- Palladium-catalyzed allylic substitution between C-based nucleophiles and 6-azabicyclo[3.1.0]-hex-3-en-2-oxy derivatives: A new selectivity paradigm
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The reaction between α-hydroxy-(or α-acetoxy) cyclopenten-aziridines (6-azabicyclo[3.1.0]hex-3-en-2-ols or acetates) and C-based nucleophiles in the presence of Pd(0)-catalysis was investigated. In all the cases studied, the reaction was totally regio- and diastereo-selective, affording a single adduct in moderate to good yields. Specifically, attack of the nucleophile at position 3 of the cyclopentene moiety, anti to the vicinal oxy group, with vinylogous ring opening of the aziridine ring, was observed. When the carbon acid is a very acidic methylene (pKa (DMSO) ≤ 7.3), the resulting adduct is a zwitterion, resulting from an intramolecular proton transfer between the amino group and the carbon acid moiety taking place after the C–C bond formation. A plausible mechanism for this transformation is put forward.
- Oliveira, Jo?o A.C.,Kiala, Gredy,Siopa, Filipa,Bernard, Aurélie,Gontard, Geoffrey,Oble, Julie,Afonso, Carlos A.M.,Poli, Giovanni
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- Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)
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The use of mono-substituted malonic acid half oxyesters (SMAHOs) has been hampered by the sporadic references describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access to reagents bearing different substituents at the malonic position, including functionalized derivatives. On the other hand, the development of a monoesterification step of a substituted malonic acid derivative proved to be the best entry for diversity at the ester function, rather than the use of an intermediate Meldrum acid. Both these transformations are characterized by their simplicity and efficiency, allowing a straightforward access to SMAHOs from cheap starting materials.
- Condon, Sylvie,Le Gall, Erwan,Pichon, Christophe,Presset, Marc,Xavier, Tania
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supporting information
p. 2085 - 2094
(2021/09/02)
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- Structural Basis of a Broadly Selective Acyltransferase from the Polyketide Synthase of Splenocin
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Polyketides are a large family of pharmaceutically important natural products, and the structural modification of their scaffolds is significant for drug development. Herein, we report high-resolution X-ray crystal structures of the broadly selective acyltransferase (AT) from the splenocin polyketide synthase (SpnD-AT) in the apo form and in complex with benzylmalonyl and pentynylmalonyl extender unit mimics. These structures revealed the molecular basis for the stereoselectivity and substrate specificity of SpnD-AT, and enabled the engineering of the industrially important Ery-AT6 to broaden its substrate scope to include three new types of extender units.
- Li, Yuan,Zhang, Wan,Zhang, Hui,Tian, Wenya,Wu, Lian,Wang, Shuwen,Zheng, Mengmeng,Zhang, Jinru,Sun, Chenghai,Deng, Zixin,Sun, Yuhui,Qu, Xudong,Zhou, Jiahai
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supporting information
p. 5823 - 5827
(2018/05/14)
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- Quaternary β2,2-Amino Acids: Catalytic Asymmetric Synthesis and Incorporation into Peptides by Fmoc-Based Solid-Phase Peptide Synthesis
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β-Amino acid incorporation has emerged as a promising approach to enhance the stability of parent peptides and to improve their biological activity. Owing to the lack of reliable access to β2,2-amino acids in a setting suitable for peptide synthesis, most contemporary research efforts focus on the use of β3- and certain β2,3-amino acids. Herein, we report the catalytic asymmetric synthesis of β2,2-amino acids and their incorporation into peptides by Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS). A quaternary carbon center was constructed by the palladium-catalyzed decarboxylative allylation of 4-substituted isoxazolidin-5-ones. The N?O bond in the products not only acts as a traceless protecting group for β-amino acids but also undergoes amide formation with α-ketoacids derived from Fmoc-protected α-amino acids, thus providing expeditious access to α-β2,2-dipeptides ready for Fmoc-SPPS.
- Yu, Jin-Sheng,Noda, Hidetoshi,Shibasaki, Masakatsu
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supporting information
p. 818 - 822
(2017/12/26)
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- Facile Hydrogenolysis of C(sp3)–C(sp3) σ Bonds
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The modification of benzylic quaternary, tertiary, and secondary carbon centers through palladium-catalyzed hydrogenolysis of C(sp3)–C(sp3) σ bonds is presented. When benzyl Meldrum's acid derivatives bearing quaternary benzylic centers are treated under mild hydrogenolysis conditions – palladium on carbon and atmospheric pressure of hydrogen – aromatics substituted with tertiary benzylic centers and Meldrum's acid are obtained with good to excellent yield. Analogously, substrates containing tertiary or secondary benzylic centers yield aromatics substituted with secondary benzylic centers or toluene derivatives, respectively. Furthermore, this strategy is used for the high yielding synthesis of diarylmethanes. The scope of the reductive dealkylation reaction is explored and the limitations with respect to steric and electronic factors are determined. A mechanistic analysis of the reaction is described that consisted of deuterium labelling experiments and hydrogenolysis of enantioenriched derivatives. The investigation shows that the C(sp3)–C(sp3) σ bond-cleaving events occur through a hybrid SN1/SN2 mechanism, in which the palladium center displaces a carbon-based leaving group, namely Meldrum's acid, with inversion of configuration, followed by reductive elimination of palladium to furnish a C?H bond. (Figure presented.).
- Fillion, Eric,Beaton, Eric,Nguyen, Yen,Wilsily, Ashraf,Bondarenko, Ganna,Jacq, Jér?me
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p. 3422 - 3434
(2016/11/13)
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- Organocatalysed decarboxylative protonation process from Meldrum's acid: Enantioselective synthesis of isoxazolidinones
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An asymmetric organocatalysed decarboxylative protonation reaction allowed a straightforward synthesis of α-substituted isoxazolidin-5-ones from readily available 5-substituted Meldrum's acids. This process is initiated by an anionic formal (3+2) cycloaddition-fragmentation, generated in-situ from a sulfone-amide precursor which also served as a latent source of proton.
- Tite, Tony,Sabbah, Mohamad,Levacher, Vincent,Briere, Jean-Francois
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supporting information
p. 11569 - 11571
(2013/12/04)
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- Chemistry of diazocarbonyl compounds: XXV. Comparative photochemistry of diazo compounds and sulfur ylides of the 1,3-dioxane-4,6-dione series
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Photochemical decomposition of 2,2-dialkyl-5-diazo-1,3-dioxane-4,6-diones in the presence of pyridine, methanol, or dimethyl sulfide as carbene traps involves mainly the Wolff rearrangement which is likely to follow a concerted pattern, while the yield of the "carbene" products does not exceed 27-28%. No carbene intermediates are formed in the photolysis of the corresponding dioxo sulfonium ylides under analogous conditions, and the main photochemical process is 1,2-methyl shift (Stevens rearrangement), followed by photochemical transformations of the primary products according to the Norrish type II pattern. Pleiades Publishing, Inc., 2006.
- Nikolaev,Shevchenko,Platz,Khimich
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p. 815 - 827
(2007/10/03)
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- Search for dioxocarbenes in photochemical reactions of 5-diazo-4,6-dioxo-1, 3-dioxanes, associated diazirines, and S-ylides
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On direct photolysis of 2,2-dialkyl-5-diazo-4,6-dioxo-1,3-dioxanes in the presence of pyridine, methanol or dimethyl sulfide as carbene traps, the yield of 'carbene' products does not exceed 27-28%. At the same time photochemical transformations of the re
- Shevchenko,Khimich,Platz,Nikolaev
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p. 435 - 438
(2007/10/03)
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