Syringaldehyde

Overview

Syringaldehyde is a promising aromatic aldehyde that no longer deserves to remain in obscurity. It possesses worthy bioactive properties and is, therefore, used in pharmaceuticals, food, cosmetics, textiles, pulp and paper industries, and even in biological control applications. Mostly, the synthetic form of syringaldehyde is being used. The ever-increasing safety concerns over synthetic antioxidants and the harmful side effects of chemo-therapeutic drugs, coupled with their high costs^[1], have created a new path for the development of cheaper, sustainable, and most crucially, natural anti-oxidants, drugs, and food additives^[2]. Syringaldehyde, a compound found only in a minute quantity in nature, is believed to be a promising source that matches the abovementioned requisites.
Syringaldehyde, or 3,5-dimethoxy-4-hydroxybenzaldehyde, is a naturally occurring unique compound with assorted bioactive characteristics that belongs to the phenolic aldehyde family. Syringaldehyde is very similar in structure to its infamous counterpart, vanillin, and it has comparable applications^[3]. Though not as well commercialized as vanillin, syringaldehyde chemistry and its manipulation are emerging rather rapidly, especially after the discovery of its role as an essential intermediate of the antibacterial drugs Trimethoprim, Bactrim, and Biseptol^[4]. Bactrim or Biseptol are combinations of Trimethoprim with sulfamethoxazole. These drugs are common bactericides.

Figure the chemical structure of syringaldehyde

Natural sources

An excellent natural source of syringaldehyde lies within the cell walls of plants. Being the second most copious biopolymer only to cellulose, lignin offers a continuous, renewable, and cheap supply of syringaldehyde. This is promising, since lignin is discarded as waste by the pulping industry and is also a major by-product from the biomass-to-ethanol conversion process^[5]. Despite the fact that the fate of lignin ends at a bio-fuel refinery^[6], its hidden wealth can be extracted prior to its conversion into biomass feedstock. Although this practice is not common for the recovery of syringaldehyde, it is slowly emerging, since value-added products from wastes offer a promising future.
Years of tedious research have led to the current development and understanding of the synthesis of the syringyl unit in plants. Lignin being an amorphous heteropolymer, the elucidation of its biosynthetic pathway is not an easy task. In order to appreciate the complexity and diversity of nature and her unique attributes, it is vital to know how the syringyl unit comes into existence in lignin. Moreover, the bio-origin of this compound has not been adequately reviewed. Protolignin (naturally occurring lignin) varies in molecular make-up from plant to plant and even from cell to cell^[7]. Research demonstrated that Arabidopsis mutants were no longer upright since they lacked lignified interfascicular fibers, providing evidence that macro-metabolite lignin is responsible for the structural integrity of plants. Lignin also provides plants with a vascular system for the conveyance of water and solutes^[8].
The biosynthetic pathway of protolignin comes primarily from the breakthrough discovery and characterization of the enzymes that lead to monolignols syntheses of pcoumaryl, coniferyl, and sinapyl alcohols, whereby they form the hydroxyphenyl (H), guaiacyl (G), and syringyl (S) units in lignin, respectively. These units vary structurally due to different degrees of methoxy substituents^[7]. The xylem vessels in plants are known to provide both mechanical support and water conduction. These vessels are mainly composed of G-lignin and do not contain S-lignin since the enzymatic genes that encode for sinapyl alcohol are lacking in gymnosperms^[9].
Because G-lignin is lacking in angiosperms, additional specialized cells referred to as fiber cells provide much needed mechanical support^[10]. Fascinatingly, in angiosperms, these fiber cells are mainly composed of S-lignin. The genes involved in S-lignin synthesis developed much later than G-lignin, rendering evidence of evolution from softwood plants (gymnosperms) to hardwood plants (angiosperms)^[11]. Additionally, various plants commonly used as wood sources and crops with their lignin content identified. These Slignins are the source from which syringaldehyde can be obtained when lignocellulosic materials undergo certain oxidation reactions.

Extraction and isolations

The available percentage of precursors in the lignin structure strictly determines the formation of phenolic compounds such as vanillin or syringaldehyde. It becomes more useful in producing phenolic aldehydes when the lignin is subjected to fewer transformations or chemical treatments. In a study using lignin oxidation, in which the influence of lignin origin, condition of production, and type of pre-treatment on obtained yields of vanillin and syringaldehyde was inspected. The results indicated a competition between lignin fragments (syringyl fragments and guaiacyl fragments) condensation and lignin oxidation into aldehydes^[8]. It has been obtained a maximum yield of 14% for the total phenolic aldehydes (syringaldehyde + vanillin), based on nitrobenzene oxidation using lignin precipitated from kraft black liquor with the addition of a calcium salt dissolved in water soluble alcohol. In another study, a yield of about 50 to 59.7% syringaldehyde and vanillin in equal proportions of the total phenolic aldehydes was obtained via nitrobenzene oxidation from the lignin extracted from rice straw^[7].
Syringaldehyde has been reported to be separated and analyzed via a recrystallization process. A old study^[12] utilized the recrystallization process on the oxidation products of corn stems on one of the fractions using water and obtained syringaldehyde with a reported melting point of 110 to 112 °C. It was also reported that the oxidation of corn stems produced 3.2% crude yields and 2.6% pure syringaldehyde product. In a study of syringaldehyde composition in angiosperm monocotyledons and dicotyledons^[13], the recrystallization process was used in purifying the syringaldehyde sublimate. This study reported a yield of total phenolic aldehydes (vanillin and syringaldehyde) in monocotyledons between 21 to 30%, and dicotyledons between 39 and 48%.

Biological activity and applications

Advancements in analytical instruments coupled with breakthroughs in chemistry and pharmacology have allowed for the identification, quantification, and isolation of phenolic aldehydes for the diverse applications such as antioxidants, antifungal or antimicrobial, and anti-tumorigenesis agents in pharmaceuticals. In the food industry there is also a tendency to utilize naturally occurring flavor compounds that exhibit antioxidant and antimicrobial properties, hence providing a potential source of nonsynthetic preservatives and additives. Only preliminary in vitro tests have been reported in most cases, but a new potential research area and application of syringaldehyde has been identified. Keeping this in mind, some of the reported bioactive properties of syringaldehyde are exemplified here.
Antioxidant capacity
A study related to the structural motifs of syringaldehyde and other benzaldehydes for their antioxidant capabilities was approached by^[14]. In that study the presence of syringaldehyde in low quantities exhibited impressive results in peroxyl scavenging activity, based on the CB assay. Its antioxidant activity was recorded to be six times higher than that of protocatechuic aldehyde. The higher the Trolox equivalent value (TEV), the more antioxidant property a molecule will have. This value decreased in the order from syringaldehyde > protocatechuic aldehyde > vanillin. This method measures the ability of molecules with antioxidant properties to suppress ABTS, which is a blue-green chromophore exhibiting characteristic absorption at 734 nm. The suppression ability of the molecule is compared with that of Trolox, a vitamin-E analog. According to their study, the dimethoxy substitution in syringaldehyde as well as its syringol moiety was acknowledged for exhibiting enhanced antioxidant properties^[14].
Antimicrobial/antifungal activity
Fillat et al. (2012)^[15] studied the effects of non-leachable low molecular weight phenols with lactase on unbleached flax fibers in producing bio-modified pulp and paper. The researchers focus on the antimicrobial effect of syringaldehyde and acetosyringone (a derivative of syringaldehyde) in reducing the population of Staphylococcus aureus (Gram+), Klebsiella pneumonia (Gram-), and Pseudomonas aeruginosa (Gram-), which are known widely to cause diseases in humans. The population of Klebsiella pneumonia was reduced to 61% by syringaldehyde, whereas acetosyringone gave a major reduction up to 99%. In the case of Staphylococcus aureus, its reduction in population by syringaldehyde was 55%, which was 15% higher than acetosyringone. Another bacterium, Pseudomonas aeruginosa, was reduced by 71% using syringaldehyde and to a staggering 97% level by acetosyringone. The role of syringaldehyde as an antifungal agent against the medicinally important yeast Candida guilliermondii seems to be promising. It was reported that syringaldehyde successfully inhibited the C. guilliermondii growth rate and reduced xylitol production effectively. The fungicidal effect is most likely due to the aldehyde moiety. The hydroxyl substituent in syringaldehyde is suspected to play a key role in enhancing this fungicidal effect.^[16]
Mediator
Syringaldehyde was one of the first natural laccase mediators discovered. It has been reported to be used as a mediator in the degradation of indigo carmine by bacterial laccase (benzenediol oxygen oxidoreducase) obtained from the organism γ-Proteobacterium JB^[18]. The study ascertained that syringaldehyde was able to increase the degradation of indigo carmine by 57%. The enhanced degradation was made possible by the electron-donating methyl and methoxy substituents. Syringaldehyde is also used as a mediator in laccase-assisted biobleaching processes. In these processes, synthetic mediators such as HBT, violuric acid, and promazine were used. Another research focused on potentially cost-effective ligninderived natural mediators, including syringaldehyde obtained from spent pulping liquors and plant materials used in the paper pulp laccase-mediator delignification process in combination with peroxide bleaching^[17].
Organic markers in wood smoke
For confirmation of carbon-based fractions in smoke emissions, biomarkers or molecular tracers are employed as indicators to detect the origins from natural products of vegetation and their post-combustion residuals. Phenolic compounds (like syringaldehyde), which are obtained from lignin pyrolysis in vegetation, have been proposed as tracers specific for plant taxonomy. Syringaldehyde is widely used as a molecular marker for biomass smoke from aerosol particulate matter, namely to monitor pollution sources and detect the extent of combustion^[19]. Since global climate change is affecting the occurrence of wildfires, a need to quantitatively identify atmospheric particulate matter from smoke appears to be of grave importance^[20]. Syringaldehyde seems to play a key role in the detection of hardwood smoke.
Biological control activity
Syringaldehyde has been reported as an Agrobacterium tumefaciens virulence gene inducer. A study on the insecticidal properties of syringaldehyde was carried out on Acanthoscelides obtectus beetles^[21]. Syringaldehyde showed a significant decrease in natural mobility by the 4th day and caused significant mortality on the 8th day. An investigation utilizing spectrophotometric analysis to determine amino acids using syringaldehyde was also reported ^[22]. A simple and sensitive spectrophotometric method was developed for kinetic determination of amino acids through their condensation with syringaldehyde. This provides an additional option in the analysis of amino acids with advantages of reagent availability, reagent stability, and less time consumption.

References

1. Vergnenegre, A. (2001). Revue des Maladies Respiratoires 18(5), 507-16.
2. Garrote, G., et al (2004). Trends in Food Science & Technology 15, 191-200.
3. Bortolomeazzi, R., et al (2001) Food Chemistry 100(4), 1481-1489.
4. Rouche, H.-L. (1978). US Patent 4,115,650.
5. Xiang, Q., and Lee, Y. (2001). Applied Biochemistry and Biotechnology 91-93(1), 71-80.
6. Kleinert, M., and Barth, T. (2008). Energy & Fuels 22, 13711379.
7. Christiernin, M., et al (2005). Plant Physiology and Biochemistry 43(8), 777-785.
8. Hacke, U. G., and Sperry, J. S. (2001). Evolution and Systematics 4(2), 97-115.
9. Boerjan, W., et al (2003). Annu Rev Plant Biol 54(1), 519-546.
10. Fergus, B. J., et al (1970). Holzforschung 24(4), 113-117.
11. Li, L., et al (2001) Plant Cell 13(7), 1567-1586.
12. Creighton, R. H. J., et al (1941). JACS 63(1), 312.
13. Creighton, R. H. J., et al (1941). JACS 63(11), 3049-3052.
14. Boundagidou, O. G., et al (2010). Food Research International 43(8), 2014-2019.
15. Fillat, A., et al (2012). Carbohydrate Polymers 87(1), 146-152.
16. Kelly, C., et al (2008). In: Biotechnology for Fuels and Chemicals, Humana Press, 615-626.
17. Camarero, S., et al (2007). Enzyme and Microbial Technology 40(5), 1264-1271.
18. Singh, G., et al (2007). Enzyme and Microbial Technology 41, 794-799.
19. Robinson, A. L., et al (2006). Environmental Science & Technology 40(24), 7811-7819
20. Simoneit, B. R. T. (2002). Applied Geochemistry 17, 129-162.
21. Regnault-Roger, C., et al (2004). Journal of Stored Products Research 40(4), 395-408.
22. Medien, H. A. A. (1998). " Spectrochimica Acta Part A.: Molecular and Biomolecular Spectroscopy, 54(2), 359-365

 

Description

Syringaldehyde is an important constituent of many plant isolates and has widespread occurrence in wood products. It can be easily converted to trimethoxy-benzaldehyde which is an essential intermediate of the antibacterial drug trimethoprim. It is also used in the colorimetric determination of free chlorine in water.

Physical properties

light yellow-green to brown crystalline powder.

Chemical Properties

4-Hydroxy-3,5-dimethoxybenzaldehyde has sweet, balsamic-floral odor of considerable tenacity. lt has notes in common with Vanillin but is not as sweet and not as Vanilla-like, more floral and slightly greener.

Occurrence

Reported found in pineapple, beer, wine, grape brandy, rum, many different whisky products, sherry, roasted barley and hardwood smoke

Uses

Syringaldehyde may be used as an analytical reference standard for the determination of the analyte in guacoextracts and pharmaceutical preparations,(1) cognacs and wines,(2) plum brandies,(4) and wheat straw(5) by various chromatography techniques.

Uses

Syringaldehyde is used in biological studies for the isolation and structural characterization of milled wood lignin, dioxane lignin, and cellulolytic lignin preparation from Brewer''s spent grain.

Preparation

Vanillin is converted to 5-iodovanillin, which is treated with sodium methoxide to form 4-hydroxy-3,5- dimethyxybenzaldehyde.

Definition

ChEBI: A hydroxybenzaldehyde that is 4-hydroxybenzaldehyde substituted by methoxy groups at positions 3 and 5. Isolated from Pisonia aculeata and Panax japonicus var. major, it exhibits hypoglycemic activity.

Aroma threshold values

Aroma characteristics at 1.0%: weak sweet, slightly smoky, cinnamic, vanilla, leather-like with a phenolic medicinal nuance

Synthesis Reference(s)

Canadian Journal of Chemistry, 31, p. 476, 1953 DOI: 10.1139/v53-064
Synthetic Communications, 20, p. 2659, 1990 DOI: 10.1080/00397919008051474

General Description

Syringaldehyde is an aromatic phenolic aldehyde and a degradation product of lignin. It exhibits antioxidant activity and is reported to inhibit prostaglandin synthetase enzyme. The synthetic form of syringaldehyde is commercially used in pharmaceuticals, food, cosmetics, textiles, pulp and paper industries.

Biochem/physiol Actions

Odor at 1.0%

Purification Methods

Crystallise syringaldehyde from pet ether. [Beilstein 8 H 391, 8 IV 2718.]