- Genome Mining of Oxidation Modules in trans-Acyltransferase Polyketide Synthases Reveals a Culturable Source for Lobatamides
-
Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are multimodular megaenzymes that biosynthesize many bioactive natural products. They contain a remarkable range of domains and module types that introduce different substituents into growing polyketide chains. As one such modification, we recently reported Baeyer–Villiger-type oxygen insertion into nascent polyketide backbones, thereby generating malonyl thioester intermediates. In this work, genome mining focusing on architecturally diverse oxidation modules in trans-AT PKSs led us to the culturable plant symbiont Gynuella sunshinyii, which harbors two distinct modules in one orphan PKS. The PKS product was revealed to be lobatamide A, a potent cytotoxin previously only known from a marine tunicate. Biochemical studies show that one module generates glycolyl thioester intermediates, while the other is proposed to be involved in oxime formation. The data suggest varied roles of oxygenation modules in the biosynthesis of polyketide scaffolds and support the importance of trans-AT PKSs in the specialized metabolism of symbiotic bacteria.
- Ueoka, Reiko,Meoded, Roy A.,Gran-Scheuch, Alejandro,Bhushan, Agneya,Fraaije, Marco W.,Piel, J?rn
-
supporting information
p. 7761 - 7765
(2020/03/25)
-
- Polycyclic ketone monooxygenase from the thermophilic fungus Thermothelomyces thermophila: A structurally distinct biocatalyst for bulky substrates
-
Regio- and stereoselective Baeyer-Villiger oxidations are difficult to achieve by classical chemical means, particularly when large, functionalized molecules are to be converted. Biocatalysis using flavin-containing Baeyer-Villiger monooxygenases (BVMOs) is a wellestablished tool to address these challenges, but known BVMOs have shortcomings in either stability or substrate selectivity. We characterized a novel BVMO from the thermophilic fungus Thermothelomyces thermophila, determined its three-dimensional structure, and demonstrated its use as a promising biocatalyst. This fungal enzyme displays excellent enantioselectivity, acts on various ketones, and is particularly active on polycyclic molecules. Most notably we observed that the enzyme can perform oxidations on both the A and D ring when converting steroids. These functional properties can be linked to unique structural features, which identify enzymes acting on bulky substrates as a distinct subgroup of the BVMO class.
- Fürst, Maximilian J.L.J.,Savino, Simone,Dudek, Hanna M.,Castellanos, J. Rúben Gómez,De Souza, Cora Gutiérrez,Rovida, Stefano,Fraaije, Marco W.,Mattevi, Andrea
-
supporting information
p. 627 - 630
(2017/05/15)
-
- Direct room-temperature lactonisation of alcohols and ethers onto amides: An "amide strategy" for synthesis
-
Last-minute deal: A direct lactonisation of ethers and alcohols onto amides that proceeds at room temperature under mild conditions is reported (see scheme). This allows the effective saving of up to two unproductive, sequential deprotection operations in synthetic sequences. Mechanistic studies are described, and a new "amide strategy" that exploits the dual robustness/late-stage selective activation properties of this functional group is outlined. Copyright
- Valerio, Viviana,Petkova, Desislava,Madelaine, Claire,Maulide, Nuno
-
supporting information
p. 2606 - 2610
(2013/03/14)
-
- Cascade biotransformations via enantioselective reduction, oxidation, and hydrolysis: Preparation of (R)-δ-lactones from 2-alkylidenecyclopentanones
-
The first cascade biotransformation involving enantioselective reduction of a C=C double bond, Baeyer-Villiger oxidation, and lactone hydrolysis was developed as a green and sustainable tool for synthesizing enantiopure δ-lactones. One-pot cascade biotransformations were achieved with Acinetobacter sp. RS1 containing a novel enantioselective reductase and an enantioselective lactone hydrolase and Escherichia coli coexpressing cyclohexanone monooxygenase and glucose dehydrogenase, converting easily available 2-alkylidenecyclopentanones 1-2 into the corresponding valuable flavors and fragrances (R)-δ-lactones 5-6 in high ee. The one-pot synthesis is better than the reported two-step preparation. This concept is useful in developing other redox cascades with the substrates containing C=C double bond.
- Liu, Ji,Li, Zhi
-
p. 908 - 911
(2013/07/25)
-
- Tandem isomerization-lactonization of olefinic fatty acids using the Lewis acidic ionic liquid, choline chloride·2ZnCl2
-
The tandem isomerization-lactonization of unsaturated fatty acids to their corresponding γ-lactones was carried out for the first time in the presence of a Lewis acidic ionic liquid, choline chloride·2ZnCl 2. The ionic liquid initially catalyzes the stepwise migration of the double bond along the carbon chain toward the carboxyl group at the Δ4 position, which subsequently undergoes lactonization resulting in the formation of γ-lactones. This one step process allows the formation of γ-lactone in good yield with little or no formation of δ-lactones. The studied ionic liquid plays the dual role of solvent as well as catalyst.
- Akula, Shivaraju,Kumar, Pandari Phani,Prasad, Rachapudi B.N.,Kanjilal, Sanjit
-
scheme or table
p. 3471 - 3473
(2012/08/13)
-
- Oxidation of the cyclopentanone and cyclohexanone alkyl derivatives in a pseudohomogeneous system without a phase transfer agent
-
The reaction of catalytic oxidation of C5-C12 alkyl- and cycloalkylcyclopentanones and -cyclohexanones to lactones in a pseudohomogeneous system without the participation of phase transfer agents was investigated. It was established that the catalytic systems prepared on the basis of molybdenum and tungsten blue (MeOnBrm, where Me = Mo, W, n = 1, 2, m = 2, 3) and H3PO4 deposited on powdered activated carbon AG-3 at 40-60°C, at 5-6 h duration exhibit a high selectivity in the reaction of nucleophilic addition of oxygen to the ketones with the formation of the valero- and caprolactones. Pleiades Publishing, Ltd., 2011.
- Alimardanov,Garibov,Abbasov,Sadygov,Abdullaeva,Dzhafarova
-
experimental part
p. 1664 - 1670
(2011/12/02)
-
- Crystal structures of cyclohexanone monooxygenase reveal complex domain movements and a sliding cofactor
-
Cyclohexanone monooxygenase (CHMO) is a flavoprotein that carries out the archetypical Baeyer-Villiger oxidation of a variety of cyclic ketones into lactones. Using NADPH and O2 as cosubstrates, the enzyme inserts one atom of oxygen into the substrate in a complex catalytic mechanism that involves the formation of a flavin-peroxide and Criegee intermediate. We present here the atomic structures of CHMO from an environmental Rhodococcus strain bound with FAD and NADP+ in two distinct states, to resolutions of 2.3 and 2.2 A. The two conformations reveal domain shifts around multiple linkers and loop movements, involving conserved arginine 329 and tryptophan 492, which effect a translation of the nicotinamide resulting in a sliding cofactor. Consequently, the cofactor is ideally situated and subsequently repositioned during the catalytic cycle to first reduce the flavin and later stabilize formation of the Criegee intermediate. Concurrent movements of a loop adjacent to the active site demonstrate how this protein can effect large changes in the size and shape of the substrate binding pocket to accommodate a diverse range of substrates. Finally, the previously identified BVMO signature sequence is highlighted for its role in coordinating domain movements. Taken together, these structures provide mechanistic insights into CHMO-catalyzed Baeyer-Villiger oxidation.
- Mirza, I. Ahmad,Yachnin, Brahm J.,Wang, Shaozhao,Grosse, Stephan,Bergeron, Helene,Imura, Akihiro,Iwaki, Hiroaki,Hasegawa, Yoshie,Lau, Peter C. K.,Berghuis, Albert M.
-
experimental part
p. 8848 - 8854
(2009/12/04)
-
- Investigations of the scope and mechanism of the tandem hydroesterification/lactonization reaction
-
(Chemical Equation Presented) Heating allylic and homoallylic alcohols and 2-pyridylmethyl formate in the presence of Ru3(CO)12 initiates a tandem sequence of hydroesterification and lactonization. Mechanistic studies suggest that regioselectivity and overall reaction efficiency are governed by the relative rates of reductive elimination and β-hydride elimination for the alkylruthenium intermediates.
- Wang, Lijun,Floreancig, Paul E.
-
p. 4207 - 4210
(2007/10/03)
-
- Tandem cross-metathesis/hydrogenation/cyclization reactions by using compatible catalysts
-
(Matrix presented) A one-pot tandem cross-metathesis/hydrogenation/cyclization procedure was achieved at room temperature, under 1 atm of hydrogen, in the presence of a ruthenium catalyst and PtO2 showing the compatibility of the two catalysts. This tandem reaction allows the synthesis of substituted lactones and lactols from acrylic acid and acrolein, respectively, in the presence of unsaturated alcohols.
- Cossy, Janine,Bargiggia, Frederic,BouzBouz, Samir
-
p. 459 - 462
(2007/10/03)
-
- Compounds having protected hydroxy groups
-
The present invention relates to compounds with protected hydroxy groups of formula (I) These compounds are precursors for organoleptic agents, such as fragrances, and masking agents and for antimicrobial agents. When activated, the compounds of formula (I) are cleaved and form one or more organoleptic and/or antimicrobial compounds.
- -
-
-
- Compounds having protected hydroxy groups
-
The present invention relates to compounds with protected hydroxy groups of formula (I) These compounds are precursors for organoleptic agents, such as fragrances, and masking agents and for antimicrobial agents. When activated, the compounds of formula (I) are cleaved and form one or more organoleptic and/or antimicrobial compounds.
- -
-
-
- Stereoselective synthesis of δ-lactones from 5-oxoalkanals via one-pot sequential acetalization, tishchenko reaction, and lactonization by cooperative catalysis of samarium ion and mercaptan
-
By the synergistic catalysis of samarium ion and mercaptan, a series of 5-oxoalkanals was converted to (substituted) δ-lactones in efficient and stereoselective manners. This one-pot procedure comprises a sequence of acetalization, Tishchenko reaction and lactonization. The deliberative use of mercaptan, by comparison with alcohol, is advantageous to facilitate the catalytic cycle. The reaction mechanism and stereochemistry are proposed and supported by some experimental evidence. Such samarium ion/mercaptan cocatalyzed reactions show the feature of remote control, which is applicable to the asymmetric synthesis of optically active δ-lactones. This study also demonstrates the synthesis of two insect pheromones, (2S,5R)-2-methylhexanolide and (R)-hexadecanolide, as examples of a new protocol for asymmetric reduction of long-chain aliphatic ketones.
- Hsu,Fang
-
p. 8573 - 8584
(2007/10/03)
-
- Precursor compounds
-
The compounds of the formula I are precursors for organoleptic and antimicrobial compounds. The latter are generated in the presence of skin bacteria, enzymes or acidic or alkaline conditions. One precursor molecule can provide one or more different compounds.
- -
-
-
- Beta-ketoester compounds
-
The beta-ketoesters of formula I are useful as precursors for organoleptic compounds, especially for flavors, fragrances and masking agents and antimicrobial compounds.
- -
-
-
- One-carbon ring enlargement of lactones
-
Two-step or three-step one-carbon ring enlargement of lactones is realized from lactones and chloromethyl phenyl sulfoxide via a rearrangement of alkylidene carbenoid followed by intramolecular cyclization of the ω- hydroxyalkyl ketene intermediate or via a 2-pyridinethiol ester.
- Satoh, Tsuyoshi,Kurihara, Toshiyuki
-
p. 9215 - 9218
(2007/10/03)
-
- Synthesis and Applications of Tetrahydrofuran-Stable Substituted (3-Lithioxyalkyl)- and (4-Lithioxyalkyl)lithiums, Modified with Magnesium 2-Ethoxyethoxide
-
Substituted hydroxyalkyl phenyl sulfides 3 have been synthesized from the corresponding allylic or homoallylic alcohols 2. Regiospecific cleavage of the C - SPh bond of the sulfides 3 by lithium dispersion in tetrahydrofuran (THF) led to the synthesis of substituted (3-lithioxyalkyl)- and (4-lithioxyalkyl)lithiums 4, most of which share the ω carbon with a carbocyclic ring. The organolithiums were modified with magnesium 2-ethoxyethoxide in order to suppress their reactivity toward THF cleavage, thus offering the advantage of preparing storable ethereal solutions of certain types of (lithioxyalkyl)lithiums. This strategy appears to be of rather broad scope. The functionalized organolithiums prepared in this way react normally with electrophilic reagents with yields in the range 35-55%. Thus, carboxylations of 4 yielded lactones 5, some of which are natural products, while reactions of 4 with benzophenone and cyclic ketones yielded 1,4- and 1,5-diols 6 and 7, respectively.
- Kostas, Ioannis D.,Screttas, Constantinos G.
-
p. 5575 - 5577
(2007/10/03)
-
- Catalytic oxidation of alkyl- and cycloalkylcyclanones into lactones
-
Pilot-plant syntheses of alkyl and cycloalkylcyclanones and their subsequent liquid-phase oxidation into lactones are described. Characteristics of resulting intermediates and target products are reported.
- Abbasov,Alimardanov,Suleimanova
-
p. 621 - 626
(2007/10/03)
-
- Lipase-catalysed Baeyer-Villiger Reactions
-
The Baeyer-Villiger Oxidation of some 2- and 3-substituted cyclopentanones and cyclohexanones using myristic acid and hydrogen peroxide is catalysed by Candida anatarctica lipase.
- Lemoult, Stephanie C.,Richardson, Paul F.,Roberts, Stanley M.
-
-
- Oxidation of Diols with Sodium Bromite Trihydrate in Organic Solvents in the Presence of Alumina
-
The title oxidation of diols with two primary hydroxy groups (symmetrical diols) and those with both a primary and a secondary hydroxy group (unsymmetrical diols) gives the corresponding lactones or the hydroxy ketones, being dependent upon the types of diols.
- Morimoto, Takashi,Hirano, Masao,Iwasaki, Keiko,Ishikawa, Takashi
-
-
- Process for the production of isosolanone and solanone, intermediates useful in said process and organoleptic uses of said intermediates
-
Described is a novel genus of compounds defined according to the structure: STR1 wherein Z represents hydrogen, MgX and the moiety having the structure: STR2 and X represents chlor, bromo, or iodo; as well as 5-isopropyl-8-methyl-5,8-nonadien-2-one; uses of same as intermediates in a process for producing isosolanone and solanone; and organoleptic uses of 5-isopropyl-8-methyl-5,8-nonadien-2-one and 2,6-dimethyl-5-methylene-1-hepten-4-ol. The novel process of our invention involved the steps of: (i) formation of the compound having the structure: STR3 by means of reacting 3-methyl-2-methylenebutanal with the compound having the structure: STR4 (ii) acid hydrolysis of the resulting compound in order to form 2,6-dimethyl-5-methylene-1-heptene-4-ol; (iii) reaction of 2,6-dimethyl-5-methylene-1-hepten-4-ol with methyl aceto acetate in order to form 2,6-dimethyl-5-methylene-1-hepten-4-yl aceto acetate or, directly, 5-isopropyl-8-methyl-5,8-nonadiene-2-one; (iv) reacting 2,6-dimethyl-5-methylene-1-hepten-4-yl aceto acetate in the presence of an appropriate catalyst to form the 5-isopropyl-8-methyl-5,8-nonadiene-2-one; and (v) isomerizing the 5-isopropyl-8-methyl-5,8-nonadien-2-one in order to form a mixture of solanone and the isosolanone or 5-isopropyl-8-methyl-5,8-nonadiene-2-one.
- -
-
-