Synthesis of α-Hydroxyacetosyringone

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 MnO 2 .Scheme 1.Reactions involved in acetosyringone synthesis.
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 acidcatalyzed 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.

General
NMR spectra were recorded with a Bruker AMX III (at 300 MHz for 1 H and 75.0 MHz for 13 C).All NMR spectra were taken in CDCl 3 ; 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)