Raspberry ketone occurs in a variety of fruits, including raspberries, cranberries, and blackberries.[3] It is detected and released by orchid flowers, e.g. Dendrobium superbum (syn D. anosmum),[4] and several Bulbophyllum species[5][6][7] to attract raspberry ketone-responsive male Dacini fruit flies. It is biosynthesized from coumaroyl-CoA.[8] It can be extracted from the fruit, yielding about 1–4 mg per kg of raspberries.[9]
Preparation
Since the natural abundance of raspberry ketone is very low, it is prepared industrially by a variety of methods from chemical intermediates.[10] One of the ways this can be done is through a Claisen-Schmidt condensation followed by catalytic hydrogenation. First, acetone is condensed with 4-hydroxybenzaldehyde to form an α,β-unsaturated ketone. Then the alkene part is reduced to the alkane. This two-step method produces raspberry ketone in 99% yield.[11] There is a less expensive hydrogenation catalyst, nickel boride, which also demonstrates high selectivity towards hydrogenation of the double bond of enone.[12]
Uses
Raspberry ketone is sometimes used in perfumery, in cosmetics, and as a food additive to impart a fruity odor. It is one of the most expensive natural flavor components used in the food industry. The natural compound can cost as much as $20,000 per kg.[9]
Marketing
Although products containing this compound are marketed for weight loss, there is no clinical evidence for this effect in humans.[13][14] They are called "ketones" because of the ketone (acetone) group at their end, which is shared with ketone bodies.
Safety
Little is known about the long-term safety of raspberry ketone supplements,[15][16] especially since little research has been done with humans.[17] Toxicological models indicate a potential for cardiotoxic effects, as well as effects on reproduction and development.[15] Furthermore, in many dietary supplements containing raspberry ketones, manufacturers add other ingredients such as caffeine which may have unsafe effects.[17]
^Nishida, R.; Iwahashi, I.; Tan, K.H. (1993). "Accumulation of Dendrobium (Orchidaceae) flower fragrance in the rectal glands by males of the melon fly, Dacus cucurbitae (Tephritidae)". Journal of Chemical Ecology. 19: 713–722. doi:10.1007/BF00985003.
^Tan, K.H.; Nishida, R. (2005). "Synomone or Kairomone? - Bulbophyllum apertum (Orchidaceae) flower releases raspberry ketone to attract Bactrocera fruit flies". Journal of Chemical Ecology. 31 (3): 509–519. doi:10.1007/s10886-005-2023-8.
^Nakahira, M.; Ono, H.; Wee, S.L.; Nishida, R. (2018). "Floral synomone diversification of Bulbophyllum sibling species (Orchidaceae) in attracting fruit fly pollinators". Biochemical Systematics and Ecology. 81: 86–95. doi:10.1016/j.bse.2018.10.002. hdl:2433/235528.
^ abBeekwilder, Jules; Van Der Meer, Ingrid M.; Sibbesen, Ole; Broekgaarden, Mans; Qvist, Ingmar; Mikkelsen, Joern D.; Hall, Robert D. (2007). "Microbial production of natural raspberry ketone". Biotechnology Journal. 2 (10): 1270–9. doi:10.1002/biot.200700076. PMID17722151. S2CID32088996.
^Tateiwa, Jun-Ichi; Horiuchi, Hiroki; Hashimoto, Keiji; Yamauchi, Takayoshi; Uemura, Sakae (1994). "Cation-Exchanged Montmorillonite-Catalyzed Facile Friedel-Crafts Alkylation of Hydroxy and Methoxy Aromatics with 4-Hydroxybutan-2-one to Produce Raspberry Ketone and Some Pharmaceutically Active Compounds". The Journal of Organic Chemistry. 59 (20): 5901–4. doi:10.1021/jo00099a017.
^Smith, Leverett R. (1996). "Rheosmin ('Raspberry Ketone') and Zingerone, and Their Preparation by Crossed Aldol-Catalytic Hydrogenation Sequences". The Chemical Educator. 1 (3): 1–18. doi:10.1007/s00897960034a. S2CID94729547.
^ abBredsdorff L, Wedebye EB, Nikolov NG, Hallas-Møller T, Pilegaard K (2015). "Raspberry ketone in food supplements - High intake, few toxicity data - A cause for safety concern?". Regul Toxicol Pharmacol. 73 (1): 196–200. doi:10.1016/j.yrtph.2015.06.022. PMID26160596. S2CID38312188.