Total Synthesis of Plagiochin D by an Intramolecular S<sub>N</sub>Ar Reaction

Morales, Julio César Cortés; Torres, Alejandro Guillen; González‐Zamora, Eduardo

doi:10.1002/ejoc.201001412

Cited by 18 publications

(5 citation statements)

References 24 publications

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“… a Reagents and conditions: (a) THF, Et 3 SiH, cyclohexanone (77%); (b) Br 2 , HOAc (76%); (c) NaOH, THF, MeOH (99%); (d) CDI, THF; (e) N , N -dimethylsulfamide, DBU, THF (74%); (f) Pd(PPh 3 ) 4 , LiCl, Na 2 CO 3 , EtOH, toluene (88%); arylboronic acid aldehyde 7 was synthesized in four steps; (g) Cs 2 CO 3 , DMF (71%); (h) trimethylsulfoxonium iodide, NaH, DMSO (83%); (i) Chiracel-OJ chromatography, 44% recovery (50% theoretical); (j) NaOH, THF, MeOH, H 2 O (86%); (k) TBTU, DIPEA, DMF; (l) chromatography, MeOH, CH 2 Cl 2 (70%). …”

Section: Resultsmentioning

confidence: 99%

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

Bien

Davulcu

DelMonte

et al. 2018

Org. Process Res. Dev.

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The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkylation. Subsequent palladium-catalyzed intramolecular direct arylation efficiently builds the central seven-membered ring. The target was prepared in 12 linear steps with five isolations in an overall yield of 8%.

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Section: Resultsmentioning

confidence: 99%

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

Bien

Davulcu

DelMonte

et al. 2018

Org. Process Res. Dev.

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“…22 The double bond of each isomer was reduced with Wilkinson's catalyst to afford a single compound 14 ; the benzyl ether was retained under the mild hydrogenation conditions. 24 Subsequently, O -debenzylation was accomplished using concentrated HCl in HOAc to yield compound 15 , 18 and the free hydroxyl group was then converted to a triflate in 16 . 23 …”

Section: Chemistrymentioning

confidence: 99%

“…Macrocyclization to give 19 was achieved in 89% yield through an intramolecular S N Ar reaction using K 2 CO 3 in DMF at room temperature. Next, the nitro group was removed in a two-step sequence of reduction and deamination 18 to give plagiochin trimethyl ether ( 21 ). Plagiochin G ( 22 ) was finally obtained after cleavage of the methyl ethers.…”

Section: Chemistrymentioning

confidence: 99%

“…In 1999, Fukuyama et al 13, 14 used an intramolecular Still-Kelly reaction at position c to accomplish the macrocyclization in the syntheses of plagiochins A and D. “Plagiochin E”, initially reported as a natural product from the liverwort Marchantia polymorpha , 15 was totally synthesized in 2009 by Speicher et al, who revised the structure of the isolated “plagiochin E” to that of riccardin D. 16, 17 Subsequently, in 2010, Speicher et al reported the syntheses of plagiochins E−H by employing an intramolecular McMurry reaction at position a as the key macrocyclization step (Scheme 1). 11 In 2011, Cortes Morales et al 18 used an intramolecular S N Ar reaction at position d to form the 16-membered macrocyclic ring of plagiochin D (Scheme 1). Recently, Jiang et al prepared plagiochin E using an intramolecular McMurry reaction at position a for the macrocyclization (Scheme 1).…”

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confidence: 99%

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Total synthesis of plagiochin G and derivatives as potential cancer chemopreventive agents

Zhou

Tokuda

et al. 2014

Tetrahedron Letters

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A new and efficient total synthesis has been developed to obtain plagiochin G (22), a macrocyclic bisbibenzyl, and four derivatives. The key 16-membered ring containing biphenyl ether and biaryl units was closed via an intramolecular SNAr reaction. All synthesized macrocyclic bisbibenzyls inhibited Epstein-Barr virus early antigen (EBVEA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and, thus, are potential cancer chemopreventive agents.

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“…Cl 2 68,[109][110][111]. The combined organic extracts were dried (MgSO 4 ) and filtered, the filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography (25% EtOAc in hexanes) to afford bromide 106 (0.86 g, 98%) as a yellow solid.…”

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confidence: 99%

Synthesis of potential opioids based on the natural Pawhuskins

Gardner¹

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Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less. Marie Curie iii ACKNOWLEDGEMENTS To begin with, this thesis would not be here today if were not for the inspiration, given to me by my professors at Cal Poly Pomona, to continue my education with graduate school. I am incredibly grateful to have had Dr. David Wiemer as an advisor at the University of Iowa, as I value the considerable amount of knowledge and wisdom that he has bestowed on me during my time in graduate school. I cannot thank him enough for his continuous kindness, encouragement, and his extraordinary level of patience, it is truly admirable. Life in the lab would not have been the same without my fellow lab mates past and present. Thank you to Dr. John Kodet and all the other past students who continued to be of assistance beyond their time in the group. Particular thanks should go to Dr. Alyssa Hartung for her guidance when I started my work in the lab and providing several samples for my pawhuskin research, as well as Dr. Jeffrey Neighbors for testing my compounds and his continued collaboration. I would like to thank Carrie Meyers for her assistance in the lab as an undergraduate researcher. For Dr. Veronica Wills, Dr. Rebekah Shippy, and the current students, I am appreciative of all of your support through the new friendships I have formed and for always being there to help solve problems in the lab. The faculty and staff of the Department of Chemistry have been profoundly helpful and supportive throughout my time here in Iowa. I am very grateful for all that they do and for my fellow students in the department who have helped make my graduate iv school experience that much more enjoyable. I would also like to thank the Roy J. Carver Trust for the financial support that allowed me to spend more time in the lab. This journey would have been more trying if it were not for the relentless support and continued encouragement from my parents and the rest of my family. It was always reassuring to know that they were constantly right behind me, cheering me on. Last, but certainly not least, I want to thank my wonderful husband for his constant encouragement and support. Throughout my years in graduate school, he has always been understanding of all the time I have spent in the lab and on my computer at home; and often found ways to help me dedicate even more time towards research. He is incredibly patient, especially when I talk endlessly about chemistry. I have always enjoyed his take on what I do; even when he constantly reminds me that a geranyl chain resembles a staircase. Thank you, Joe, for being one of my biggest supporters, and always finding ways to bring laughter into every single one of my days.

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Total Synthesis of Plagiochin D by an Intramolecular S_NAr Reaction

Cited by 18 publications

References 24 publications

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

Total synthesis of plagiochin G and derivatives as potential cancer chemopreventive agents

Synthesis of potential opioids based on the natural Pawhuskins

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Total Synthesis of Plagiochin D by an Intramolecular SNAr Reaction

Cited by 18 publications

References 24 publications

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

Total synthesis of plagiochin G and derivatives as potential cancer chemopreventive agents

Synthesis of potential opioids based on the natural Pawhuskins

Contact Info

Product

Resources

About

Total Synthesis of Plagiochin D by an Intramolecular S_NAr Reaction