Department of Biology, University of Massachusetts, Boston, MA 02125, USA.
Department of Chemistry, University of Massachusetts, Boston, MA 02125, USA.
Int J Mol Sci. 2020 Sep 15;21(18):6774. doi: 10.3390/ijms21186774.
The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational leukoderma. RK is a carbonyl derivative of 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause leukoderma in skin of many consumers. These two phenolic compounds are oxidized by tyrosinase and the resultant products seem to cause cytotoxicity to melanocytes by producing reactive oxygen species and depleting cellular thiols through -quinone oxidation products. Therefore, it is important to understand the biochemical mechanism of the oxidative transformation of these compounds. Earlier studies indicate that RK is initially oxidized to RK quinone by tyrosinase and subsequently converted to a side chain desaturated catechol called 3,4-dihydroxybenzalacetone (DBL catechol). In the present study, we report the oxidation chemistry of DBL catechol. Using UV-visible spectroscopic studies and liquid chromatography mass spectrometry, we have examined the reaction of DBL catechol with tyrosinase and sodium periodate. Our results indicate that DBL quinone formed in the reaction is extremely reactive and undergoes facile dimerization and trimerization reactions to produce multiple isomeric products by novel ionic Diels-Alder type condensation reactions. The production of a wide variety of complex quinonoid products from such reactions would be potentially more toxic to cells by causing not only oxidative stress, but also melanotoxicity through exhibiting reactions with cellular macromolecules and thiols.
人体皮肤暴露于 4-(4-羟苯基)-2-丁酮（覆盆子酮，RK）会导致化学性/职业性白斑病。RK 是 4-(4-羟苯基)-2-丁醇（杜鹃醇）的羰基衍生物，杜鹃醇是一种皮肤增白剂，已被发现会导致许多消费者的皮肤出现白斑病。这两种酚类化合物可被酪氨酸酶氧化，其产物似乎通过产生活性氧和通过醌氧化产物耗竭细胞硫醇，对黑色素细胞造成细胞毒性。因此，了解这些化合物的氧化转化的生化机制非常重要。早期研究表明，RK 最初被酪氨酸酶氧化为 RK 醌，然后转化为一种侧链不饱和的邻苯二酚，称为 3,4-二羟基苯丙醛（DBL 邻苯二酚）。在本研究中，我们报告了 DBL 邻苯二酚的氧化化学。通过紫外可见光谱研究和液相色谱质谱联用，我们研究了 DBL 邻苯二酚与酪氨酸酶和高碘酸钠的反应。我们的结果表明，反应中形成的 DBL 醌非常活泼，通过新型离子 Diels-Alder 型缩合反应，容易发生二聚和三聚反应，生成多种异构产物。这些反应产生的各种复杂的醌类产物不仅会引起氧化应激，还会通过与细胞大分子和硫醇反应，对细胞表现出黑色素毒性，从而可能对细胞造成更大的毒性。
