Total Syntheses of Prenylated Isoflavones from Erythrina sacleuxii and Their Antibacterial Activity: 5‑Deoxy-3′-prenylbiochanin A and Erysubin F

The prenylated isoflavones 5-deoxyprenylbiochanin A (7-hydroxy-4′-methoxy-3′-prenylisoflavone) and erysubin F (7,4′-dihydroxy-8,3′-diprenylisoflavone) were synthesized for the first time, starting from mono- or di-O-allylated chalcones, and the structure of 5-deoxy-3′-prenylbiochanin A was corroborated by single-crystal X-ray diffraction analysis. Flavanones are key intermediates in the synthesis. Their reaction with hypervalent iodine reagents affords isoflavones via a 2,3-oxidative rearrangement and the corresponding flavone isomers via 2,3-dehydrogenation. This enabled a synthesis of 7,4′-dihydroxy-8,3′-diprenylflavone, a non-natural regioisomer of erysubin F. Erysubin F (8), 7,4′-dihydroxy-8,3′-diprenylflavone (27), and 5-deoxy-3′-prenylbiochanin A (7) were tested against three bacterial strains and one fungal pathogen. All three compounds are inactive against Salmonella enterica subsp. enterica (NCTC 13349), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 90028), with MIC values greater than 80.0 μM. The diprenylated natural product erysubin F (8) and its flavone isomer 7,4′-dihydroxy-8,3′-diprenylflavone (27) show in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) at MIC values of 15.4 and 20.5 μM, respectively. In contrast, the monoprenylated 5-deoxy-3′-prenylbiochanin A (7) is inactive against this MRSA strain.本研究首次以单或二O-烯丙基化查尔酮为起始原料，成功合成了异戊烯基异黄酮类化合物5-脱氧异戊烯基鹰嘴豆芽素A（5-deoxyprenylbiochanin A，7-羟基-4′-甲氧基-3′-异戊烯基异黄酮）与erysubin F（7,4′-二羟基-8,3′-二异戊烯基异黄酮），并通过单晶X射线衍射分析确证了5-脱氧-3′-异戊烯基鹰嘴豆芽素A的结构。黄烷酮是该合成路线的关键中间体，其与高价碘试剂反应时，可通过2,3-氧化重排生成异黄酮，同时经由2,3-脱氢反应得到对应的黄酮异构体。借此策略，我们完成了7,4′-二羟基-8,3′-二异戊烯基黄酮的合成，该化合物为erysubin F的非天然区域异构体。我们对erysubin F（8）、7,4′-二羟基-8,3′-二异戊烯基黄酮（27）以及5-脱氧-3′-异戊烯基鹰嘴豆芽素A（7）开展了针对3种细菌菌株与1种真菌病原体的活性测试。结果显示，上述三种化合物对肠炎沙门氏菌肠炎亚种（Salmonella enterica subsp. enterica，NCTC 13349）、大肠埃希氏菌（Escherichia coli，ATCC 25922）以及白色念珠菌（Candida albicans，ATCC 90028）均无抑制活性，最低抑菌浓度（MIC）均大于80.0 μM。相较之下，二异戊烯基天然产物erysubin F（8）及其黄酮异构体7,4′-二羟基-8,3′-二异戊烯基黄酮（27）对耐甲氧西林金黄色葡萄球菌（MRSA，ATCC 43300）具有体外抑菌活性，其最低抑菌浓度分别为15.4 μM与20.5 μM。而单异戊烯基取代的5-脱氧-3′-异戊烯基鹰嘴豆芽素A（7）对该MRSA菌株无抑制活性。