TY - JOUR A1 - Kwesiga, George A1 - Sperlich, Eric A1 - Schmidt, Bernd T1 - Scope and applications of 2,3-oxidative aryl rearrangements for the synthesis of isoflavone natural products JF - The journal of organic chemistry N2 - The reaction of flavanones with hypervalent iodine reagents was investigated with a view to the synthesis of naturally occurring isoflavones. In contrast to several previous reports in the literature, we did not observe the formation of any benzofurans via a ring contraction pathway, but could isolate only isoflavones, resulting from an oxidative 2,3-aryl rearrangement, and flavones, resulting from an oxidation of the flavanones. Although the 2,3-oxidative rearrangement allows a synthetically useful approach toward some isoflavone natural products due to the convenient accessibility of the required starting materials, the overall synthetic utility and generality of the reaction appear to be more limited than previous literature reports suggest. Y1 - 2021 U6 - https://doi.org/10.1021/acs.joc.1c01375 SN - 0022-3263 SN - 1520-6904 VL - 86 IS - 15 SP - 10699 EP - 10712 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Sperlich, Eric A1 - Kelling, Alexandra A1 - Kwesiga, George A1 - Schmidt, Bernd T1 - Intermolecular interactions in the solid-state structures of isoflavones BT - the relationship between supramolecular structure, torsion angle, and macroscopic properties JF - CrystEngComm / The Royal Society of Chemistry N2 - The molecular structures of three closely related isoflavones have been determined by single crystal X-ray diffraction and have been analysed by geometry matching with the CSD, Hirshfeld surface analysis and analysis of stacking interactions with the Aromatic Analyser program (CSD). The formation of the supramolecular structure by non-covalent interactions was studied and substantial differences in the macroscopic properties e.g., the solubility, were correlated with hydrogen bonding and pi-stacking interactions. Moreover, a correlation between the supramolecular structure, the torsion angle (between benzopyran group and aryl group), and macroscopic properties was determined in the three compounds. Y1 - 2022 U6 - https://doi.org/10.1039/d2ce00169a SN - 1466-8033 VL - 24 IS - 26 SP - 4731 EP - 4739 PB - Royal Society of Chemistry CY - London ER - TY - THES A1 - Kwesiga, George T1 - Synthesis of isoflavonoids from African medicinal plants with activity against tropical infectious diseases T1 - Synthese von Isoflavonoiden aus afrikanischen Heilpflanzen mit Wirkung gegen tropische Infektionskrankheiten N2 - Two approaches for the synthesis of prenylated isoflavones were explored: the 2,3-oxidative rearrangement/cross metathesis approach, using hypervalent iodine reagents as oxidants and the Suzuki-Miyaura cross-coupling/cross metathesis approach. Three natural prenylated isoflavones: 5-deoxy-3′-prenylbiochanin A (59), erysubin F (61) and 7-methoxyebenosin (64), and non-natural analogues: 7,4′-dimethoxy-8,3′-diprenylisoflavone (126j) and 4′-hydroxy-7-methoxy-8,3′-diprenylisoflavone (128) were synthesized for the first time via the 2,3-oxidative rearrangement/cross metathesis approach, using mono- or diallylated flavanones as key intermediates. The reaction of flavanones with hypervalent iodine reagents afforded isoflavones via a 2,3-oxidative rearrangement and the corresponding flavone isomers via a 2,3-dehydrogenation. This afforded the synthesis of 7,4′-dimethoxy-8-prenylflavone (127g), 7,4′-dimethoxy-8,3′-diprenylflavone (127j), 7,4′-dihydroxy-8,3′-diprenylflavone (129) and 4′-hydroxy-7-methoxy-8,3′-diprenylflavone (130), the non-natural regioisomers of 7-methoxyebenosin, 126j, erysubin F and 128 respectively. Three natural prenylated isoflavones: 3′-prenylbiochanin A (58), neobavaisoflavone (66) and 7-methoxyneobavaisoflavone (137) were synthesized for the first time using the Suzuki-Miyaura cross-coupling/cross metathesis approach. The structures of 3′-prenylbiochanin A (58) and 5-deoxy-3′-prenylbiochanin A (59) were confirmed by single crystal X-ray diffraction analysis. The 2,3-oxidative rearrangement approach appears to be limited to the substitution pattern on both rings A and B of the flavanone while the Suzuki-Miyaura cross-coupling approach appears to be the most suitable for the synthesis of simple isoflavones or prenylated isoflavones whose prenyl substituents or allyl groups, the substituents that are essential precursors for the prenyl side chains, can be regioselectively introduced after the construction of the isoflavone core. The chalcone-flavanone hybrids 146, 147 and 148, hybrids of the naturally occurring bioactive flavanones liquiritigenin-7-methyl ether, liquiritigenin and liquiritigenin-4′-methyl ether respectively were also synthesized for the first time, using Matsuda-Heck arylation and allylic/benzylic oxidation as key steps. The intermolecular interactions of 5-deoxy-3′-prenylbiochanin A (59) and its two closely related precursors 106a and 106b was investigated by single crystal and Hirshfeld surface analyses to comprehend their different physicochemical properties. The results indicate that the presence of strong intermolecular O-H···O hydrogen bonds and an increase in the number of π-stacking interactions increases the melting point and lowers the solubility of isoflavone derivatives. However, the strong intermolecular O-H···O hydrogen bonds have a greater effect than the π-stacking interactions. 5-Deoxy-3′-prenylbiochanin A (59), erysubin F (61) and 7,4′-dihydroxy-8,3′-diprenylflavone (129), were tested against three bacterial strains and one fungal pathogen. All the three compounds were 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 isoflavone erysubin F (61) and its flavone isomer 129 showed in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) at MIC values of 15.4 and 20.5 μM, respectively. 5-Deoxy-3′-prenylbiochanin A (59) was inactive against this MRSA strain. Erysubin F (61) and its flavone isomer 129 could serve as lead compounds for the development of new alternative drugs for the treatment of MRSA infections. N2 - Ziel dieser Studie war es, aus afrikanischen Heilpflanzen isolierte Naturstoffe künstlich herzustellen, die zur Behandlung tropischer Infektionskrankheiten wie Malaria und bakterieller Infektionen eingesetzt werden, um Schlüsselsubstanzen für die Entwicklung neuer Medikamente zu identifizieren. Sechs Naturstoffe aus afrikanischen Heilpflanzen wie dem Korallenbaum (Erythrina-species) wurden erstmals künstlich hergestellt. Bei der Herstellung dieser Naturstoffe wurden auch sechs weitere verwandte nicht-natürliche Analoga hergestellt. Zwei Naturstoffe (5-Deoxy-3′-prenylbiochanin A und Erysubin F) aus dem Korallenbaum (Erythrina sacleuxii) und eine verwandte nicht-natürliche Substanz wurden auf ihre antimikrobielle Aktivität gegen drei Bakterienstämme und einen Pilzstamm getestet. Alle drei Substanzen waren nicht wirksam gegen Escherichia coli, ein Bakterium, das Harnwegsinfektionen und Durchfall verursacht; Salmonella entrica, das Typhus verursacht, und Candida albicans, das Candidiasis verursacht. Erysubin F und sein nicht-natürliches Analogon waren sehr aktiv gegen Methicillin-resistente Staphylococcus aureus (MRSA), ein Bakterium, das hauptsächlich in sehr geringen Konzentrationen Hautinfektionen verursacht. 5-Deoxy-3'-prenylbiochanin A war gegen diesen MRSA-Stamm nicht aktiv. Erysubin F und sein nicht-natürliches Analogon könnten als Schlüsselsubstanzen für die Entwicklung eines neuen Medikaments gegen Infektionen durch MRSA dienen. KW - synthesis KW - isoflavonoids KW - African medicinal plants KW - tropical infectious diseases KW - Afrikanische Heilpflanzen KW - Isoflavonoide KW - Synthese KW - tropische Infektionskrankheiten Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-559069 ER - TY - JOUR A1 - Kwesiga, George A1 - Kelling, Alexandra A1 - Kersting, Sebastian A1 - Sperlich, Eric A1 - von Nickisch-Rosenegk, Markus A1 - Schmidt, Bernd T1 - Total syntheses of prenylated isoflavones from Erythrina sacleuxii and their antibacterial activity BT - 5-deoxy-3′-prenylbiochanin A and erysubin F JF - Journal of natural products N2 - 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 mu M. 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 mu M, respectively. In contrast, the monoprenylated 5-deoxy-3'-prenylbiochanin A (7) is inactive against this MRSA strain. Y1 - 2020 U6 - https://doi.org/10.1021/acs.jnatprod.0c00932 SN - 0163-3864 SN - 1520-6025 VL - 83 IS - 11 SP - 3445 EP - 3453 PB - American Chemical Society CY - Washington ER -