61362-77-4Relevant articles and documents
Total Synthesis of Amphirionin-4
Holmes, Michael,Kwon, Daniel,Taron, Matthew,Britton, Robert
, p. 3868 - 3871 (2015)
The first total synthesis of amphirionin-4 has been achieved using a combination of cross-coupling strategies to access the polyene side chain and a chlorohydrin-based approach to construct the tetrahydrofuranol core. The remote C9-stereocenter was introd
Toward an analogue of the transition state of preD3-D3 isomerization: Stereoselective synthesis of linearly fused 6-8-6 carbocyclic systems
Codesido, Eva M.,Rodriguez, J. Ramon,Castedo, Luis,Granja, Juan R.
, p. 1651 - 1654 (2002)
Matrix presented A stereoselective synthesis of 6-8-6 fused carbocyclic systems based on enol alkylation, ketone allylation, RCM, and Heck cyclization was developed to obtain compounds with a carbon framework that mimics the putative transition structure of the isomerization of previtamin D3 to vitamin D3.
Mechanism-based inactivation by aromatization of the transaminase BioA involved in biotin biosynthesis in mycobaterium tuberculosis
Shi, Ce,Geders, Todd W.,Park, Sae Woong,Wilson, Daniel J.,Boshoff, Helena I.,Abayomi, Orishadipe,Barry, Clifton E.,Schnappinger, Dirk,Finzel, Barry C.,Aldrich, Courtney C.
, p. 18194 - 18201 (2011)
BioA catalyzes the second step of biotin biosynthesis, and this enzyme represents a potential target to develop new antitubercular agents. Herein we report the design, synthesis, and biochemical characterization of a mechanism-based inhibitor (1) featuring a 3,6-dihydropyrid-2-one heterocycle that covalently modifies the pyridoxal 5′-phosphate (PLP) cofactor of BioA through aromatization. The structure of the PLP adduct was confirmed by MS/MS and X-ray crystallography at 1.94 A resolution. Inactivation of BioA by 1 was time- and concentration-dependent and protected by substrate. We used a conditional knock-down mutant of M. tuberculosis to demonstrate the antitubercular activity of 1 correlated with BioA expression, and these results provide support for the designed mechanism of action.
Synthesis of a Human Urinary Metabolite of Prostaglandin D2
Kimbrough, Jennifer R.,Austin, Zachary,Milne, Ginger L.,Sulikowski, Gary A.
, p. 10048 - 10051 (2019)
A chemical synthesis of the major human metabolite of prostaglandin D2, tricyclic-PGDM, is described. The synthetic route starts from iodocyclopentenone 1 (available from cyclopentadiene in 6 steps) and requires 13 synthetic transformations. The synthetic route takes advantage of a contrasteric allylation to establish the 1,2-cis relationship between the ring hydroxyl group and side chain. A second key sequence is the application of Fu's copper-catalyzed C-H insertion of a diazoacetate followed by an alkyne semihydrogenation to introduce the unsaturated side chain.
Alkyne Aminopalladation/Heck and Suzuki Cascades: An Approach to Tetrasubstituted Enamines
Geffers, Finn J.,Jones, Peter G.,Kurth, Florens R.,Werz, Daniel B.
supporting information, p. 14846 - 14850 (2021/10/19)
Alkyne aminopalladation reactions starting from tosylamides are reported. The emerging vinylic Pd species are converted either in an intramolecular Heck reaction with olefinic units or in an intermolecular Suzuki reaction by using boronic acids exhibiting broad functional group tolerance. Tetra(hetero)substituted tosylated enamines are obtained in a simple one-pot process.
Copper-Catalyzed Perfluoroalkylation of Alkynyl Bromides and Terminal Alkynes
Fan, Shilu,Zheng, Chenggong,Zheng, Kaiting,Li, Junlan,Liu, Yaomei,Yan, Fangpei,Xiao, Hua,Feng, Yi-Si,Zhu, Yuan-Yuan
supporting information, p. 3190 - 3194 (2021/05/05)
A copper-catalyzed one-pot perfluoroalkylation of alkynyl bromides and terminal alkynes has been disclosed, and the corresponding perfluoroalkylated alkynes could be attained in good to excellent yields. The new straightforward transformation shows high efficiency (0.01-0.5 mol % catalyst loading), broad substrate scope, and remarkable functional group tolerance and provides a facile approach for useful application in life and material sciences.
Targeting a Novel KRAS Binding Site: Application of One-Component Stapling of Small (5-6-mer) Peptides
Carbajo, Rodrigo J.,Dou, Rongxuan,Fumagalli, Gabriele,Nissink, J. Willem M.,Spring, David R.,Tart, Jonathan,Thomas, Andrew P.
supporting information, p. 17287 - 17303 (2021/12/02)
RAS proteins are central in the proliferation of many types of cancer, but a general approach toward the identification of pan-mutant RAS inhibitors has remained unresolved. In this work, we describe the application of a binding pharmacophore identified from analysis of known RAS binding peptides to the design of novel peptides. Using a chemically divergent approach, we generated a library of small stapled peptides from which we identified compounds with weak binding activity. Exploration of structure-activity relationships (SARs) and optimization of these early compounds led to low-micromolar binders of KRAS that block nucleotide exchange.
Structurally Diverse Acyl Bicyclobutanes: Valuable Strained Electrophiles
Attard, Riley H.,Gardiner, Michael G.,Malins, Lara R.,Schwartz, Brett D.,Zhang, Meng Yao
supporting information, p. 2808 - 2812 (2020/03/04)
Bicyclo[1.1.0]butanes (BCBs) are highly strained carbocycles that have emerged as versatile synthetic tools, particularly for the construction of functionalized small molecules. This work reports two efficient pathways for the rapid preparation of over 20 structurally diverse BCB ketones, encompassing simple alkyl and aryl derivatives, as well as unprecedented amino acid, dipeptide, bioisostere, and bifunctional linchpin reagents currently inaccessible using literature methods. Analogues are readily forged in two steps and in high yields from simple carboxylic acids or through unsymmetrical ketone synthesis beginning with a convenient carbonyl dication equivalent. The utility of this novel toolbox of strained electrophiles for the selective modification of proteinogenic nucleophiles is highlighted.
Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines
Lu, Benjamin L.,Williams, Geoffrey M.,Verdon, Daniel J.,Dunbar, P. Rod,Brimble, Margaret A.
supporting information, p. 2282 - 2291 (2019/10/02)
Cancer immunotherapy has gained increasing attention due to its potential specificity and lack of adverse side effects when compared to more traditional modes of treatment. Toll-like receptor 2 (TLR2) agonists are lipopeptides possessing the S-[2,3-bis(palmitoyloxy)propyl]-l-cysteine (Pam2Cys) motif and exhibit potent immunostimulatory effects. These agonists offer a means of providing "danger signals" in order to activate the immune system toward tumor antigens. Thus, the development of TLR2 agonists is attractive in the search of potential immunostimulants for cancer. Existing SAR studies of Pam2Cys with TLR2 indicate that the structural requirements for activity are, for the most part, very intolerable. We have investigated the importance of stereochemistry, the effect of N-terminal acylation, and homologation between the two ester functionalities in Pam2Cys-conjugated lipopeptides on TLR2 activity. The R diastereomer is significantly more potent than the S diastereomer and N-terminal modification generally lowers TLR2 activity. Most notably, homologation gives rise to analogues which are comparatively active to the native Pam2Cys containing constructs.
Gold(I)/Gold(III) Catalysis that Merges Oxidative Addition and π-Alkene Activation
Amgoune, Abderrahmane,Bourissou, Didier,Rigoulet, Mathilde,Thillaye du Boullay, Olivier
supporting information, p. 16625 - 16630 (2020/07/24)
Heteroarylation of alkenes with aryl iodides was efficiently achieved with a (MeDalphos)AuCl complex through AuI/AuIII catalysis. The possibility to combine oxidative addition of aryl iodides and π-activation of alkenes at gold is demonstrated for the first time. The reaction is robust and general (>30 examples including internal alkenes, 5-, 6-, and 7-membered rings). It is regioselective and leads exclusively to trans addition products. The (P,N) gold complex is most efficient with electron-rich aryl substrates, which are troublesome with alternative photoredox/oxidative approaches. In addition, it provides a very unusual switch in regioselectivity from 5-exo to 6-endo cyclization between the Z and E isomers of internal alkenols.
