- Stereoselective synthesis of protected l- and d-dideoxysugars and analogues via Prins cyclisations
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A de novo approach for the rapid construction of orthogonally protected l- and d-deoxysugars and analogues is described. A novel and robust silicon-acetal undergoes Prins cyclisations with a series of homoallylic alcohols in high yield and excellent stereocontrol. Modified Tamao-Fleming oxidation of the resulting silyltetrahydropyrans gives direct access to deoxyglycoside analogues and the approach was showcased in the synthesis of protected l-oliose, a component of the anticancer agent aclacinomycin A.
- Beattie, Ryan J.,Hornsby, Thomas W.,Craig, Gemma,Galan, M. Carmen,Willis, Christine L.
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- Total Synthesis of Citreochlorol Monochloro Analogues via a Catalytically Enantioselective Carbonyl Allylation
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An efficient synthetic route to citreochlorol analogues, halogenated polyketide secondary metabolites, is described. The key features are Krische s enantioselective carbonyl allylation, IBr-promoted cyclization, and regioselective epoxide opening. The importance of the route lies in accessing a versatile epoxy ether that enables the formation of citreochlorol monochloro derivatives.
- Hsieh, Bing-Han,Lin, Cheng-Kun,Wu, Chun-Fu
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- Scalable Synthesis of l - Allo -Enduracididine: The Unusual Amino Acid Present in Teixobactin
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A scalable synthesis of l - allo -enduracididine is achieved from commercially available (S)-glycidol in ten linear steps involving well-established synthetic transformations. The synthetic route is flexible and can be used to synthesize all four diastere
- Gangathade, Namdeo,Nayani, Kiranmai,Bukya, Hemalatha,Mainkar, Prathama S.,Chandrasekhar, Srivari
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p. 1465 - 1468
(2021/07/14)
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- COMPOUNDS AND METHODS FOR THE TREATMENT OF PARASITIC DISEASES
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Provided herein are compounds useful for the treatment of various parasitic diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compostions, veterinary compositions and may be used in methods
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- (-)-Tarchonanthuslactone: Design of New Analogues, Evaluation of their Antiproliferative Activity on Cancer Cell Lines, and Preliminary Mechanistic Studies
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Natural products containing the α,β-unsaturated δ-lactone skeleton have been shown to possess a variety of biological activities. The natural product (-)-tarchonanthuslactone (1) possessing this privileged scaffold is a popular synthetic target, but its biological activity remains underexplored. Herein, the total syntheses of dihydropyran-2-ones modeled on the structure of 1 were undertaken. These compounds were obtained in overall yields of 17-21 % based on the Keck asymmetric allylation reaction and were evaluated in vitro against eight different cultured human tumor cell lines. We further conducted initial investigation into the mechanism of action of selected analogues. Dihydropyran-2-one 8 [(S,E)-(6-oxo-3,6-dihydro-2H-pyran-2-yl)methyl 3-(3,4-dihydroxyphenyl)acrylate], a simplified analogue of (-)-tarchonanthuslactone (1) bearing an additional electrophilic site and a catechol system, was the most cytotoxic and selective compound against six of the eight cancer cell lines analyzed, including the pancreatic cancer cell line. Preliminary studies on the mechanism of action of compound 8 on pancreatic cancer demonstrated that apoptotic cell death takes place mediated by an increase in the level of reactive oxygen species. It appears as though compound 8, possessing two Michael acceptors and a catechol system, may be a promising scaffold for the selective killing of cancer cells, and thus, it deserves further investigation to determine its potential for cancer therapy. Fighting the big C: We describe the synthesis of a new family of analogues based on the scaffold of the natural product (-)-tarchonanthuslactone; these compounds were evaluated in vitro against tumor cell lines. We further conducted an initial investigation into the mechanism of action, including the inhibition of phosphatases and glutathione-S-transferase and the production of reactive oxygen species.
- Toneto Novaes, Luiz Fernando,Martins Avila, Carolina,Pelizzaro-Rocha, Karin Juliane,Vendramini-Costa, Débora Barbosa,Pereira Dias, Marina,Barbosa Trivella, Daniela Barreto,Ernesto De Carvalho, Jo?o,Ferreira-Halder, Carmen Veríssima,Pilli, Ronaldo Aloise
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p. 1687 - 1699
(2015/10/06)
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- ARYL FUSED LACTAMS AS EZH2 MODULATORS
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This invention relates to compounds of Formula (I) in which R1, R2, R3, R4, X and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.
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- Stereoselective synthesis of the C1-C12 subunit of (-)-callystatin A
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A stereoselective synthesis of the C1-C12 fragment of callystatin A is disclosed. The two stereocenters at C5 and C10 were created by an organocatalytic reaction and a diastereoselective alkylation, respectively. The trisubstituted double bond was introdu
- Raghavan, Sadagopan,Rajendar, Sheelamanthula
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p. 4371 - 4373
(2015/06/22)
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- Coibacins a and b: Total synthesis and stereochemical revision
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The interface between synthetic organic chemistry and natural products was explored in order to unravel the structure of coibacin A, a metabolite isolated from the marine cyanobacterium cf. Oscillatoria sp. that exhibits selective antileishmanial activity and potent antiinflammatory properties. Our synthetic plan focused on a convergent strategy that allows rapid access to the desired target by coupling of three key fragments involving E-selective Wittig and modified Julia olefinations. CD measurements and comparative HPLC analyses of the natural product and four synthetic stereoisomers led to determination of its absolute configuration, thus correcting the original assignment at C-5 and unambiguously establishing those at C-16 and C-18. Additionally, we synthesized coibacin B on the basis of the assignment of configuration for coibacin A.
- Carneiro, Vania M. T.,Avila, Carolina M.,Balunas, Marcy J.,Gerwick, William H.,Pilli, Ronaldo A.
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p. 630 - 642
(2014/04/03)
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- ARYL AND HETEROARYL FUSED LACTAMS
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This invention relates to compounds of general formula (I) in which R1, R2, U, V, L, M, R5, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.
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- Concise synthesis of acetal-protected syn 1,3-diols by a tandem hemiacetal formation/Tsuji-Trost reaction
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Designed, developed, and applied: A novel domino sequence was used for the rapid assembly of acetal-protected syn 1,3-diols. The convergent synthesis of a polyol fragment of the macrolide antibiotic RK-397 demonstrates that this method is suitable for the rapid and stereoselective preparation of polyketide-type diol motifs.
- Wang, Liang,Menche, Dirk
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p. 9425 - 9427
(2012/10/30)
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- An efficient synthesis of synargentolide A from D-mannitol
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An efficient synthesis of synargentolide A is described by using d-mannitol and d-malic acid. The key features of the synthetic strategy include Wittig olefination, ring closing-metathesis reaction and cross-metathesis reaction for the formation of synarg
- Kamal, Ahmed,Balakrishna, Moku,Reddy, Papagari Venkat,Faazil, Shaikh
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experimental part
p. 2517 - 2523
(2011/02/22)
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- Catalytic enantioselective allyl- and crotylboration of aldehydes using chiral diol·SnCl4 complexes. Optimization, substrate scope and mechanistic investigations
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We report a novel class of C2-symmetric chiral diols derived from the hydrobenzoin skeleton. The combination of these diols with SnCl 4 under Yamamoto's concept of Lewis acid assisted Bronsted acidity (LBA catalysis) leads to high levels of asymmetric induction in the allylboration of aldehydes by commercially available allylboronic acid pinacol ester 1a. The corresponding homoallylic alcohol products of synthetically useful aliphatic aldehydes are obtained in excellent yields with up to 98:2 er. This combined acid manifold is also efficient in catalyzing the diastereo- and enantioselective crotylboration of aldehydes, thus providing the propionate units in >95:5 dr and up to 98:2 er. The X-ray crystal structure of the optimal diol·SnCl4 complex, Vivol (4m)·SnCl 4, unambiguously shows the Bronsted acidic character of this LBA catalyst and its highly dissymmetrical environment. Further controls have ruled out a possible boron transesterification mechanism with the chiral diol and point to LBA catalyst-derived activation of the pinacol allylic boronates 1. Due to slow dissociation of the diol·SnCl4 complex, a small excess of diol is required in order to suppress a competing racemic cycle catalyzed by free SnCl4.
- Rauniyar, Vivek,Zhai, Huimin,Hall, Dennis G.
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supporting information; scheme or table
p. 8481 - 8490
(2009/02/02)
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- Synthesis of the C1-C52 fragment of amphidinol 3, featuring a β-alkoxy alkyllithium addition reaction
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(Chemical Equation Presented) An advanced intermediate for the synthesis of amphidinol 3 has been prepared. A cross-metathesis reaction was used to couple the C1-C12 and C13-C26 segments. An unusual β-alkoxy alkyllithium reagent was generated from this se
- Huckins, John R.,De Vicente, Javier,Rychnovsky, Scott D.
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p. 4757 - 4760
(2008/03/14)
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- 4,5-Didehydro-7-silyloxymethyl-2-oxepanone and formal total syntheses of Hagen's gland lactones and trans-kumausynes
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A concise and enantiospecific route to the 2,6-dioxabicyclo[3.3.0]octan-3-one ring system from commercially available (R)-(+)- and (S)-(-)-glycidols is described. The key features involve ring closing metathesis to construct the 7-substituted-4,5-dehydro-
- Agrawal, Divya,Sriramurthy, Vardhineedi,Yadav, Veejendra K.
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p. 7615 - 7618
(2007/10/03)
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- Total synthesis of (R)-(+)-goniothalamin and (R)-(+)-goniothalamin oxide: first application of the sulfoxide-modified Julia olefination in total synthesis
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A short and efficient synthesis of (R)-(+)-goniothalamin 1 and (R)-(+)-goniothalamin oxide 2 is described. During this approach, the sulfoxide-modified Julia olefination was used as a key step to connect aldehyde 5 to sulfoxide 6. The desired styryl-containing adduct is obtained in good yield and with excellent E/Z selectivity.
- Pospí?il, Ji?í,Markó, István E.
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p. 5933 - 5937
(2007/10/03)
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- Scope and limitations of the scandium-catalyzed enantioselective addition of chiral allylboronates to aldehydes
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Scandium triflate catalyzes the addition of camphor-derived allyl-, methallyl-, and crotylboronates to aldehydes to provide homoallylic alcohols with excellent diastereo- and enantioselectivity. Aromatic, aliphatic, and propargylic aldehydes can be used successfully in this system. Additional advantages of the camphor-diol allylboronates are their ease of synthesis, their availability in both enantiomeric forms, and their stability towards silica gel chromatography. The usefulness of this methodology is further demonstrated by the gram-scale synthesis of various homoallylic alcohols of high enantiomeric excess and by the concise synthesis of the pheromone (4S)-2-methyloctan-4-ol. 1 Introduction 2 Results and Discussion 2.1 Optimization 2.2 Substrate Scope 2.3 Synthetic Applications 2.4 Mechanistic Considerations 3 Conclusion.
- Gravel, Michel,Lachance, Hugo,Lu, Xiaosong,Hall, Dennis G.
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p. 1290 - 1302
(2007/10/03)
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- Scandium-catalyzed allylboration of aldehydes as a practical method for highly diastereo- and enantioselective construction of homoallylic alcohols
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A general approach for the allylation of aldehydes using stable, air-tolerant camphor-based chiral allylboronates under Sc(OTf)3 catalysis is described. This practical methodology provides both syn and anti propionate units and other homoallylic alcohols with very high levels of diastereo- and enantioselectivity for several substrates, including functionalized aliphatic aldehydes useful toward the elaboration of complex natural products. Copyright
- Lachance, Hugo,Lu, Xiaosong,Gravel, Michel,Hall, Dennis G.
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p. 10160 - 10161
(2007/10/03)
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- An expeditious and efficient procedure for the synthesis of unsaturated acyclonucleosides of Z configuration related to D4T
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Enantiopure 2,5-dihydrofuran derivatives were prepared from (S)-glycidol through a new reaction sequence involving epoxide opening with a vinylcuprate, selenium-induced cyclization to give exclusively the 5-endo product, and regioselective selenoxide elimination. Unsaturated acyclonucleosides of Z configuration were obtained in a straight-forward manner by treating 2,5-dihydrofuran with iodotrimethylsilane in the presence of silylated purinic or pyrimidinic bases. This synthetic process involves opening of the dihydrofuran ring by trimethylsilyl iodide and substitution of iodine by the nucleic base in a single reaction step.
- Bravo, Fernando,Viso, Antonio,Castillon, Sergio
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p. 1172 - 1175
(2007/10/03)
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- First total synthesis and determination of the absolute configuration of strictifolione, a new 6-(ω-phenylalkenyl)-5,6-dihydro-α-pyrone, isolated from Cryptocarya strictifolia
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Starting from (S)-malic acid and (S)-glycidol, the first total synthesis of strictifolione, a new 6-(ω-phenylalkenyl)-5,6-dihydro-α-pyrone isolated from Cryptocarya strictifolia, was accomplished, which confirmed its structure including the absolute confi
- Juliawaty, Lia Dewi,Watanabe, Yoshimi,Kitajima, Mariko,Achmad, Sjamsul Arifin,Takayama, Hiromitsu,Aimi, Norio
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p. 8657 - 8660
(2007/10/03)
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- Synthesis of (R)-(-)-argentilactone
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A synthesis of (R)-(-)-argentilactone is reported starting from the (S)-enantiomer of glycidol. The synthesis is based on ring closing metathesis of the acrylic ester of (R)-1-O-(tert-butyldiphenylsilyl)-4-penten-1,2-diol 4.
- Hansen, Trond Vidar
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p. 547 - 550
(2007/10/03)
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- The olefin metathesis approach to epothilone A and its analogues
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The olefin metathesis approach to epothilone A (1) and several analogues (39-41, 42-44, 51-57, 58-60, 64-65, and 67-69) is described. Key building blocks 6-8 were constructed in optically active form and were coupled and elaborated to olefin metathesis pr
- Nicolaou,He,Vourloumis,Vallberg,Roschangar,Sarabia,Ninkovic,Yang,Trujillo
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p. 7960 - 7973
(2007/10/03)
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- Durch Olefinmetathese zum Epothilongeruest
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Keywords: Cyclisierungen; Epothilone; Naturstoffe; Olefinmetathese; Synthesemethoden
- Nicolaou, K. C.,He, Yun,Vourloumis, Dionisios,Vallberg, Hans,Yang, Zhen
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p. 2554 - 2556
(2007/10/03)
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- Asymmetric Synthesis Using Tartrate Ester Modified Allylboronates. 2. Single and Double Asymmetric Reactions with Alkoxy-Substituted Aldehydes
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The reactions of tartrate allylboronates 1a and 1b with a series of chiral and achiral alkoxy-substituted aldehydes are described.It is shown that conformationally unrestricted α- and β-alkoxy aldehyde substituents have a significant, negative impact on the stereoselectivity of the asymmetric allylborations.For example, α-alkoxy aldehydes 25-27 and β-alkoxy aldehydes 28-30 undergo asymmetric allylborations with 1 in only 56-59percent and 63-66percent ee, respectively, while the reactions of 1 and aliphatic aldehydes such as decanal or cyclohexane-carboxaldehyde proceed in 86-87percent ee under the same conditions.Evidence of reduced stereoselection is also apparent in the double diastereoselectivity data reported in Table I and Scheme I for the asymmetric allylborations of chiral β-alkoxy aldehydes 16 and 19 and chiral α-alkoxy aldehyde 22.In contrast, chiral aldehydes containing alkoxy groups that are conformationally constrained by incorporation in rings, as in glyceraldehyde acetonide 4,4-deoxythreose ketal 7, and α,β-epoxy aldehydes 10 and 13, are excellent allylboration substrates, with diastereoselection in the cases of 4 and 7 being significantly greater than that obtained with simpler achiral substrates.A model that rationalizes this "alkoxy effect" is presented.Specifically, it is inferred that the observed trends in stereoselection are not steric in origin, but rather that unfavorable lon pair/lone pair interactions occur between the tartrate ester carbonyl and alkoxy substituents particularly of conformationally unconstrained aldehyde substrates (e.g., 16, 19, 22, 25-30) that results in diminished reaction stereoselection (see transition structures 58 and 61).For substrates with conformationally constrained alkoxy substituents , e.g. 4 and 7, favorable lone pair/dipole interactions between the tartrate ester carbonyl and the backside of the β-alkoxy C-O bond leads to increased stabilization of the favored transition state (see transition structures 59 and 60) and hence to increased reaction diastereoselection.A simple method for the analysis of the average diastereofacial selectivity of a chiral reagent in a pair of double asymmetric reactions is also presented.This analysis, which is independent of the intrinsic diastereofacial bias of the chiral aldehyde, enables one to make direct comparisons of the relative diastereoselectivities of a range of chiral substrates with a given chiral reagent (or vice versa).In this way, double diastereoselcetivity data are easily analyzed to determine if the chiral reagent/chiral substrate pair is "well behaved" compared to typical achiral substrate reference systems, thereby providing insight into the structural features that influence reaction stereoselectivity.
- Roush, William R.,Hoong, Lee K.,Palmer, Michelle A. J.,Straub, Julie A.,Palkowitz, Alan D.
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p. 4117 - 4126
(2007/10/02)
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