5739-85-5Relevant academic research and scientific papers
Stereoselective total synthesis of (?)-pyrenophorin
Edukondalu, Perugu,Sreenivasulu, Reddymasu,Raju, Rudraraju Ramesh
, p. 2945 - 2950 (2020)
Abstract: Stereoselective total synthesis of (?)-pyrenophorin was accomplished from commercially available starting material 2-bromo epoxide using regioselective ring opening and the intermolecular Mitsunobu cyclization as key steps. Graphic abstract: [Figure not available: see fulltext.].
Stereoselective total synthesis of (-)-pyrenophorin
Ramakrishna, Kolluri,Sreenivasulu, Reddymasu,Vidavalur, Siddaiah,Reddy, Boggu Jagan Mohan
, p. 693 - 697 (2016)
Background: Homo and hetero dimers of macrodilacto cyclic compounds were observed frequently in nature and they were built with different types of functional groups, chemical skeletons and ring sizes. Natural products with macrodiolide frameworks are also known to exhibit a wide range of biological properties including antibiotic, antifungal, antihelmintic, phytotoxic, and antileukemic activities. The main aim of this paper was the stereoselective total synthesis of (-)-Pyrenophorin from commercially available starting material (S)-propylene oxide with high yields. Methods: Stereoselective total synthesis of (-)-Pyrenophorin was done by hydrolytic kinetic resolution, Wittig olefination followed by Mitsunobu reaction. Results: The disconnection approach analysis (retrosynthetic) of (-)-Pyrenophorin envisions that it would be synthesized through the hydroxyl-acid via cyclo dimerisation under the Mitsunobu reaction conditions and followed by deprotection of cyclic ketals. Hydroxy-acid would be achieved from alcohol, while the alcohol would be obtained from (S)-propylene oxide. Conclusion: The total synthesis of target molecules achieved from commercially available starting materials, soft reaction conditions, decrease of reaction conditions and high purities with large yields. These type of biologically potent target molecules total synthesis was very important in industrial point of view.
Macrodiolide Diversification Reveals Broad Immunosuppressive Activity That Impairs the cGAS-STING Pathway
Biltoft, Mette,Jakobsen, Martin R.,Jennet, Kira M.,Kristensen, Tobias F.,Liu, Han,Ottosen, Rasmus N.,Poulsen, Thomas B.,Svenningsen, Esben B.
, p. 18734 - 18741 (2021/07/19)
The development of new immunomodulatory agents can impact various areas of medicine. In particular, compounds with the ability to modulate innate immunological pathways hold significant unexplored potential. Herein, we report a modular synthetic approach to the macrodiolide natural product (?)-vermiculine, an agent previously shown to possess diverse biological effects, including cytotoxic and immunosuppressive activity. The synthesis allows for a high degree of flexibility in modifying the macrocyclic framework, including the formation of all possible stereoisomers. In total, 18 analogues were prepared. Two analogues with minor structural modifications showed clearly enhanced cancer cell line selectivity and reduced toxicity. Moreover, these compounds possessed broad inhibitory activity against innate immunological pathways in human PBMCs, including the DNA-sensing cGAS-STING pathway. Initial mechanistic characterization suggests a surprising impairment of the STING-TBK1 interaction.
Diversity of antimicrobial pyrenophorol derivatives from an endophytic fungus, Phoma sp.
Zhang, Wen,Krohn, Karsten,Egold, Hans,Draeger, Siegfried,Schulz, Barbara
experimental part, p. 4320 - 4328 (2009/04/11)
Pyrenophorol (1) and (-)-dihydropyrenophorin (3), two known macrodiolides, were isolated together with four new analogues (2, 4-6) and three ring-opened derivatives (7-9) from Phoma sp., an endophytic fungus isolated from Lycium intricatum from Gomera. The structures of the new compounds were elucidated by detailed spectroscopic analysis, comparison with reported data, and chemical interconversion. The absolute configurations were determined by chemical correlations and a modified Mosher's method. The diversity of these seven newly discovered metabolites not only extends the pyrenophorol macrocyclic family, but also gives insight into the biosynthetic interconnections, in particular by isolation of the open-chain precursors. Preliminary studies showed antimicrobial activity of these compounds against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
Formation of macrocycles via ring-closing olefin metathesis
Choon Woo Lee,Grubbs
, p. 7155 - 7158 (2007/10/03)
The enhanced metathesis activity of 1,3-dimesityl-4,5-dihydroimidazole-2-ylidene ruthenium carbene catalyst 3 significantly increases the feasibility of synthesizing macrocyclic compounds. Catalyst 3 exhibits sufficient activity in RCM to dimerize α,β-unsaturated ester substrates and afford the corresponding head-to-tail (E,E)-dimeric (and trimeric) macrocycles. The dimerization appears to be under thermodynamic control with the product mixture dependent not only on the electronic and steric nature of the substrate but also on concentration.
Exploiting the reversibility of olefin metathesis. Syntheses of macrocyclic trisubstituted alkenes and (R,R)-(-)-pyrenophorin.
Fuerstner,Thiel,Ackermann
, p. 449 - 451 (2007/10/03)
[figure: see text] The formation of the trisubstituted cycloalkene 7 by RCM of diene 5 proceeds via the acyclic dimer 6, thus demonstrating the ready reversibility of olefin metathesis if catalyzed by "second generation" ruthenium carbene complexes such as 2-4. When applied to acrylate 11, these catalysts trigger a cyclooligomerization process that evolves with time and serves as key step en route to the lactide antibiotic (-)-pyrenophorin 8.
A Nitrile Oxide Cycloaddition Approach to (-)-Pyrenophorin, and Rosefuran.
Barco, Achille,Benetti, Simonetta,Risi, Carmela De,Pollini, Gian P.,Zanirato, Vinicio
, p. 7721 - 7726 (2007/10/02)
Nitrile oxide cycloaddition chemistry has been conveniently applied as carbon-carbon bond forming reaction for the assemblage of the functionalized carbon atom fragments required for the synthesis of two simple but different targets such as the macrolide antibiotic (-)-pyrenophorin 1 and rosefuran 2, a trace component of the high prized oil of rose.In both cases, an intermediate 3,5-disubstituted isoxazoline ring system has been used as serviceable precursor of the the salient structural feature of the targets, namely a γ-oxoacrylate moiety, common to many biologically active compounds, and a β,γ-dihydroxyketone functionality, easily converted by mild acid treatment to rosefuran.
A New Approach to the Synthesis of γ-Hydroxy-α,β-unsaturated Macrolides and (-)-Pyrenophorin by Intramolecular C=C Bond Formation with Oxidative Functionalization from ω-alkanal
Nokami, Junzo,Taniguchi, Takuya,Gomyo, Shintaro,Kakihara, Toshio
, p. 1103 - 1106 (2007/10/02)
The title compounds were prepared via the intramolecular condensation reaction of 12-tridecanal(or dodecanal) or via the combination of inter- and intramolecular condensation of 5-hexanal in the presence of piperidine.
Total Synthesis of (-)-Pyrenophorin via Cobalt(II) Porphyrin-Catalyzed Oxygenation of Ethyl (2E,4E,7R)-7-Acetoxy-2,4-octadienoate
Matsushita, Yoh-ichi,Furusawa, Hiroshi,Matsui, Takanao,Nakayama, Mitsuru
, p. 1083 - 1084 (2007/10/02)
(-)-Pyrenophorin was synthesized by the Mitsunobu reaction of (2E,7S)-4,4-ethylenedioxy-7-hydroxy-2-octenoic acid which has been prepared via cobalt(II) porphyrin-catalyzed oxygenation of ethyl (2E,4E,7S)-7-acetoxy-2,4-octadienoate.
Preparation of macrodiolides via a common chiral building block. Total synthesis of (-)-pyrenophorin and (-)-pyrenophorol
Machinaga, Nobuo,Kibayashi, Chihiro
, p. 841 - 844 (2007/10/02)
Macrodiolides (-)-pyrenophorin and (-)-pyrenophorol have been synthesized utilizing a C2 symmetric (R,R)-diepoxide as a common enantiopure chiral building block.
