Synthesis of Natural Products on Solid Phases via Copper‐Mediated Coupling: Synthesis of the Aristogin Family, Spiraformin A, and Hernandial

Abstract

The formation of natural products on solid phases via diaryl ether coupling is presented herein. Starting with either commercially‐available or easily‐producible benzoic, cinnamic, or propionic acids, all immobilized on Merrifield resin via a pentane linker, copper‐mediated couplings yielded solid phase diaryl ethers in good yields. Both, phenol and resins containing aryl halides were used for these Ullmann‐type couplings to generate resin‐bound natural product derivatives. Through cleavage from the resin, eight naturally occurring substances isolated from Aristolochia elegans, Hernandia nymphaeifolia, Spiraea formosana, and Kandelia candel were prepared. To the best of our knowledge, four of these compounds, namely Aristogin D and F as well as Spiraformin A and compound 12 have never previously been synthesized. Gaining access to these natural products on solid supports, demonstrated the utility of diaryl ether formation for the development of combinatorial syntheses. Our approach to diaryl ethers on solid support offers the possibility of synthesizing libraries of natural product derivatives via combinatorial syntheses. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis and degranulation-inhibiting activities of the proposed apteniols B, C, and G

“…3) In 2014, we synthesized the compound reported as apteniol A (1), 4) and Jung and Bräse synthesized the compound reported as apteniol C (3) in 2009. 5) These two studies revealed that the spectral data for the isolated apteniols A (1) and C (3) slightly differed from those of the synthesized compounds. Moreover, DellaGreca et al described the conversion of apteniol B (2) to apteniol C (3) via esterification.…”

One‐Pot Synthesis of Novel Antiproliferative 9‐Aminoacridines

“…This suggested the necessity of harsher Ullmann conditions. [14] Synthesis of 9-(Arylamino)acridine Derivatives 2a,b by Using S N Ar Reactions…”

Diaryl Ether Formation in the Synthesis of Natural Products

“…1-2.4). Gerfelin, the aristogins, rodgersinol, the aspercyclides, and dictyomedin A. of human geranylgeranyl diphosphate (GGPP) synthase], [25] the aristogins (2-7), [26,27] rodgersinol (8, an iNOS and COX-2 inhibitor), [28,29] the aspercyclides (9-11, high-affinity IgE receptor inhibitors), [30][31][32][33] the dibenzofuran dictyomedin A (12), [34] and the various naturally occurring xanthones. Gerfelin, the aristogins, rodgersinol, the aspercyclides, and dictyomedin A. of human geranylgeranyl diphosphate (GGPP) synthase], [25] the aristogins (2-7), [26,27] rodgersinol (8, an iNOS and COX-2 inhibitor), [28,29] the aspercyclides (9-11, high-affinity IgE receptor inhibitors), [30][31][32][33] the dibenzofuran dictyomedin A (12), [34] and the various naturally occurring xanthones.…”

“…Both possible connection modes are observed ( Figure 4): cycloisodityrosine (19) and the potent antitumor antibiotics the RA alkaloids [e.g., bouvardin (20), RA-IV (21), RA-V or deoxybouvardin (22), and RA-VII (23)] exemplify one of them, whereas RP-66453 (24), a neurotensin receptor antagonist, is an example of the alternative ring closure mode. [17] Alternatively, the two tyrosine units can be separated by another amino acid, joining them either through the amino group of the phenol moiety and the carboxylic acid group of the aryl ether moiety, as in the angiotensin I converting enzyme inhibitor K-13 (25, Figure 5), or in the opposite sense, as in renieramide (26), the eurypamides (27)(28)(29), and the aminopeptidase B inhibitors OF-4949 I-IV (30). [17] Furthermore, the alkyl chain moieties of the original amino acids can be modified, as in the case of the antifungal agent piperazinomycin (31, Figure 6), [37][38][39][40] and the two aromatic rings can be decorated with additional substituents, such as bromine(s) in the case of the bastadins [17] [32-34, ryanodine (RyR) calcium channel modulators].…”