- Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure-Activity Relationship, Inhibition Mechanism, Metabolism, and in Vivo Studies
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Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorable metabolism and biodistribution by accumulation in mice brain tissue after intraperitoneal and oral administration. The highest antitrypanosomal activity was observed for inhibitors with an N-terminal 2,3-dihydrobenzo[b][1,4]dioxine group and a 4-Me-Phe residue in P2 (2e/4e) with nanomolar EC50 values (0.14/0.80 μM). The different mechanisms of reversible and irreversible inhibitors were explained using QM/MM calculations and MD simulations.
- Jung, Sascha,Fuchs, Natalie,Johe, Patrick,Wagner, Annika,Diehl, Erika,Yuliani, Tri,Zimmer, Collin,Barthels, Fabian,Zimmermann, Robert A.,Klein, Philipp,Waigel, Waldemar,Meyr, Jessica,Opatz, Till,Tenzer, Stefan,Distler, Ute,R?der, Hans-Joachim,Kersten, Christian,Engels, Bernd,Hellmich, Ute A.,Klein, Jochen,Schirmeister, Tanja
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p. 12322 - 12358
(2021/09/02)
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- Generation of potent Nrf2 activators via tuning the electrophilicity and steric hindrance of vinyl sulfones for neuroprotection
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Oxidative stress is constantly involved in the etiopathogenesis of an ever-widening range of neurodegenerative diseases. As a consequence, effective repression of cellular oxidative stress to a redox homeostatic condition is a promising and feasible strategy to treat, or at least retard the progression of, such disorders. Nrf2, a primary orchestrator of cellular antioxidant response machine, is responsible for detoxifying and compensating for deleterious oxidative stress via transcriptional activation of a diverse array of antioxidant biomolecules. In the framework of our persistent interest in disclosing small molecules that interfere with cellular redox-regulating machinery, we report herein the synthesis, optimization, and biological assessment of 47 vinyl sulfone scaffold-bearing small molecules, most of which exhibit robust neuroprotective effect against H2O2-mediated lesions to PC12 cells. After initial screening, the most potent neuroprotective compounds 9b and 9c with marginal cytotoxicity were selected for the follow-up studies. Our results demonstrate that their neuroprotective effects are attributed to the up-regulation of a panel of antioxidant genes and corresponding gene products. Further mechanistic studies indicate that Nrf2 is indispensable for the cellular performances of 9b and 9c, arising from the fact that silence of Nrf2 gene drastically nullifies their protective action. Taken together, 9b and 9c discovered in this work merit further development as neuroprotective candidates for the treatment of oxidative stress-mediated pathological conditions.
- Song, Zi-Long,Hou, Yanan,Bai, Feifei,Fang, Jianguo
-
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- Isomerisation of Vinyl Sulfones for the Stereoselective Synthesis of Vinyl Azides
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Reported is the construction, and facile base-mediated conversation of ten differently substituted 3-azido E-vinyl sulfones (γ-azido-α,β-unsaturated sulfones) into their isomeric vinyl azide counterparts. The requisite 3-azido E-vinyl sulfones were prepared from 3-bromo E-vinyl sulfones, which in turn were accessed from allyl sulfones via a bromination-elimination sequence. In relation to this a one-pot azidation-isomerisation sequence was developed which enabled the direct formation of the vinyl azides from the corresponding 3-bromo E-vinyl sulfones. Similarly, a convenient one-pot Horner–Wadsworth–Emmons olefination-isomerisation approach was utilised in order to prepare some of the allylic sulfones used in this study. The vinyl azide forming process typically proceeded with high levels of Z-selectivity, although this was dependent on the vinyl sulfone substitution pattern. Thus, with either no substituent or a methyl group in the γ- or β-position, relative to the sulfone, good, to high levels of Z-selectivity (Z/E = 85:15 to ≥ 95:5) were obtained. However, incorporation of an α-sulfonyl methyl substituent led to an E-selective process (Z/E = 20:80). A non-bonding interaction between the azido group and the α-sulfonyl vinylic proton is proposed, which acts as a conformational control mechanism to help guide the stereochemical outcome.
- Collins, Niall,Connon, Robert,Evans, Paul,Sánchez-Sanz, Goar
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p. 6228 - 6235
(2020/10/02)
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- Selective caspase inhibitors and uses thereof
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The present invention relates to compounds of Formula I, IA, II, HA, III, or IHA and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more caspases. Also described are methods where the compounds of Formula I, IA, II, IIA, III, or IIIA are used in the prevention and/or treatment of various diseases and conditions in subjects, including caspase-mediated diseases such as sepsis, myocardial infarction, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative disease (e.g. multiple sclerosis (MS) and Alzheimer's, Parkinson's, and Huntington's diseases).
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Page/Page column 102
(2017/02/28)
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- Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors
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We propose a structure-based protocol for the development of customized covalent inhibitors. Starting from a known inhibitor, in the first and second steps appropriate substituents of the warhead are selected on the basis of quantum mechanical (QM) computations and hybrid approaches combining QM with molecular mechanics (QM/MM). In the third step the recognition unit is optimized using docking approaches for the noncovalent complex. These predictions are finally verified by QM/MM or molecular dynamic simulations. The applicability of our approach is successfully demonstrated by the design of reversible covalent vinylsulfone-based inhibitors for rhodesain. The examples show that our approach is sufficiently accurate to identify compounds with the desired properties but also to exclude nonpromising ones.
- Schirmeister, Tanja,Kesselring, Jochen,Jung, Sascha,Schneider, Thomas H.,Weickert, Anastasia,Becker, Johannes,Lee, Wook,Bamberger, Denise,Wich, Peter R.,Distler, Ute,Tenzer, Stefan,Johé, Patrick,Hellmich, Ute A.,Engels, Bernd
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supporting information
p. 8332 - 8335
(2016/07/26)
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- Photoredox α-vinylation of α-amino acids and N -aryl amines
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A new coupling protocol has been developed that allows the union of vinyl sulfones with photoredox-generated α-amino radicals to provide allylic amines of broad diversity. Direct C-H vinylations of N-aryl tertiary amines, as well as decarboxylative vinylations of N-Boc α-amino acids, proceed in high yield and with excellent olefin geometry control. The utility of this new allyl amine forming reaction has been demonstrated via the syntheses of several natural products and a number of established pharmacophores.
- Noble, Adam,MacMillan, David W. C.
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supporting information
p. 11602 - 11605
(2014/11/08)
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- Discovery of vinyl sulfones as a novel class of neuroprotective agents toward Parkinson's disease therapy
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Although the etiology of Parkinson's disease (PD) remains elusive, recent studies suggest that oxidative stress contributes to the cascade leading to dopaminergic (DAergic) neurodegeneration. The Nrf2 signaling is the main pathway responsible for cellular defense system against oxidative stress. Nrf2 is a transcription factor that regulates environmental stress response by inducing expression of antioxidant enzyme genes. We have synthesized novel vinyl sulfone derivatives. They exhibited a broad range of activities in inducing HO-1, whose gene expression is under the control of Nrf2. Among them, compound 12g was confirmed to activate Nrf2 and induce expression of the Nrf2-dependent antioxidant enzymes NQO1, GCLC, GLCM, and HO-1, at both mRNA and protein levels in DAergic neuronal cells. This was accompanied by protection of DAergic neurons in both in vitro and MPTP-induced in vivo models of PD. In addition, compound 12g effectively resulted in attenuation of the PD-associated behavioral deficits in the mouse model.
- Woo, Seo Yeon,Kim, Ji Hyun,Moon, Mi Kyeong,Han, Se-Hee,Yeon, Seul Ki,Choi, Ji Won,Jang, Bo Ko,Song, Hyo Jung,Kang, Yong Gu,Kim, Jin Woo,Lee, Jaeick,Kim, Dong Jin,Hwang, Onyou,Park, Ki Duk
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supporting information
p. 1473 - 1487
(2014/03/21)
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- Vinyl sulfone-based peptidomimetics as anti-trypanosomal agents: Design, synthesis, biological and computational evaluation
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A series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against Trypanosoma brucei brucei. These electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through alkylation of a key cysteine residue within the protease active site. The series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to a range of substitutions at the P1, P1′, and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole cell assay), displayed minimal toxicity (>785 times selectivity) when assayed for cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells treated with compound 29, as with K777 (2), exhibited an increase in both the number of multinucleated cells and cells with swollen flagellar pockets. Computational analysis revealed a strong correlation between the hypothetical binding mode in TbCatB/rhodesain and trypanocidal activity in vitro.
- Dunny, Elizabeth,Doherty, William,Evans, Paul,Malthouse, J. Paul G.,Nolan, Derek,Knox, Andrew J.S.
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p. 6638 - 6650
(2013/10/01)
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- Chemical introduction of the green fluorescence: Imaging of cysteine cathepsins by an irreversibly locked GFP fluorophore
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An activity-based probe, containing an irreversibly locked GFP-like fluorophore, was synthesized and evaluated as an inhibitor of human cathepsins and, as exemplified with cathepsin K, it proved to be suitable for ex vivo imaging and quantification of cysteine cathepsins by SDS-PAGE.
- Frizler, Maxim,Yampolsky, Ilia V.,Baranov, Mikhail S.,Stirnberg, Marit,Gütschow, Michael
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p. 5913 - 5921
(2013/09/12)
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- Proteomic profiling and potential cellular target identification of K11777, a clinical cysteine protease inhibitor, in Trypanosoma brucei
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We report herein the design, synthesis and application of K11777-derived activity-based probes (ABPs) allowing in situ profiling and identification of potential cellular targets of K11777 in Trypanosoma brucei.
- Yang, Peng-Yu,Wang, Min,He, Cynthia Y.,Yao, Shao Q.
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p. 835 - 837
(2012/02/05)
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- Rh2(II)-catalyzed nitro-group migration reactions: Selective synthesis of 3-nitroindoles from β-nitro styryl azides
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Rhodium carboxylate complexes (1 mol %) catalyze the migration of electron-withdrawing groups to selectively produce 3-substituted indoles from β-substituted styryl azides. The relative order of migratorial aptitude for this transformation is ester ? amide H sulfonyl benzoyl ? nitro.
- Stokes, Benjamin J.,Liu, Sheng,Driver, Tom G.
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supporting information; experimental part
p. 4702 - 4705
(2011/05/16)
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- Organocatalyst-mediated enantioselective intramolecular Michael addition of aldehydes to vinyl sulfones
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Chiral amines with a hydrogen bond donor promote the intramolecular conjugate addition of aldehydes to vinyl sulfones. Chiral cyclic sulfone-aldehydes are obtained in good yields with an ee of up to 82%.
- Bournaud, Chloee,Marchal, Estelle,Quintard, Adrien,Sulzer-Mosse, Sarah,Alexakis, Alexandre
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experimental part
p. 1666 - 1673
(2010/10/04)
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- Stereocontrolled synthesis of trans-cyclopropyl sulfones from terminal epoxides
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(Figure presented) Treatment of a range of (enantiopure) epoxides with the sodium salt of diethyl (phenylsulfonyl)methylphosphonate in DME at 140 °C for 4 h gives a variety of (enantiopure) trans-cyclopropyl sulfones with high diastereoselectivity.
- Bray, Christopher D.,De Faveri, Giorgio
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supporting information; experimental part
p. 4652 - 4655
(2010/09/14)
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- Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition
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A series of artemisinin-vinyl sulfone hybrid molecules with the potential to act in the parasite food vacuole via endoperoxide activation and falcipain inhibition was synthesized and screened for antiplasmodial activity and falcipain-2 inhibition. All conjugates were active against the Plasmodium falciparum W2 strain in the low nanomolar range and those containing the Leu-hPhe core inhibited falcipain-2 in low micromolar range.
- Capela, Rita,Oliveira, Rudi,Goncalves, Lidia M.,Domingos, Ana,Gut, Jiri,Rosenthal, Philip J.,Lopes, Francisca,Moreira, Rui
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body text
p. 3229 - 3232
(2010/05/02)
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- Dipeptidyl α-fluorovinyl Michael acceptors: Synthesis and activity against cysteine proteases
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The synthesis of novel dipeptidyl α-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8ΔCTE) revealed low biological activity. Relative rates of Michael additions of 2′-(phenethyl)thiol with vinyl sulfone and α-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.
- Steert, Koen,El-Sayed, Ibrahim,Van der Veken, Pieter,Krishtal, Alisa,Van Alsenoy, Christian,Westrop, Gareth D.,Mottram, Jeremy C.,Coombs, Graham H.,Augustyns, Koen,Haemers, Achiel
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p. 6563 - 6566
(2008/03/14)
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- Synthesis of the multisubstituted halogenated olefins via cross-coupling of dihaloalkenes with alkylzinc bromides
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The 1-fluoro-1-haloalkenes undergo Pd-catalyzed Negishi cross-couplings with primary alkylzinc bromides to give multisubstituted fluoroalkenes. The alkylation was trans-selective giving pure Z-fluoroalkenes in most cases. The highest yields were obtained with Pd2(dba)3 and PdCl 2(dppb) catalysts but the best stereochemical outcome was obtained with less reactive Pd(PPh3)4. The tertiary alkylzincs also produced desired fluoroalkenes in high yields. Coupling of β,β- dichlorostyrene with organozinc reagent resulted in the formation of monocoupled product.
- Andrei, Daniela,Wnuk, Stanislaw F.
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p. 405 - 408
(2007/10/03)
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- Peptidyl allyl sulfones
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The present disclosure provides compositions for inhibiting proteases, methods for synthesizing the compositions, and methods of using the disclosed protease inhibitors. Aspects of the disclosure include peptidyl allyl sulfone compositions that inhibit proteases, for example cysteine proteases, either in vivo or in vitro.
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Page/Page column 7; 9; 13
(2008/06/13)
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- Peptidyl allyl sulfones: A new class of inhibitors for clan CA cysteine proteases
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A new series of peptidyl allyl sulfone inhibitors was discovered while trying to synthesize epoxy sulfone inhibitors from vinyl sulfones using basic oxidizing conditions. The various dipeptidyl allyl sulfones were evaluated with calpain I, papain, cathepsins B and L, cruzain and rhodesain and found to be potent inhibitors. In comparison to the previously developed class of vinyl sulfone inhibitors, the novel dipeptidyl allyl sulfones were more potent inhibitors than the corresponding dipeptidyl vinyl sulfones. It was observed that the stereochemistry of the vinyl sulfone precursor played a role in the potency of the dipeptidyl allyl sulfone inhibitor.
- G?tz, Marion G.,Caffrey, Conor R.,Hansell, Elizabeth,McKerrow, James H.,Powers, James C.
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p. 5203 - 5211
(2007/10/03)
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- Radical-mediated silyl- and germyldesulfonylation of vinyl and (α-fluoro)vinyl sulfones: Application of tris(trimethylsilyl)silanes and tris(trimethylsilyl)germanes in Pd-catalyzed couplings
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Equation presented. Radical-mediated silyl- and germyldesulfonylations of various vinyl and (α-fluoro)vinyl sulfones with tris(trimethylsilyl)silane and germanium hydrides provide access to vinyl and (α-fluoro)vinyl silanes and germanes. Upon oxidative treatment with hydrogen peroxide in basic aqueous solution, the vinyl tris(trimethylsilyl)silanes and -germanes undergo Pd-catalyzed cross-couplings with aryl halides.
- Wnuk, Stanislaw F.,Garcia Jr., Pedro I.,Wang, Zhizhong
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p. 2047 - 2049
(2007/10/03)
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- Cysteine protease inhibitors for use in treatment of IGE mediated allergic diseases
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PCT No. PCT/GB96/01707 Sec. 371 Date Feb. 26, 1998 Sec. 102(e) Date Feb. 26, 1998 PCT Filed Jul. 17, 1996 PCT Pub. No. WO97/04004 PCT Pub. Date Feb. 6, 1997The invention provides compounds for use in the treatment of allergic diseases including juvenile asthma and eczema. The compounds can inhibit IgE mediated reaction to major environmental and occupational allergens and can also have a prophylactic effect against allergic disease by preventing allergic sensitization to environmental and occupational allergens when administered to at-risk individuals (e.g., those at genetic risk of asthma and those exposed to occupational allergens in the workplace). The compounds are also useful for inactivation or attenuation of the allergenicity of allergens in situ. The invention provides compounds and ligands per se, pharmaceutical compositions containing the compounds, processes for producing the compounds and pharmaceutical compositions, and methods for using the compounds and compositions in treatment or prophylaxis of IgE mediated allergic diseases and in inactivation or attenuation of allergens in situ. The invention also enables the reduction or destruction of the viability of allergy-causing organisms.
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- Stereoselective epoxidation of vinyl sulfones and N-(p-tolylsulfonyl)-vinylsulfoximines derived from isopropylideneglyceraldehyde: Synthesis of chiral building blocks
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Epoxidation of N-(p-tolylsulfonyl)vinylsulfoximines using metal alkyl peroxides proceeds with varying degrees of stereoselectivity, depending both on the metal cation and the steric bulk of the alkyl peroxide group. The stereochemical outcome of the epoxidation of substrates bearing an allylic asymmetric centre is also dependent upon the epoxidising agent, and very high levels of stereoselectivity may be obtained in the formation of sulfonyloxirane 8a. This oxirane was subsequently converted into the sulfonyloxirane 15, a precursor to a useful chiral functionalised acyl anion equivalent. In addition, the optically pure α-bromothioester 20 was also prepared.
- Briggs, Andrew D.,Jackson, Richard F. W.,Brown, Paul A.
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p. 4097 - 4102
(2007/10/03)
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- Direct sulfonylation of lithiated alkyl phosphonates with benzenesulfonyl fluoride; Facile method for preparation of α-sulfonyl alkyl phosphonates and vinyl sulfones
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α-Sulfonyl phosphonates were synthesized by direct sulfonylation of lithiated alkyl phosphonates with benzenesulfonyl fluoride which have shown different reactivity from benzenesulfonyl chloride, generally known as a sulfonylating reagent.
- Jang, Won Bum,Jeon, Hyoung Joon,Oh, Dong Young
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p. 1253 - 1256
(2007/10/03)
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- Reactive dienophiles containing a difluoromethylenephosphonato group
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New dienophiles containing the difluoromethylenephosphonato group are synthesised from readily-available starting materials and cycloadditions with reactive dienes are executed successfully.
- Blades, Kevin,Lequeux, Thierry P.,Percy, Jonathan M.
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p. 1457 - 1458
(2007/10/03)
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- Free radical desulfenylation and deselenylation of α-sulfur and α-seleno substituted phosphonates with the n-Bu3SnH/AIBN reagents system.
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Selestive desulfenylation and deselenylation of α-sulfur- and α-seleno-substituted phosphonates under free radical condition are described.Chemoselectivity and scope of title reaction were studied using phosphonates additionaly functionalized in the α-position alkyl, phenyl,ethoxy,chloro,carbonyl and sulfenyl groups.It was found the reduction of a halogen tolerates the presence of the sulfenyl group and the latter could be reduced in the presence of the sulfinyl and sulfonyl moieties.Moreover,one sulfenyl group was selectively removed from α-phosphoryl dithioacetals and the phenylsulphenyl group was reduced preferentially in the presence of the methylsulfenyl one. Key words:Desulfenylation,deselenylation,α-phosphoryl sulfides,α-phosphoryl selenides, tri-n-butyltinhydride,α,α-azaisobutyronitrile.
- Balczewski,Piotr
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p. 113 - 122
(2007/10/03)
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- Approaches to the Synthesis of Retronecine from Some Pyrrolidine Precursors
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Procedures are described for the attempted conversion of the pyrrolidine (2) into a bicyclic system that would ultimately lead to retronecine (3). The only molecule to be isolated from these attempts was the epimeric ketone (6), and AM1 and MM2 calculations were used to probe this apparently favoured isomerization. Alternative procedures were then investigated that sought to convert the pyrrolidine (1) into precursors to retronecine, and notable successes were obtained with the addition of the amine (21) to both nitroethene and ethyl 2-diethylphosphonoacrylate. However, not only were these precursors resistant to further transformations into retronecine, but also the problem of epimerization again arose. Consequently, AM1 calculations were again employed, and an X-ray structure determination of ethyl (7R,8R)-7-benzyloxy-1-benzyloxymethyl-5,6,7,8-tetrahydro-3H-pyrrolizine-2-carboxylate (39) is reported. Attempts to convert (39) into a diastereoisomer of retronecine were unsuccessful.
- Clare, Brian W.,Ferro, Vito,Skelton, Brian W.,Stick, Robert V.,White, Allan H.
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p. 805 - 824
(2007/10/02)
-
- α-FUNCTIONAL CYCLOALKYLPHOSPHONATES. I. SYNTHESIS
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Cycloalkylphosphonates 2 of different sizes (from cyclopropyl to cycloheptyl) bearing various functional groups Z in α-position were synthesized by bis-alkylation of α-functional methylphosphonates 1 and ω-dibromoalkanes in presence of base.The choice of the basic system is determined by the nature of Z.With powerful electron-withdrawing groups, NaH-THF/DMSO (Method A, for Z = CN, SO2R) or liquid-solid phase transfer process proved to be the more suitable systems.For Z = aryl or SR, lithium diisopropylamide is required to achieve the deprotonation.A wide range of new phoshonates were obtained in high yields on preparative scale.
- Nasser, Jamal,About-Jaudet, Elie,Collignon, Noel
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p. 171 - 179
(2007/10/02)
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- Total Synthesis of (+/-)-Fawcettimine
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(+/-)-Fawcettimine (7) has been prepared in 13 steps from cyano enone 14 along the line: 14 16 17 19 22 23 24 25 35 42 43 45 54 7.The overall yield is 16.6percent, and no protecting groups are required in the synthesis.The tautomeric ring-chain equilibria of keto carbinolamines 7, 57, and 60 and diketo amines 56 and 59 have been investigated by NMR spectroscopy and molecular mechanics calculations.In the 4R ("epi") series, diketo amine 56 seems to predominate over keto carbinolamine form 57.Isomer 60 cannot be observedspectrally, and the molecular mechanics calculations suggest that it should be 5 kJ/mol less stable than 57.These experiments and calculations are in agreement with the observation that compound 54 exists wholly in the keto amine form, with none of the carbinolamine tautomer being observable spectrally.In the 4S ("natural") series, the keto carbinolamine form 7 greatly predominantes over the diketo amine form 59.
- Heathcock, Clayton H.,Blumenkopf, Todd A.,Smith, Karl M.
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p. 1548 - 1562
(2007/10/02)
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- AN EFFICIENT PREPARATION OF DIETHYL PHENYLSULFONYLMETHYLPHOSPHONATE
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A simple, efficient, and inexpensive method for the preparation of diethyl phenylsulfonylmethylphosphonate (4a), and derivatives thereof, is described.
- Blumenkopf, Todd A.
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p. 139 - 148
(2007/10/02)
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- On the Reaction of 2-Pyrrolecarbaldehyde with Hetero-substituted Ethenes
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3H-Pyrrolizines 1 have been obtained from reactions of 2-pyrrolecarbaldehyde with ethenylphosphonates 2 and the phosphane oxide 5, respectively, the ratio of products depending on the structure of the educts.On varying the reaction conditions a controlled synthesis of both isomers 1e/f was achieved.Pyrrolizines, formed in a reaction of 2-pyrrolecarbaldehyde with ethenyl phenyl sulfone (3), could not be isolated since the reaction proceeded to give more complex pyrrolizine derivatives and the cyclazine 11.A mechanism is proposed for this multistep reaction.N-Alkylatio n of 2-pyrrolecarbaldehyde with dihaloalkanes has been carried out using phase transfer catalysis.
- Flitsch, Wilhelm,Lubisch, Wilfried
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p. 1424 - 1435
(2007/10/02)
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- Synthesis of α,β-γ,δ-unsaturated sulfones and sulfoxides via the Horner-Emmons reaction
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α,β-γ,δ-Unsaturated sulfones and sulfoxides have been prepared via the Horner-Emmons reaction of α,β-unsaturated carbonyl compounds with α-phosphoryl sulfones and sulfoxides.
- Jong, B. E. de,Koning, H. de,Huisman, H. O.
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p. 410 - 414
(2007/10/02)
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