- Catalysis of the Hajos-Parrish-Eder-Sauer-Wiechert reaction by cis- and trans-4,5-methanoprolines: Sensitivity of proline catalysis to pyrrolidine ring conformation
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Methanoprolines are found to be catalysts for the Hajos-Parrish-Eder-Sauer- Wiechert reaction.[1] cis-4,5-Methanoproline exhibits catalytic ability similar to proline (86% yield, 93% ee), whereas the trans-4,5- methanoproline is less selective (67% yield, 83% ee) and shows less acceleration. The reaction was also studied with hybrid density functional theory (B3LYP). The nearly planar cis-4,5-methanoproline amine better reflects the planar iminium of the transition states than the pyramidalized trans4,5-methanoproline. This difference in conformation is responsible for the observed higher enantioselectivity and enhanced catalytic behavior of the cis-4,5-methanoproline.
- Cheong, Paul Ha-Yeon,Houk,Warrier, Jayakumar S.,Hanessian, Stephen
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- Construction of key building blocks towards the synthesis of cortistatins
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This work reports the construction of key building blocks towards the synthesis of cortistatins; a family of steroidal alkaloids. Cortistatin A, being a primary target due to its superior biological properties over other congeners, has been prepared by two different synthetic routes. Synthesis of the precursor to the heavily substituted A-ring starting from d-glucose and construction of the DE-ring junction employing a Hajos-Parrish ketone as a chiral pool have been demonstrated. Efforts are underway to assemble these key fragments and build towards the total synthesis of cortistatin A.
- Indu, Satrajit,Kaliappan, Krishna P.,Telore, Rahul D.
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supporting information
p. 2432 - 2446
(2020/04/22)
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- Bifunctional organocatalysts based on a carbazole scaffold for the synthesis of the Hajos-Wiechert and Wieland-Miescher ketones
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Several bifunctional organocatalysts based on a carbazole scaffold containing a chiral amine and a synthetic oxyanion-hole have been synthesized and successfully applied to the synthesis of the Hajos-Wiechert and Wieland-Miescher ketones (up to 99% ee). Both enamine activation and H-bonding donor ability of these catalysts were evaluated by preparing catalysts differing in the nature of the amine [(R,R)-cyclohexanediamine or l-proline], the H-bond donor functional group (sulfonamide or amide) and the number of NH bonds. Modeling studies and an X-ray structure fully support the obtained results.
- Rubio, Omayra H.,Fuentes De Arriba, ángel L.,Monleón, Laura M.,Sanz, Francisca,Simón, Luis,Alcázar, Victoria,Morán, Joaquín R.
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supporting information
p. 1297 - 1303
(2015/03/05)
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- Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward Astellatol and the Total Synthesis of (-)-Nitidasin
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Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans-hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems, posing significant challenges for chemical synthesis. Herein, the evolution of our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids is detailed. These endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second-generation and a third-generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (-)-nitidasin. In particular, a series of substrate-controlled transformations to install the ten stereogenic centers of the target molecule was orchestrated and the carbocyclic backbone was forged in a convergent fashion. Furthermore, the progress toward the synthesis of astellatol is disclosed and insights into some observed yet unexpected diastereoselectivities by detailed quantum-mechanical calculations are provided. Two and a half molecules: Astellatol and nitidasin are polycyclic sesterterpenoids, posing considerable challenges for synthetic chemists. In this full account, the evolution of a synthetic strategy for these and structurally related natural products is given (see scheme). The presented work includes efforts toward a biomimetic synthesis of astellatol, a successful route for the first total synthesis of (-)-nitidasin, and quantum-mechanical investigations into unexpected diastereosectivities.
- Hog, Daniel T.,Huber, Florian M. E.,Jiménez-Osés, Gonzalo,Mayer, Peter,Houk, Kendall N.,Trauner, Dirk
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supporting information
p. 13646 - 13665
(2015/09/22)
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- Novel supported and unsupported prolinamides as organocatalysts for enantioselective cyclization of triketones
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A novel prolylsulfonamide derived from ethylene diamine and its supported counterpart has been prepared and tested as enantioselective intramolecular aldol reaction of cyclic and acyclic triketones. Good to excellent yields and enantioselectivities have been obtained in water and under solvent free conditions.
- Pedrosa, Rafael,Andrés, José María,Manzano, Rubén,Pérez-López, César
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supporting information
p. 3101 - 3104
(2013/06/27)
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- The A-CD analogue of 16β,17α-estriol is a potent and highly selective estrogen receptor β agonist
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Selective estrogen receptor β (ERβ) agonists display neuroprotective properties in animal models and hold promise in the treatment of neurodegenerative diseases. In our quest to design, synthesize and evaluate potent and safe ERβ agonists, we focused on m
- Sauvee, Claire,Schaefer, Anja,Sunden, Henrik,Ma, Jian-Nong,Gustavsson, Anna-Lena,Burstein, Ethan S.,Olsson, Roger
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supporting information
p. 1439 - 1442
(2013/11/19)
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- A-CD estrogens. I. substituent effects, hormone potency, and receptor subtype selectivity in a new family of flexible estrogenic compounds
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Long-term use of estrogen supplements by women leads to an increased risk of breast and uterine cancers. Possible mechanisms include metabolism of estradiol and compounds related to tumor-initiating quinones, and ligand-induced activation of the estrogen receptors ERα and ERβ which can cause cancer cell proliferation, depending on the ratio of receptors present. One therapeutic goal would be to create a spectrum of compounds of variable potency for ERα and ERβ, which are resistant to quinone formation, and to determine an optimum point in this spectrum. We describe the synthesis, modeling, binding affinities, hormone potency, and a measure of quinone formation for a new family of A-CD estrogens, where the A-C bond is formed by ring coupling. Some substituents on the A-ring increase hormone potency, and one compound is much less quinone-forming than estradiol. These compounds span a wide range of receptor subtype selectivities and may be useful in hormone replacement therapy.
- Wright, James S.,Shadnia, Hooman,Anderson, James M.,Durst, Tony,Asim, Muhammad,El-Salfiti, Mohamed,Choueiri, Christine,Pratt, M. A. Christine,Ruddy, Samantha C.,Lau, Rosanna,Carlson, Kathryn E.,Katzenellenbogen, John A.,Obrien, Peter J.,Wan, Luke
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scheme or table
p. 433 - 448
(2011/04/15)
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- Proline imidazolidinones and enamines in Hajos-Wiechert and Wieland-Miescher ketone synthesis
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Readily available aromatic prolinamides obtained from the acid chloride of proline hydrochloride and anilines induce large enantiomeric excesses in intramolecular aldol condensations. Imidazolidinones derived from the reaction of the catalyst and enamines
- de Arriba, ángel L. Fuentes,Simón, Luis,Raposo, César,Alcázar, Victoria,Morán, Joaquín R.
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body text
p. 4841 - 4845
(2009/10/02)
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- Evaluating β-amino acids as enantioselective organocatalysts of the Hajos-Parrish-Eder-Sauer-Wiechert reaction
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A systematic study of the effect of substitution within the β-amino acid framework indicates that both β2- and β3- amino acids catalyse the Hajos-Parrish-Eder-Sauer-Wiechert reaction with poor to reasonable levels of enantioselectivity. These results led to the evaluation of the conformationally constrained β-amino acid (1R,2S)-cispentacin, which catalyses the Hajos-Parrish-Eder-Sauer-Wiechert reaction with comparable or higher levels of enantioselectivity to l-proline. The Royal Society of Chemistry.
- Davies, Stephen G.,Russell, Angela J.,Sheppard, Ruth L.,Smith, Andrew D.,Thomson, James E.
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p. 3190 - 3200
(2008/03/14)
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- Asymmetric one-pot Robinson annulations
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One-pot syntheses of ketol SS-5a, enone S-2 and optically active spiroenediones S-14, R-7 and S-15 are reported.
- Rajagopal,Narayanan,Swaminathan
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p. 4887 - 4890
(2007/10/03)
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- Proline mediated asymmetric ketol cyclization: A template reaction
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1H, 13C and ATR-FTIR Spectroscopic studies reveal that the asymmetric cyclization of prochiral triones 1 and 2 in the presence of S-proline is a template reaction.
- Rajagopal,Moni,Subramanian,Swaminathan
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p. 1631 - 1634
(2007/10/03)
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- Use of Winterfeldt's template to control the C-2' configuration in the synthesis of strigol-type compounds
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A route comprising (i) a cycloaddition reaction of citraconic anhydride with the Winterfeldt auxiliary, (ii) hydride reduction of the cycloadduct, (iii) a (formal) ether formation, and (iv) a cycloreversion reaction allows efficient stereocontrol at C-2' in the synthesis of strigol and its structural analogues.
- Roehrig, Susanne,Hennig, Lothar,Findeisen, Matthias,Welzel, Peter,Mueller, Dietrich
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p. 3439 - 3456
(2007/10/03)
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- Asymmetric Michael addition of malonate anions to prochiral acceptors catalyzed by L-proline rubidium salt
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L-Proline rubidium salt catalyzes the asymmetric Michael addition of malonate anions to prochiral enones and enals. This method can be applied to a wide range of substrates to give adducts with a predictable absolute configuration: (S)-adducts from (E)-enones/enals and (R)-adducts from cyclic (Z)-enones. Both the secondary amine moiety and the carboxylate moiety are critical for the catalytic activity and asymmetric induction. Varying the countercation also affects the reaction course. High enantiomeric excesses were attained when di(tert-butyl) malonate was added to (E)-enones in the presence of CsF. The stereochemistry of the Michael reaction indicates that asymmetric induction takes place via enantioface discrimination involving the acceptor α-carbon atom rather than the β-carbon atom.
- Yamaguchi, Masahiko,Shiraishi, Tai,Hirama, Masahiro
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p. 3520 - 3530
(2007/10/03)
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- Nonlinear Effects in Asymmetric Synthesis. Examples in Asymmetric Oxidations and Aldolization Reactions
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It has been shown in three experiments that there is a strong departure from the linear relationship usually assumed between the enantiomeric excess of a chiral auxiliary and the extent of the asymmetric synthesis.This gives useful information on the reac
- Puchot, C.,Samuel, O.,Dunach, E.,Zhao, S.,Agami, C.,Kagan, H. B.
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p. 2353 - 2357
(2007/10/02)
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- Asymmetric synthesis of organic compounds
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Optically active organic compounds are prepared starting from optically inactive reactants by means of an optically active agent which influences the course of the reaction. In particular optically active compounds having a "meso" type carbon atom undergo an intramolecular ring closure in the presence of an optically active agent to yield an optically active product having one additional ring. The present process is particularly useful in the preparation of optically active bicyclic diketones which are important intermediates in the total synthesis of steroids.
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