Scientists in Italy have created an environmentally friendly method of making the principal bioactive compound found in royal jelly, a substance secreted by honeybees and fed to queen larvae to ensure that they develop into sexually mature females. They've also synthesised the compound the queen secretes that halts ovarian development in worker bees. And the compound from royal jelly has the potential to treat cancer or could be used as an active ingredient in health foods and cosmetics.
These biologically active compounds have been isolated from bees before, but the purification steps were complex and resulted in quantities too small for practical purposes. Researchers have also synthesised the compounds, but this required expensive and toxic reagents. Now, Sabrina Castellano at the University of Salerno, Fisciano, and colleagues have made 10-hydroxy-2E-decenoic acid (10-HDA, previously isolated from royal jelly) and 9-oxo-2E-decenoic acid (9-ODA, previously isolated from the queen's ovarian development inhibitor) on a gram scale, using a cheap, metal-free method.
The team used a TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl) catalysed oxidation of alcohols and then a Doebner-Knoevenagel reaction between the resulting aldehydes and malonic acid to produce the compounds.
'The compounds are being used in research to clarify their role in the phenotypical shift from worker to queen bees,' says Castellano. 'But there is much more than this: 10-HDA has several pharmacological activities, such as antitumor activity.' She adds that 10-HDA is exclusively contained in royal jelly. Its content - usually around 1.5-2% - dictates the quality of the royal jelly and it directly determines its price on the international market. And, because of its pharmacological properties, 10-HDA can be added to health food or cosmetics as an active ingredient.
'The stereoselective and environmentally friendly synthesis of 9-oxo- and 10-hydroxy-2(E)-decenoic acids is very important,' says Eleni Melliou, an expert in substances produced by bees from the University of Athens, Greece. 'These two acids are produced exclusively by honeybees and present significant bioactivity. Their isolation from natural sources is very difficult and expensive. Consequently, this synthesis is very useful because it can afford significant quantities, which are necessary for extensive pharmacological studies.'
- C Milite et al, RSC Adv., 2012, DOI: 10.1039/c2ra20275a