Ellinwood Duncan C, El-Mansy Mohamed F, Plagmann Layhna S, Stevens Jan F, Maier Claudia S, Gombart Adrian F, Blakemore Paul R
Department of Chemistry, Oregon State University, Corvallis, OR, USA.
National Research Centre, Department of Organometallic and Organometalloid Chemistry, Cairo, Dokki, Egypt.
J Labelled Comp Radiopharm. 2017 Dec;60(14):639-648. doi: 10.1002/jlcr.3571. Epub 2017 Nov 20.
Xanthohumol [(E)-6'-methoxy-3'-(3-methylbuten-2-yl)-2',4',4″-trihydroxychalcone], he principal prenylated flavonoid from hops, has a complex bioactivity profile, and C-labeled isotopomers of this compound are of potential use as molecular probes and as analytical standards to study metabolism and mode of action. 1,3-[ C] -Xanthohumol was prepared by an adaptation of the total synthesis of Khupse and Erhardt in 7 steps and 5.7% overall yield from phloroglucinol by a route incorporating a cascade Claisen-Cope rearrangement to install the 3'-prenyl moiety from a 5'-prenyl aryl ether and an aldol condensation between 1-[ C]-2',4'-bis(benzyloxymethyloxy)-6'-methoxy-3'-(3-methylbuten-2-yl)acetophenone and 1'-[ C]-4-(methoxymethyloxy)benzaldehyde. The C-atom in the methyl ketone was derived from 1-[ C]-acetyl chloride while that in the aryl aldehyde was derived from [ C]-iodomethane. Tri- and penta- C-labeled xanthohumols were similarly prepared by applying minor modifications to the route.
黄腐酚[（E）-6'-甲氧基-3'-（3-甲基丁-2-烯基）-2'，4'，4''-三羟基查耳酮]是啤酒花中主要的异戊烯基黄酮，具有复杂的生物活性谱，该化合物的碳标记同位素异构体有潜力用作分子探针和分析标准品，以研究其代谢和作用方式。1,3-[¹³C]-黄腐酚是通过改进Khupse和Erhardt的全合成方法制备的，从间苯三酚出发，经7步反应，总产率为5.7%，其路线包括一个串联克莱森-科普重排反应，以从5'-异戊烯基芳基醚安装3'-异戊烯基部分，以及1-[¹³C]-2'，4'-双（苄氧基甲氧基）-6'-甲氧基-3'-（3-甲基丁-2-烯基）苯乙酮与1'-[¹³C]-4-（甲氧基甲氧基）苯甲醛之间的羟醛缩合反应。甲基酮中的碳原子来源于1-[¹³C]-乙酰氯，而芳醛中的碳原子来源于[¹³C]-碘甲烷。通过对该路线进行微小修改，类似地制备了三碳和五碳标记的黄腐酚。
