25866-56-2Relevant academic research and scientific papers
Guanidine–Copper Complex Catalyzed Allylic Borylation for the Enantioconvergent Synthesis of Tertiary Cyclic Allylboronates
Ge, Yicen,Cui, Xi-Yang,Tan, Siu Min,Jiang, Huan,Ren, Jingyun,Lee, Nicholas,Lee, Richmond,Tan, Choon-Hong
supporting information, p. 2382 - 2386 (2019/02/01)
An enantioconvergent synthesis of chiral cyclic allylboronates from racemic allylic bromides was achieved by using a guanidine–copper catalyst. The allylboronates were obtained with high γ/α regioselectivities (up to 99:1) and enantioselectivities (up to 99 % ee), and could be further transformed into diverse functionalized allylic compounds without erosion of optical purity. Experimental and DFT mechanistic studies support an SN2′ borylation process catalyzed by a monodentate guanidine–copper(I) complex that proceeds through a special direct enantioconvergent transformation mechanism.
Mechanistic Studies on a Cu-Catalyzed Asymmetric Allylic Alkylation with Cyclic Racemic Starting Materials
Rideau, Emeline,You, Hengzhi,Sidera, Mireia,Claridge, Timothy D. W.,Fletcher, Stephen P.
supporting information, p. 5614 - 5624 (2017/04/27)
Mechanistic studies on Cu-catalyzed asymmetric additions of alkylzirconocene nucleophiles to racemic allylic halide electrophiles were conducted using a combination of isotopic labeling, NMR spectroscopy, kinetic modeling, structure-activity relationships, and new reaction development. Kinetic and dynamic NMR spectroscopic studies provided insight into the oligomeric Cu-ligand complexes, which evolve during the course of the reaction to become faster and more highly enantioselective. The Cu-counterions play a role in both selecting different pathways and in racemizing the starting material via formation of an allyl iodide intermediate. We quantify the rate of Cu-catalyzed allyl iodide isomerization and identify a series of conditions under which the formation and racemization of the allyl iodide occurs. We developed reaction conditions where racemic allylic phosphates are suitable substrates using new phosphoramidite ligand D. D also allows highly enantioselective addition to racemic seven-membered-ring allyl chlorides for the first time.1H and2H NMR spectroscopy experiments on reactions using allylic phosphates showed the importance of allyl chloride intermediates, which form either by the action of TMSCl or from an adventitious chloride source. Overall these studies support a mechanism where complex oligomeric catalysts both racemize the starting material and select one enantiomer for a highly enantioselective reaction. It is anticipated that this work will enable extension of copper-catalyzed asymmetric reactions and provide understanding on how to develop dynamic kinetic asymmetric transformations more broadly.
Development of Noviomimetics as C-Terminal Hsp90 Inhibitors
Anyika, Mercy,McMullen, Mason,Forsberg, Leah K.,Dobrowsky, Rick T.,Blagg, Brian S. J.
supporting information, p. 67 - 71 (2016/02/03)
KU-32 and KU-596 are novobiocin-derived, C-terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.
Engineering an antibiotic to fight cancer: Optimization of the novobiocin scaffold to produce anti-proliferative agents
Zhao, Huiping,Donnelly, Alison C.,Kusuma, Bhaskar R.,Brandt, Gary E. L.,Brown, Douglas,Rajewski, Roger A.,Vielhauer, George,Holzbeierlein, Jeffrey,Cohen, Mark S.,Blagg, Brian S. J.
scheme or table, p. 3839 - 3853 (2011/09/13)
Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ?700- fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization of structure- activity relationships established for three novobiocin synthons produced optimized scaffolds, which manifest midnanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition.
Enzymatic resolution of racemic secondary cyclic allylic alcohols
Winska, Katarzyna,Grudniewska, Aleksandra,Chojnacka, Anna,Bialonska, Agata,Wawrzenczyk, Czeslaw
experimental part, p. 670 - 678 (2010/08/07)
The resolutions of five racemic cyclic alcohols: 6,6-dimethylcyclohex-2-en-1-ol (±)-5, 4,4-dimethylcyclohex-2-en-1-ol (±)-7, 5,5-dimethylcyclohex-2-en-1-ol (±)-11 and isomeric trans-(±)-13 and cis-piperitols (±)-14 are presented. They were resolved by enzymatic esterification with vinyl esters or by enzymatic hydrolysis of their racemic esters in phosphate buffer. The following lipases were used as biocatalysts: Novozyme 435 (Candida antarctica), Amano PS (Burkholderia cepacia) and lipase from Candida cylindracea. All isomers of alcohols were obtained with at least 96% ee.
A study of Heck cyclization reactions to form phenanthridine ring systems
Donaldson, Lauren R.,Haigh, David,Hulme, Alison N.
, p. 4468 - 4477 (2008/09/20)
A survey of conditions for the palladium catalyzed intramolecular Heck cyclization of protected amines has shown that the Herrmann-Beller palladacycle can be exploited under 'cationic' conditions to provide a robust and rapid route (2 h) to the synthesis
Transmission of Substituent Effects through Unsaturated Systems. Part 6. Kinetics of Reduction of β-Substituted α, β-Unsaturated Ketones with Sodium Borohydride
Geribaldi, Serge,Decouzon, Michele,Boyer, Bernard,Moreau, Claude
, p. 1327 - 1330 (2007/10/02)
The rate constants for addition of sodium borohydride to 3-substituted 5,5-dimethylcyclohex-2-enones (1), para-substituted 3-phenylcyclohexenones (2), and para-substituted acetophenones (3) have been determined in an alkaline solution (NaOH, 0.025 mol l-1) of water-dioxane (1:1 v/v) at 298 K.The conjugated cyclohexenone systems (1) and (2) undergo exclusive 1,2-reduction in these conditions to produce the corresponding allylic alcohols.The regioselectivity of reduction is discussed.The linear free energy relationships obtained between the rate constants and ?p or ?p+ confirm that these 3-substituted cyclohexenone structures are good models for the investigation of the substituent effects on the reactivity of ethylenic systems.Comparison of reaction constants for the three series leads to the conclusion that, as for borohydride reductions of acetophenone, the cyclohexenone reduction must have a late transition state in the final quarter of the reaction co-ordinate.
Insect Growth Regulators. XVI Syntheses of Juvenoids with the 3,3-Dimethylcyclohexane System.
Wawrzenczyk, Czeslaw,Lochynski, Stanislaw
, p. 99 - 110 (2007/10/02)
New cyclic juvenoids containing the 3,3-dimethylcyclohexane (esters 16, 18, 22, 26, and ehters 28a,b) or the 5,5-dimethyl-2-cyclohexene system (esters 15, 17, 21, 25, and ehters 27a,b) have been obtained by a several-step synthesis starting from dimedone (1).The compounds obtained exhibited morphogenetic activity against larvae of Dysdercus cingulatus and they were inactive on pupae of Tenebrio molitor.Keywords: Claisen rearrangement; gem-Dimethylcyclohexane derivatives; Juvenoids
THE INFLUENCE OF LITHIUM COMPLEXING AGENTS ON THE REGIOSELECTIVITY OF REDUCTIONS OF SUBSTITUTED 2-CYCLOHEXENONES BY LiAlH4 and LiBH4
Loupy, Andre,Seyden-Penne, Jacqueline
, p. 1937 - 1942 (2007/10/02)
A reversal of regioselectivity of LiAlH4 or LiBH4 reduction of 2-cyclohexenone induced by addition of -cryptand to the reaction medium is accompanied by a rate decrease.In the absence of the cryptand, carbonyl attack predominates (C1:C3=86:14 with LiAlH4 in THF).In the presence of the cryptand, double bond attack is favoured (C1:C3=14:86).This effect is larger with LiAlH4 than with LiBH4.This trend is general in the case of five substituted 2-cyclohexenones.Using 12-crown-4 as a Li+ coordinator, a change in regioselectivity occurs but it is less pronunced than with the cryptand.
