Next Article in Journal
Hydroxyquinones: Synthesis and Reactivity
Previous Article in Journal
Synthesis of Some Fused Pyrazoles and Isoxazoles
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Synthesis of α-Hydroxyacetosyringone

Department of Chemistry, Universidad de Antioquia, P. O. Box 1226. Medellín, Colombia
*
Author to whom correspondence should be addressed.
Molecules 2000, 5(12), 1287-1290; https://doi.org/10.3390/51201287
Submission received: 25 May 2000 / Accepted: 1 November 2000 / Published: 19 December 2000

Abstract

:
A phytoalexin from papaya fruit has been synthesized in four steps; this procedure involved a Pummerer- type reaction.

Introduction

From papaya slices treated with copper salt or infected with Collectotrichum gloesporioides we isolated α-hydroxyacetosyringone as a phytoalexin [1,2]; recently, this compound was involved in plant-pathogen interactions, e.g. it is the major virulence gene activating factor and promotes high efficiency transformation of Arabidopsis thaliana explants by Agrobacterium tumefaciens [3,4].
Although its synthesis has been reported previously [5], we report here a four-steps synthesis of this compound

Results and Discussion

We attempted to synthesize α-hydroxyacetosyringone through a sequence of reactions including a Pummerer reaction. According to Russell and Becker [6,7], aromatic β-ketosulphoxides can be used to extend the carbon chain and also to add the desired new functional group. These β-ketosulphoxides are produced by reaction between DMSO and aldehydes or ketones in basic solutions and oxidation of the respective β-hydroxysulfoxide intermediate with MnO2 .
However, β-hydroxysulfoxides can yielded α,β-unsaturated sulfoxides under acidic conditions or upon neutralization of the condensation reaction. Moreover, other unexpected compounds have been isolated too, and their formation involved addition of water to α,β-unsaturated sulfoxide in an acid-catalyzed process [8]. Surprisingly, α-hydroxyacetosyringone was directly produced, via attack of two water molecules and thiomethanol elimination in a pH-dependent sequence of reactions.
Thus, when this coupling reaction was carried out between 4-O-benzyl-syringaldehyde and DMSO product 2 was obtained. This product can be transformed into 3 through a Pummerer-type reaction (Scheme 1); treatment of this substance with concentrated hydrochloric acid during 5 hours yielded a mixture of compounds, including compound 3. After hydrogenation of 3 on Pd/C the desired product 4 was obtained (<10% yield from 2). Its spectroscopic data were identical to those α-hydroxy acetosyringone obtained from natural sources.

Experimental

General

NMR spectra were recorded with a Bruker AMX III (at 300 MHz for 1H and 75.0 MHz for 13C). All NMR spectra were taken in CDCl3; MS on a VG Micromass ZAB-2F at 70 eV; IR spectra were registered with a Perkin Elmer 1600 (FTIR).. TLC and column chromatographies were run using Merck silica gel and, unless otherwise specified, developed with n-hexane-ethyl acetate (9:1, v/v)

4-Benzyloxysyringaldehyde (1)

The commercial compound 3,5-dimethoxy-4-hydroxy-benzaldehyde (syringaldehyde) (91.09 mg, 0.5 mmol) in MeOH (5 mL) was treated with benzyl chloride (0.12 mL, 1.0 mmol) and stirred for 8hours at room temperature. Compound 1 was purified by silica gel column. HRMS: 272.1049. 1H NMR: 3.91 (6H, s, x 2-OCH3), 5.14 (2H, s, ArCH2O-), 7.12 (2H, s, H-3, H-5), 7.35 (3H, m, Ar), 7.47 (2H, d, J=6.1, Ar), 9.78 (1H, s, CHO). 13C NMR: 53.89 (q, - OCH3), 75.69 (t, -O-CH2), 107.31 (d, C-3, C-5), 129.08 (s, C-1), 143.01 (s, C-2,C-6), 154.63 (s, C-4), 191.83 (s, CHO).

3’,5’-Dimethoxy-4’-benzyloxyethenylmethylsulfoxide (2)

A solution of t-BuOK (179.55 mg, 1.6 mmol) in DMSO (5.0 mL) was added to 4-O-benzyl-syringaldehyde (272.30 mg, 1.0 mmol) 1, in DMSO (3.0 mL) under argon and stirred overnight. After extraction with ethyl acetate and purification by column chromatography, compound 2 was obtained (199.45 mg, 60%). TLC: Rf = 0.35; mp 102-104 oC. HRMS: 332.1082. 1H NMR 300 MHz (δ ppm CDCl3) 2.70 (3H, s, S–CH3), 3.83 (6H, s, –OMe), 5.02 (2H, s, ArCH2O-), 6.67 (2H, s, H-2’ and H-6’), 6.80 (1H, d, 14.0 Hz, =CH–S), 7.14 (1H, d, 14.0 Hz, Ar–CH=), 7.28-7.36 (3H, m, Ar), 7.46 (2H, dd, 2.0 and 7.0 Hz, Ar); 13C NMR 75.46 MHz: 41.01 (q, S-CH3), 56.10 (q, O-CH3), 75.06 (t, -ArCH2O-), 104.70 (d, C-2, C-5), 129.14 (d, -S-C=CH), 128.15 (d, Bz), 128.44 (s, C-1), 136.51 (d, S-CH=C), 137.41 (s, C-1’), 138.31 (s, C-4), 153.71 (s, C-3, C-5).

4’-O-benzyl-α-hydroxyacetosyringone (3)

The sulfoxide 2 (166.21 mg, 0.5 mmol) was added to 10% HCl (10 mL) and heated to reflux for five hours. The crude reaction mixture was purified by TLC (silicagel; n-hexane-ethyl acetate 6:1, v/v) and product 3 was thus obtained as a yellow oil (15.11 mg, 10%). HRMS: 302.1154. 1H NMR : 3.68 (6H, s, x 2 OCH3), 5.07 (2H, s, -COCH2OH), 5.08 (2H, s, Ar-OCH2-), 6.48 (1H, s, -OH), 6.90 (2H, s, H-2’ and H-6’), 7.30 (5H, m, benzyl); 13C NMR: 56.49 (q, x 2 OCH3), 75.39 (t, x 2CH2), 107.40 (d, C-2’ and C-5’ ), 128.80 (d, Bz), 132. 90 (s, C-1’), 134.80 (s, C-1’’), 138.87 (s, C-4’), 153.45 (s, C-3’, C-5’), 192.15 (s, CO).

α-Hydroxyacetosyringone (4)

Compound 3 (15.11 mg, 0.05 mmol) in MeOH (5 mL) was hydrogenated at room temperature for 5 hours over Pd/C and after workup compound 4 was recovered (10 mg, yield 95%). Its spectroscopical and physical properties were compared to an authentic sample obtained from papaya slices. mp. 145 º, Rf = 0.28 (n-hexane-ethyl acetate 2:3). HRMS: 212.0685. 1H NMR : 3.25 (H, s, 2-OH), 3.89 (6H, s, 3’,5’-OCH3), 4.93 (2 H, d, J=1.9, -COCH2OH), 6.34 (H, t, J=1.9, 4-OH), 7.28 (2H, s. H-2’ and H-6); 13C NMR: 54.95 (q, x 2 OCH3), 66.3 (t, C-2), 106.2 (d, C-2), 125.1 (s, C-1), 141.3 (s, C-4), 146.6(s, C-3, C-5), 196.4 (s, C-1).

Acknowledgments

Author thanks to COLCIENCIAS (Colombia) and Universidad de Antioquia for financial support.

References

  1. Echeverri, F.; Torres, F.; Quiñones, W.; Cardona, G.; Archbold, R.; Roldán, J.; Gutierrez, J.; Hassane, E. L. Phytochemistry 1996, 44, 255–256.
  2. Echeverri, F.; Torres, F.; Quiñones, W.; Cardona, G.; Archbold, R.; Roldán, J.; Brito, I.; Gutierrez, J.; Lahlou, E-H. “Memorias III Simposio Internacional de Química de Productos Naturales y sus Aplicaciones”; Sociedad Chilena de Química-U. de Chile, Santiago y Catolica de Chile: Punta de Tralca (Chile), 1996 December 4-7; pp. 125–126. [Google Scholar]
  3. Song, Y. N.; Shibuya, M.; Ebizuka, Y.; Sankawa, U. Chem. Pharm. Bull. 1990, 38, 2063–2065.
  4. Sheikholeslam, S. N.; Weeks, D.B. Plant Mol. Biol. 1987, 8, 291–298. [PubMed]
  5. Luis, J. G.; San Andres, L. J. Chem. Res. (S) 1999, 220–221. [CrossRef]
  6. Russell, G. A.; Becker, H. D. J. Am. Chem. Soc. 1963, 85, 3406–10.
  7. Becker, H. D.; Mikol, G.; Russell, G. J. Am. Chem. Soc. 1963, 85, 3410–3414.
  8. Russell, G.; Mikol, G. J. Am. Chem. Soc. 1966, 88, 5498–5504.
  • Sample Availability: Samples are available from the authors.
Scheme 1. Reactions involved in acetosyringone synthesis.
Scheme 1. Reactions involved in acetosyringone synthesis.
Molecules 05 01287 sch001

Share and Cite

MDPI and ACS Style

Echeverri, F.; Quiñones, W.; Torres, F.; Duque, M.; Archbold, R. Synthesis of α-Hydroxyacetosyringone. Molecules 2000, 5, 1287-1290. https://doi.org/10.3390/51201287

AMA Style

Echeverri F, Quiñones W, Torres F, Duque M, Archbold R. Synthesis of α-Hydroxyacetosyringone. Molecules. 2000; 5(12):1287-1290. https://doi.org/10.3390/51201287

Chicago/Turabian Style

Echeverri, Fernando, Winston Quiñones, Fernando Torres, Mario Duque, and Rosendo Archbold. 2000. "Synthesis of α-Hydroxyacetosyringone" Molecules 5, no. 12: 1287-1290. https://doi.org/10.3390/51201287

Article Metrics

Back to TopTop