- An Esterase-like Lyase Catalyzes Acetate Elimination in Spirotetronate/Spirotetramate Biosynthesis
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Spirotetronate and spirotetramate natural products include a multitude of compounds with potent antimicrobial and antitumor activities. Their biosynthesis incorporates many unusual biocatalytic steps, including regio- and stereo-specific modifications, cyclizations promoted by Diels–Alderases, and acetylation-elimination reactions. Here we focus on the acetate elimination catalyzed by AbyA5, implicated in the formation of the key Diels–Alder substrate to give the spirocyclic system of the antibiotic abyssomicin C. Using synthetic substrate analogues, it is shown that AbyA5 catalyzes stereospecific acetate elimination, establishing the (R)-tetronate acetate as a biosynthetic intermediate. The X-ray crystal structure of AbyA5, the first of an acetate-eliminating enzyme, reveals a deviant acetyl esterase fold. Molecular dynamics simulations and enzyme assays show the use of a His-Ser dyad to catalyze either elimination or hydrolysis, via disparate mechanisms, under substrate control.
- Lees, Nicholas R.,Han, Li-Chen,Byrne, Matthew J.,Davies, Jonathan A.,Parnell, Alice E.,Moreland, Pollyanna E. J.,Stach, James E. M.,van der Kamp, Marc W.,Willis, Christine L.,Race, Paul R.
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supporting information
p. 2305 - 2309
(2019/01/29)
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- Amidation of unactivated ester derivatives mediated by trifluoroethanol
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A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity.
- McPherson, Christopher G.,Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
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supporting information
p. 3507 - 3518
(2017/04/26)
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- A Native Ternary Complex Trapped in a Crystal Reveals the Catalytic Mechanism of a Retaining Glycosyltransferase
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Glycosyltransferases (GTs) comprise a prominent family of enzymes that play critical roles in a variety of cellular processes, including cell signaling, cell development, and host-pathogen interactions. Glycosyl transfer can proceed with either inversion
- Albesa-Jov, David,Mendoza, Fernanda,Rodrigo-Unzueta, Ane,Gomolln-Bel, Fernando,Cifuente, Javier O.,Urresti, Saioa,Comino, Natalia,Gmez, Hansel,Romero-Garca, Javier,Lluch, Jos M.,Sancho-Vaello, Enea,Biarns, Xevi,Planas, Antoni,Merino, Pedro,Masgrau, Laura,Guerin, Marcelo E.
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supporting information
p. 9898 - 9902
(2015/08/19)
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- Tetrapropylammonium perruthenate catalyzed glycol cleavage to carboxylic (Di)acids
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A new method to accomplish glycol cleavage to carboxylic (di)acids in one step using catalytic amounts of tetrapropylammonium perruthenate (TPAP) together with N-methylmorpholine N-Oxide (NMO) as the stoichiometric oxidant is presented. In addition to regenerating the active catalyst, the N-oxide stabilizes intermediary carbonyl hydrates and thereby shifts a crucial equilibrium. The mild oxidation protocol is applicable to a broad range of substrates providing the respective acids, diacids, or keto acids in high yields.
- Schmidt, Andrea-Katharina C.,Stark, Christian B. W.
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supporting information; experimental part
p. 5788 - 5791
(2011/12/05)
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- d- and l-Serine, useful synthons for the synthesis of 24-hydroxyvitamin D3 metabolites. A formal synthesis of 1α,24R,25-(OH)3-D3, 24R,25-(OH)2-D3 and 24S,25-(OH)2-D3
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d- and l-Serine have been used for the enantioselective synthesis of tosylates 7a and 7b, useful building blocks for the synthesis of triols 5a and 5b which have already been obtained via a diastereoselective synthesis and used for the synthesis of 2a, 2b and 2c. We have thus performed a formal synthesis of 24S,25-(OH)2-D3, 24R,25-(OH)2-D3 and 1α,24R,25-(OH)3-D3.
- Fernandez, Carlos,Gándara, Zoila,Gómez, Generosa,Covelo, Berta,Fall, Yagamare
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p. 2939 - 2942
(2008/02/03)
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- Hydrolytic kinetic resolution of epoxides catalyzed by chromium(III)-endo, endo-2,5-diaminonorbornane-salen [Cr(III)-DIANANE-salen] complexes. Improved activity, low catalyst loading
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The hydrolytic kinetic resolution (HKR) of terminal epoxides, using chiral chromium(III)-salen catalysts based on DIANANE (endo,endo-2,5-diaminonorbornane) , was studied. A broad substrate scope was found for the chromium(III)-DIANANE catalysts, and very low loadings (down to 0.05 mol%) were needed to achieve high enantiomeric purities of both the remaining epoxides and the product diols (up to >99% ee). Besides monosubstituted epoxides, 2-methyl-2-n-pentyloxirane, which is an example for 2,2-disubstituted epoxides, could be ring-opened in an asymmetric fashion with water in the presence of an electronically tuned chromium-(III)-DIANANE complex.
- Berkessel, Albrecht,Ertuerk, Erkan
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p. 2619 - 2625
(2007/10/03)
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- PROCESS FOR THE ENZYMATIC RESOLUTION OF 1,3-DIOXOLANE-4-CARBOXYLATES
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The present invention relates to enzymatic' resolution of enantiomeric mixtures of 1,3-dioxolane-4-carboxylate esters of Formula I. More particularly, the present invention relates to a process for preparing R and S enantiomers of methyl 2,2-dimethyl-1,3-dioxolane-4-carboxylate in high optical purity.
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- Selective inhibition of Trypanosoma brucei GAPDH by 1,3-bisphospho-D-glyceric acid (1,3-diPG) analogues
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Various phosphono-phosphates and diphophonates were synthesized as 1,3-diphosphoglycerate 1,3-diPG) analogues by using a β-ketophosphonate, an α-fluoro,β-ketophosphonate or a β-ketophosphoramidate to mimic the unstable carboxyphosphate part of the natural
- Ladame, Sylvain,Bardet, Michel,Périé, Jacques,Willson, Michèle
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p. 773 - 783
(2007/10/03)
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- A β-lactam-based stereoselective access to β,γ-dihydroxy α-amino acid-derived peptides with either α,β-like or unlike configurations
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A concise access to α,β-dihydroxy α-amino acid-derived N-carboxy anhydrides (NCAs) with either like or unlike relative configuration is described. The key steps of the synthetic route are the preparation of the nonracemic 4-alkenyl β-lactams, through either Homer-type olefination of a common 4-formyl β-lactam or the Corey-Winter alkene synthesis applied to 4-dihydroxyalkyl β-lactams, followed by the Sharpless AD reaction, and a subsequent ring expansion of the corresponding 4-substituted 3-hydroxy β-lactams promoted by TEMPO. The opening of thus-prepared NCAs upon treatment with different O- and N-nucleophiles, including α-amino esters which lead to peptides, has also been studied under various reaction conditions.
- Palomo,Oiarbide,Landa,Esnal,Linden
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p. 4180 - 4186
(2007/10/03)
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- Asymmetric synthesis of RK-682 and its analogs, and evaluation of their protein phosphatase inhibitory activities
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We report an asymmetric synthesis of a potent tyrosine phosphatase inhibitor, RK-682 and its analogs. The absolute stereochemistry of RK-682 was determined to be (R). The inhibitory activities of RK-682 and its analogs, (R)-1a, (S)-1a, (R)-1b and (R)-1c toward various protein phosphatases (VHR, cdc25A, cdc25B, and PPI) are also reported.
- Sodeoka, Mikiko,Sampe, Ruriko,Kagamizono, Terumi,Osada, Hiroyuki
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p. 8775 - 8778
(2007/10/03)
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- Some Unexpected Reactions Involving Diphenylketene
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Diphenylketene reacted with the 2-azabicyclohept-5-enes 5, 6 and 10 by attack on nitrogen to give the piperidones 7, 8 and the cyclopentenols 11 respectively.The same ketene reacted with the cyclohexa-1,3-dienes 16 and 17 to give significant amounts of the addition products 20 and 21 respectively.The initially formed product from the cycloaddition of the enol ether 23 and diphenylketene is unstable, rearranging to produce the unsaturated ester 24.
- Maurya, Rakesh,Pittol, Carlos A.,Pryce, Robert J.,Roberts, Stanley M.,Thomas, Russell J.,Williams, Julian O.
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p. 1617 - 1622
(2007/10/02)
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- A Synthesis of (+/-)-Demethoxydaunomycinone
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2-Acetyl-1,4-dihydroxyanthracene-9,10-dione 1 is converted into (+/-)-demethoxydaunomycinone by substitution with 3,3-dimethoxy-1-nitrobutan-2-one, aldol cyclisation, reduction and hydrolysis.The chiral inductions at C-10 realised on cyclisation of 5 and
- Carr, Kathryn,Greener, Neil A.,Mullah, Khairuzzaman, B.,Somerville, Fiona M.,Sutherland, James K.
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p. 1975 - 1980
(2007/10/02)
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- SYNTHESIS OF (24R)-24,25-DIHYDROXYVITAMIN D3
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Two versions of the stereoselective synthesis of (24R)-24,25-dihydroxyvitamin D3 were realized.Vitamin D2 and ergosterol were used as starting materials.Methods are proposed for the production of the following key compounds: 6-Methoxy-23,24-bisnor-9,10-seco-3,5-cyclochola-7,10(19)-dien-22-yl phenyl sulfone; 3β-hydroxy-23,24-bisnorchola-5,7-dien-22-yl phenyl sulfone; (2R)-3-methylbutane-1,2,3-triol 1-p-toluenesulfonate.
- Bogoslovskii, N. A.,Samokhvalova, N. G.,Isaeva, T. A.,Valashek, I. E.,Filippova, T. M.,Kharchevnikov, A. P.
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p. 2070 - 2081
(2007/10/02)
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- Oxidative Cleavage of Vicinal Diols at the Nickel Hydroxide Electrode
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Vicinal diols are oxidatively cleaved with good yields by electrolysis at an oxide covered nickel electrode in an aqueous alkaline electrolyte and an undivided cell.The method is applied in the synthesis of optical pure derivatives of 2,2-dimethyl-1,3-dioxolane-4-carboxylic acid.
- Ruholl, Heinrich,Schaefer, Hans J.
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- Convenient One-Pot Conversion of Alcohols into Esters via Hemiacetal Intermediates
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A simple and efficient one-pot oxidative procedure, adaptable to a large scale, is described for the preparation of methyl esters from either primary alcohols or vic-diols.The aldehyde is generated by Swern or periodate oxidation, followed by bromine oxidation of the methyl hemiacetal formed in aqueous methanolic solution.
- Lichtenthaler, Frieder W.,Jarglis, Pan,Lorenz, Klaus
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p. 790 - 792
(2007/10/02)
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- Synthesis and Determination of the Enantiomeric Pyrity of (R)- and (S)-2,3-Dihydroxy-3-methylbutyl p-Toluensulfonate
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(R)- and (S)-2,3-dihydroxy-3-methylbutyl p-toluenesulfonate, used as building blocks for vitamine D3 metabolites and carotenoids, respectively, were resynthesized since differing melting points and optical rotations are reported in the literature.The give
- Schoenecker, Bruno
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p. 705 - 712
(2007/10/02)
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- Optically Active C5-Synthons for the Synthesis of Naturally Occurring Terpenes
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The optically active synthons (S)-22, (R)-23, (R)-25 and (R)-26 were prepared from L-serine.Furthermore the tertiary alcohol 6 was synthesized from L-serine (-> (S)-6) and D-mannitol (-> (R)-6).These compounds are suitable for the synthesis of optically active natural products.
- Dumont, Raymond,Pfander, Hanspeter
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p. 814 - 823
(2007/10/02)
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