478183-68-5Relevant articles and documents
Genetic incorporation of a metal-chelating amino acid as a probe for protein electron transfer
Liu, Xiaohong,Li, Jiasong,Dong, Jianshu,Hu, Cheng,Gong, Weimin,Wang, Jiangyun
, p. 10261 - 10265,5 (2012)
ET encounters jellyfish: Through the incorporation of the metal-chelating amino acid pyTyr into green fluorescent protein (GFP) from jellyfish, photoinduced electron transfer (ET) from the GFP chromophore to a bound Cu II ion was shown to occur within one nanosecond in a distance-dependent manner. The crystal structure of GFP with pyTyr at a specific position shows the structural basis for the nanomolar binding affinity of pyTyr to CuII ions. Copyright
Total Synthesis and Bioactivity Mapping of Geodiamolide H
Arndt, Hans-Dieter,B??neck, Johanna,Bellstedt, Peter,Dahse, Hans-Martin,G?rls, Helmar,Küllmer, Florian,Nasufovi?, Veselin,Stallforth, Pierre
, p. 11633 - 11642 (2021/07/02)
The first total synthesis of the actin-stabilizing marine natural product geodiamolide H was achieved. Solid-phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the
Synthesis of Pentacyclic Framework of Herquline A
Kim, Thomas Taehyung,Lee, Chungwoo,Heo, Seongrok,Lee, Hee-Seung,Han, Sunkyu
supporting information, p. 3882 - 3885 (2021/10/14)
The highly strained bowl-shaped pentacyclic structure of herquline A has rendered it one of the most difficult problems in organic synthesis yet to be solved. The challenges associated with the synthesis of herquline A have been well documented in four Ph.D. dissertations and in multiple reports regarding syntheses of its structurally simpler congeners. Herein, we report the construction of the pentacyclic core of herquline A that contains both N10?C2 and C3?C3′ bonds. The key for success was the development of the tandem aza-Michael addition/enolate capture protocol that set the stage for subsequent palladium catalyzed C3(sp2)?C3′(sp2) coupling reaction. Ensuing oxidative dearomatization of the left aryl ring allowed the formation of the pentacyclic diketone core of herquline A.
Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling
Lang, Jan Hendrik,Lindel, Thomas
, p. 577 - 583 (2019/03/08)
The synthesis of the polyketide section present in the potently cytotoxic marine cyclodepsipeptide jasplakinolide and related natural products, geodiamolides and seragamides, is reported. The key step is a Negishi cross coupling of (R)-(3-methoxy-2-methyl
Concise Total Synthesis of Herqulines B and C
He, Chi,Stratton, Thomas P.,Baran, Phil S.
supporting information, p. 29 - 32 (2019/01/16)
A simple total synthesis of herqulines B and C is reported, modeled on the reductive biosynthesis reported previously by other researchers. Commencing from tyrosine, these alkaloids were fashioned through a dimerization, macrocyclization, and four consecu
Structure-Activity Relationships of cyclo(l -Tyrosyl- l -tyrosine) Derivatives Binding to Mycobacterium tuberculosis CYP121: Iodinated Analogues Promote Shift to High-Spin Adduct
Rajput, Sunnia,McLean, Kirsty J.,Poddar, Harshwardhan,Selvam, Irwin R.,Nagalingam, Gayathri,Triccas, James A.,Levy, Colin W.,Munro, Andrew W.,Hutton, Craig A.
supporting information, p. 9792 - 9805 (2019/11/13)
A series of analogues of cyclo(l-tyrosyl-l-tyrosine), the substrate of the Mycobacterium tuberculosis enzyme CYP121, have been synthesized and analyzed by UV-vis and electron paramagnetic resonance spectroscopy and by X-ray crystallography. The introduction of iodine substituents onto cyclo(l-tyrosyl-l-tyrosine) results in sub-μM binding affinity for the CYP121 enzyme and a complete shift to the high-spin state of the heme FeIII. The introduction of halogens that are able to interact with heme groups is thus a feasible approach to the development of next-generation, tight binding inhibitors of the CYP121 enzyme, in the search for novel antitubercular compounds.
Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors
Giroud, Maude,Dietzel, Uwe,Anselm, Lilli,Banner, David,Kuglstatter, Andreas,Benz, J?rg,Blanc, Jean-Baptiste,Gaufreteau, Delphine,Liu, Haixia,Lin, Xianfeng,Stich, August,Kuhn, Bernd,Schuler, Franz,Kaiser, Marcel,Brun, Reto,Schirmeister, Tanja,Kisker, Caroline,Diederich, Fran?ois,Haap, Wolfgang
, p. 3350 - 3369 (2018/05/01)
Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei (T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors (Ki 50 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys-SOH) during crystallization. The P-glycoprotein efflux ratio was measured and the in vivo brain penetration in rats determined. When tested in vivo in acute HAT model, the compounds permitted up to 16.25 (vs 13.0 for untreated controls) mean days of survival.
LAT-1 activity of meta-substituted phenylalanine and tyrosine analogs
Augustyn, Evan,Finke, Karissa,Zur, Arik A.,Hansen, Logan,Heeren, Nathan,Chien, Huan-Chieh,Lin, Lawrence,Giacomini, Kathleen M.,Colas, Claire,Schlessinger, Avner,Thomas, Allen A.
supporting information, p. 2616 - 2621 (2016/05/09)
The transporter protein Large-neutral Amino Acid Transporter 1 (LAT-1, SLC7A5) is responsible for transporting amino acids such as tyrosine and phenylalanine as well as thyroid hormones, and it has been exploited as a drug delivery mechanism. Recently its role in cancer has become increasingly appreciated, as it has been found to be up-regulated in many different tumor types, and its expression levels have been correlated with prognosis. Substitution at the meta position of aromatic amino acids has been reported to increase affinity for LAT-1; however, the SAR for this position has not previously been explored. Guided by newly refined computational models of the binding site, we hypothesized that groups capable of filling a hydrophobic pocket would increase binding to LAT-1, resulting in improved substrates relative to parent amino acid. Tyrosine and phenylalanine analogs substituted at the meta position with halogens, alkyl and aryl groups were synthesized and tested in cis-inhibition and trans-stimulation cell assays to determine activity. Contrary to our initial hypothesis we found that lipophilicity was correlated with diminished substrate activity and increased inhibition of the transporter. The synthesis and SAR of meta-substituted phenylalanine and tyrosine analogs is described.
Directed hydrogenations and an Ireland-Claisen rearrangement linked to Evans-Tishchenko chemistry: The highly efficient total synthesis of the marine cyclodepsipeptide doliculide
Chen, Tao,Altmann, Karl-Heinz
supporting information, p. 8403 - 8407 (2015/06/02)
Two new convergent total syntheses have been developed for the cytotoxic, actin microfilament-stabilizing marine cyclodepsipeptide doliculide (1). A key strategic element of both routes is the establishment of the central stereogenic center of the characteristic polydeoxypropionate stereotriad by means of a hydroxyl-directed catalytic hydrogenation of a trisubstituted double bond. The requisite olefin substrates were obtained through a modified Suzuki-Miyaura coupling or through Ireland-Claisen rearrangement of a propionate ester, respectively; the latter was the direct result of a highly selective Evans-Tishchenko reduction of a hydroxy ketone that had been obtained in a stereoselective Paterson aldol reaction. Doliculide (1) was finally obtained in a total number of 17 or 15 (14) linear steps, respectively, which represents a substantial improvement over previous syntheses of this highly bioactive natural product.
Total synthesis of mycocyclosin
Cochrane, James R.,White, Jonathan M.,Wille, Uta,Hutton, Craig A.
, p. 2402 - 2405 (2012/06/18)
The first total synthesis of mycocyclosin, a diketopiperazine natural product isolated from M. tuberculosis, is described. While direct oxidative coupling of tyrosine phenolic groups was unsuccessful, construction of the highly strained bicyclic framework was successfully accomplished through an intramolecular Miyaura-Suzuki cross-coupling to generate the biaryl linkage.
