1735, 1376, 1237, 1212, 1087, 1033, 983, 752
and 704; δH (300 MHz, CDCl3) 7.38–7.30 (5H, complex m),
5.32 (1H, d, J 6.9 Hz), 4.56 (1H, ddd, J 8.0, 6.9 and 4.4 Hz),
3.71 (1H, dd, J 11.7 and 4.4 Hz), 3.61 (1H, dd, J 11.7 and
8.0 Hz), 1.92 (3H, s), 1.65 (3H, s), 1.49 (3H, s); δC (75 MHz,
CDCl3) 170.8, 136.3, 128.7, 128.5, 126.7, 109.5, 78.7, 76.5, 64.5,
† The IUPAC name for mandelic acid is phenylglycolic acid. The
IUPAC name for glycidol is 2,3-epoxypropan-1-ol.
‡ All new and stable compounds had spectroscopic data [IR, NMR,
mass spectra] consistent with the assigned structure. Satisfactory com-
bustion and/or high-resolution mass spectral analytical data were
obtained for new compounds and/or suitable derivatives.
§ All optical rotations were determined in a chloroform solution at
20 ЊC unless otherwise specified.
¶ The assignment of stereochemistry at C-6 (goniodiol numbering) in
products 10 and 11 follows from their conversions into 6-epi-(ϩ)-
goniodiol (16) and (ϩ)-goniodiol (1), respectively.
27.6, 25.2, 20.9; m/z (EI) 250.1205 (Mϩ , C14H18O4 requires
ؒ
J. Chem. Soc., Perkin Trans. 1, 2002, 1622–1624
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