Synthesis of danielone (α-hydroxyacetosyringone)

Article abstract of DOI:10.1039/a808061e

An efficient simple three step synthesis of the phytoalexin danielone (α-hydroxyacetosyringone) from acetosyringone is described.

Full text of DOI:10.1039/a808061e

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220 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 220^221y
Synthesis of Danielone (a-Hydroxyacetosyringone)y
Javier G. Luis* and Luc|a S. Andres
Instituto Universitario de Bio-organica ``Antonio Gonzalez'', Universidad de La Laguna,
Carretera de la Esperanza, 2. 38206 La Laguna, Tenerife, Canary Islands, Spain
An efficient simple three step synthesis of the phytoalexin danielone (a-hydroxyacetosyringone) from acetosyringone
is described.
a-Hydroxyacetosyringone (4), has recently been characterised
as a phytoalexin, named danielone,1 from Papaya (Carica
papaya). On the other hand, it has also been shown2 that
a-hydroxytacetosyringone plays an important role in the
specialized interaction between soil bacteria and plants,
speci¢cally activating Agrobacterium tumefaciens virulence
(Vir) gene expression.
a-Hydroxyacetosyringone (4) has not been synthesized until
now and we describe here an e¤cient, simple three step syn-
thesis of it from commercial acetosyringone (1).
ution to give, after acid treatment at re£ux, the deprotected
product (4) which was identical to the natural product
a-hydroxyacetosyringone.
Experimental
Preparation of Acetosyringone Potassium Salt 2.^A solution of
acetosyringone (1) (1.0 g, 5.1mmol) in methanol (30 ml) was added
to a solution of potassium hydroxide (4 equiv., 1.15 g, 0.2 mol) in
methanol (15 ml) and the mixture was stirred at room temp. for
1h. The mixture was cooled in an ice-bath and the solid formed
was ¢ltered o¡ on a Buchner funnel and rinsed with light petroleum
bp 30^40ꢁC). After removal of the light petroleum a white solid
remained which was dried well in a vacuum desiccator to give
dry acetosyringone potassium salt (1.2 g, quantitative yield).
Acetosyringone potassium salt 2. White solid, mp > 350 8C (Found:
a-Hydroxylation of ketones is commonly accomplished by
an indirect method, viz., by the addition of dioxygen
3
ꢀ O2† to an enolate3 with subsequent reduction of the
a-hydroperoxy ketone by triethyl phosphite.4 For example,
this is
dihydroxyacetone side-chain of a cortical steroid from a
17-acetyl precursor. Addition of 3O2 to organometallic
a
key reaction in the elaboration of the
1
C, 51.3; H, 4.8. C10H11O4K requires C, 51.26; H 4.73%); nmax/cm
C
(¢lm) 1622, 1509, 1458, 1374, 1297, 1213, 1184, 1117; lmax/nm (EtOH)
215, 301; dH (200 MHz, CD3OD) 2.47 (3H, s, CH3CO), 3.80 (6H,
enolates is inherently dangerous, and a serious explosion
‡
has been encountered in these laboratories.5 Direct
s, 2 Â Ar-OCH3) 7.22 (2H, s, 2 Â Ar-H); m/z 196 ꢀM K, 56%),
181(100), 153(7), 138(4), 108(3), 93(3) and 65(4).
hydroxylation of enolates is
a less common synthetic
Preparation of 30,50-Dimethoxy-40-methoxymethoxyacetophenone
3.^A mixture of 18-crown-6 (0.1 equiv., 136 mg, 0.5 mmol) and
acetosyringone potassium salt (350 mg, 1.5 mmol) in dry acetonitrile
(15 ml) was stirred at room temp. for 1h under nitrogen.
Chlorodimethyl ether (1.4 equiv., 0.16 ml, 2.1mmol) was added and
the mixture was stirred at room temp. for 2 h under nitrogen.
The mixture was cooled in an ice-bath, water added, and the
product extracted with ethyl acetate, washed with water and
brine and dried with anhydrous sodium sulfate. The crude reaction
product was puri¢ed by column chromatography using light
petroleum^ethyl acetate (1:1) as eluent to give 30,50-dimethoxy-
40 -methoxymethoxyacetophenone (3) (298.6 mg, 83%) as a white
transformation. Molybdenum peroxide pyridine-HMPA
(MoOPH) oxidation of the enolate yields the corresponding
acyloin but reaction with methyl ketones gives variable res-
ults.6
Application of the above methods on acetosyringone were
unsuccessful, giving complex mixtures. However, protection
of the p-hydroxyphenol group followed by application of
Moriarty's methodology7 for the a-hydroxylation of ketones
gave excellent results.
solid, mp 68^70 8C (Found: C, 60.0; H, 6.6. C12H16O5 requires C,
‡
1
O
1
O
59.99; H, 6.71%);
M
at m/z 240.100685 (calc. for C12H16O5,
(¢lm) 2966, 2938, 1678, 1585, 1456, 1414,
2′
240.099774); nmax/cm
OMe
OH
OMe
O–K+
1′
6′
3′
4′
1254, 1205, 1164, 1128, 1078, 950, 856; lmax/nm (EtOH) 218, 280;
dH (200 MHz, CDCl3) 2.58 (3H, s, CH3CO), 3.58 (3H, s, OCH3),
3.90 (6H, s, 2 Â Ar-OCH3), 5.19 (2H, s, OCH2O), 7.21 (2H, s,
2 Â Ar-H); dC (50 MHz, CDCl3) 26.28 (q, OCH3), 56.13 (q,
2 Â Ar-OCH3), 57.10 (q, C-2), 98.04 (t, OCH2O), 105.66 (d, C-20
and C-60), 132.80 (s, C-10), 139.05 (s, C-40), 153.10 (s, C-30 and C-50),
KOH/MeOH
r.t.
2
5′
OMe
OMe
1
2
ClCH2OMe
18-crown-6
MeCN
‡
196.71 (s, C-1); m/z 240 (M , 100%), 210(85), 195(50), 179(7), 181(7),
139(9), 137(8), 109(7), 66(6).
inert. atm.
Preparation of a-Hydroxyacetosyringone 4.^A solution of potassium
hydroxide (8 equivalents, 370 mg, 6.6 mmol) in methanol (10 ml) was
stirred at room temp. When the potassium hydroxide was dissolved
O
O
OMe
OH
OMe
i KOH/MeOH
the mixture was cooled in an ice-bath and
a solution of
30,50-dimethoxy-40 -methoxymethoxyacetophenone (198 mg, 0.8 mmol)
in methanol (10 ml) was added slowly. Then iodobenzene diacetate
(1.5 equiv., 398.6 mg, 1.24 mol) was added in small portions and
the reaction mixture stirred at room temperature overnight, then
cooled in an ice-bath and a solution of hydrochloric acid 6% added
until the reaction mixture was acidic by pH indicator. After re£uxing
at 60 8C for 1h the reaction mixture was cooled at room temp. and
water added. The product was extracted with ethyl acetate, the
organic layers washed with water and brine and dried over anhydrous
sodium sulfate. The crude product was chromatographed on silica gel
in a small plug with light petroleum^ethyl acetate (1:1) as eluent to
ii Phl(OAc)2
0 ˚C to r.t.
iii H +, reflux
OH
OCH2OMe
OMe
OMe
4
3
Scheme 1
Acetosyringone (1) was protected using chlorodimethyl
ether to give (3) (Scheme 1). Compound 3 reacted with
iodobenzene diacetate in methanol^potassium hydroxide sol-
‡
give (4) as a yellow solid (130 mg, 60%); M at m/z 212.067631 (calc.
1
for C10H12O5, 212.068474); nmax/cm (¢lm) 3495, 3239, 1675, 1614,
1587, 1519, 1455, 1325, 1216, 1096, 847. The remainder of the
spectroscopic data were identical to those given in the literature
for the natural product.
This work has been subsidized by Grant PI1998/006 from
the Gobierno Autonomo de Canarias.
* To receive any correspondence.
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1999 221
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WARNING: Stirring of a solution of butyrolactone and LDA
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E. Vedejs, D. A. Vazquez and D. R. Pelegrina, Tetrahedron
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R. M. Moriarty, H. Hu and S. C. Gupta, Tetrahedron Lett.,
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Received, 19th October 1998; Accepted 9th December 1998
Paper E/8/08061E
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