Stereochemical Course Of Reaction Research Articles

A Silicon-Stereogenic Silanol - 18 O-Isotope Labeling and Stereogenic Probe Reveals Hidden Stereospecific Water Exchange Reaction.

A silicon-stereogenic aminosilanol was isolated in excellent diastereomeric ratio and the absolute configuration was determined. The silanol is configurative and condensation stable in solution and shows stereoselective transformations with a clean stereospecific pathway in follow-up reactions, which leads to the isolation of a silicon-stereogenic zinc complex and siloxane compounds. Investigations with 18 O-labelled water and mass spectrometry analysis revealed an otherwise hidden exchange of oxygen atoms of silanol and water in solution that proceeds with retention of the configuration at the silicon center. This novel combination of a stereochemical probe and isotopic labeling in a silicon-stereogenic compound opens new analytic possibilities to study stereochemical courses of reactions with the aid of chiral silanols mechanistically.

Stereochemical Course of the Reaction Catalyzed by RimO, a Radical SAM Methylthiotransferase.

RimO is a member of the growing radical S-adenosylmethionine (SAM) superfamily of enzymes, which use a reduced [4Fe-4S] cluster to effect reductive cleavage of the 5' C-S bond of SAM to form a 5'-deoxyadenosyl 5'-radical (5'-dA(•)) intermediate. RimO uses this potent oxidant to catalyze the attachment of a methylthio group (-SCH3) to C3 of aspartate 89 of protein S12, one of 21 proteins that compose the 30S subunit of the bacterial ribosome. However, the exact mechanism by which this transformation takes place has remained elusive. Herein, we describe the stereochemical course of the RimO reaction. Using peptide mimics of the S12 protein bearing deuterium at the 3 pro-R or 3 pro-S positions of the target aspartyl residue, we show that RimO from Bacteroides thetaiotaomicron (Bt) catalyzes abstraction of the pro-S hydrogen atom, as evidenced by the transfer of deuterium into 5'-deoxyadenosine (5'-dAH). The observed kinetic isotope effect on H atom versus D atom abstraction is ∼1.9, suggesting that this step is at least partially rate determining. We also demonstrate that Bt RimO can utilize the flavodoxin/flavodoxin oxidoreductase/NADPH reducing system from Escherichia coli as a source of requisite electrons. Use of this in vivo reducing system decreases, but does not eliminate, formation of 5'-dAH in excess of methylthiolated product.

Examining the role of phosphate in glycosyl transfer reactions of Cellulomonas uda cellobiose phosphorylase using d-glucal as donor substrate

Cellobiose phosphorylase from Cellulomonas uda (CuCPase) is shown to utilize d-glucal as slow alternative donor substrate for stereospecific glycosyl transfer to inorganic phosphate, giving 2-deoxy-α-d-glucose 1-phosphate as the product. When performed in D2O, enzymatic phosphorolysis of d-glucal proceeds with incorporation of deuterium in equatorial position at C-2, implying a stereochemical course of reaction where substrate becomes protonated from below its six-membered ring through stereoselective re side attack at C-2. The proposed catalytic mechanism, which is supported by results of docking studies, involves direct protonation of d-glucal by the enzyme-bound phosphate, which then performs nucleophilic attack on the reactive C-1 of donor substrate. When offered d-glucose next to d-glucal and phosphate, CuCPase produces 2-deoxy-β-d-glucosyl-(1→4)-d-glucose and 2-deoxy-α-d-glucose 1-phosphate in a ratio governed by mass action of the two acceptor substrates present. Enzymatic synthesis of 2-deoxy-β-d-glucosyl-(1→4)-d-glucose is effectively promoted by catalytic concentrations of phosphate, suggesting that catalytic reaction proceeds through a quaternary complex of CuCPase, d-glucal, phosphate, and d-glucose. Conversion of d-glucal and phosphate presents a convenient single-step synthesis of 2-deoxy-α-d-glucose 1-phosphate that is difficult to prepare chemically.

Synthesis and antimicrobial evaluation of novel benzo[b]thiophenes comprising β-lactam nucleus

Synthesis, structural characterization, and biological activity studies of benzo[b]thiophene derivatives containing β-lactam nucleus are described. Cycloaddition of azomethines (4a–j) to in situ-generated ketenes from 2,4-dichlorophenoxyacetic acid, in the presence of triethylamine and benzenesulfonyl chloride afforded the title compounds (5a–j). The stereochemical course of reaction depends on both the substituents on the ketenes as well as on the imines. The mechanism for the formation of cis/trans derivative is presented.

In vitro Characterization of Enzymes Involved in the Synthesis of Nonproteinogenic Residue (2S,3S)‐β‐Methylphenylalanine in Glycopeptide Antibiotic Mannopeptimycin

Mannopeptimycin, a potent drug lead, has superior activity against difficult-to-treat multidrug-resistant Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). (2S,3S)-beta-Methylphenylalanine is a residue in the cyclic hexapeptide core of mannopeptimycin, but the synthesis of this residue is far from clear. We report here on the reaction order and the stereochemical course of reaction in the formation of (2S,3S)-beta-methylphenylalanine. The reaction is executed by the enzymes MppJ and TyrB, an S-adenosyl methionine (SAM)-dependent methyltransferase and an (S)-aromatic-amino-acid aminotransferase, respectively. Phenylpyruvic acid is methylated by MppJ at its benzylic position at the expense of one equivalent of SAM. The resulting beta-methyl phenylpyruvic acid is then converted to (2S,3S)-beta-methylphenylalanine by TyrB. MppJ was further determined to be regioselective and stereoselective in its catalysis of the formation of (3S)-beta-methylphenylpyruvic acid. The binding constant (K(D)) of MppJ versus SAM is 26 microM. The kinetic constants with respect to k(cat Ppy) and K(M Ppy), and k(cat SAM) and K(M SAM) are 0.8 s(-1) and 2.5 mM, and 8.15 s(-1) and 0.014 mM, respectively. These results suggest SAM has higher binding affinity for MppJ than Ppy, and the C--C bond formation in betamPpy might be the rate-limiting step, as opposed to the C--S bond breakage in SAM.

Stereoelectronic Effects in Diastereoselective Formation of Fulleroids

The substituent effects on diastereoselective formation of fulleroids in the reactions of C(60) with various unsymmetrical diazoalkanes were investigated. The steric demand on the stereochemical course of reactions dominated the diastereoselectivity for diazoalkanes bearing aliphatic as well as monosubstituted pi-resonating groups, whereas the stereoelectronic effects of coexisting pi-resonating aromatic and cyclopropyl groups played a crucial role in the ring closure of the radical intermediates, overriding the steric demand.

Stereochemical Studies on the Making and Unmaking of Isopentenyl Diphosphate in Different Biological Systems

To investigate the unknown stereochemical course of the reaction catalyzed by the type-II isomerase, which interconverts isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), a sample of [1,2-(13)C2]-IPP stereospecifically labelled with 2H at C2 was prepared by incubating a D2O solution of (E)-4-hydroxy-3-methyl[1,2-(13)C2]but-2-enyl diphosphate with a recombinant IspH protein of Escherichia coli in the presence of NADH as a reducing agent and flavodoxin as well as flavodoxin reductase as auxiliary proteins. As monitored by 13C-NMR spectroscopy, treatment of the deuterated IPP with either type-I or type-II IPP isomerase resulted in the formation of DMAPP molecules retaining all the 2H label of the starting material. From the known stereochemical course of the type-I isomerase-catalyzed reaction, one has to conclude that the label introduced from D2O in the course of the IspH reaction resides specifically in the H(Si)-C2 position of IPP and that the two isomerases mobilize specifically the same H(Re)-C2 ligand of their common IPP substrate. The outcome of an additional experiment, in which unlabelled IPP was incubated in D2O with the type-II enzyme, demonstrates that the two isomerases also share the same preference in selecting for their reaction the (E)-methyl group of DMAPP.

Evolution of Function in the Crotonase Superfamily: The Stereochemical Course of the Reaction Catalyzed by 2-Ketocyclohexanecarboxyl-CoA Hydrolase

Members of the mechanistically diverse enoyl-CoA hydratase (crotonase) superfamily catalyze reactions that involve stabilization of an enolate anion derived from an acyl thioester of coenzyme A. 2-Ketocyclohexanecarboxyl-CoA hydrolase (BadI), found in a pathway for anaerobic degradation of benzoate by Rhodopseudomonas palustris, is a member of the crotonase superfamily that catalyzes a reverse Dieckmann reaction in which the substrate is hydrolyzed to pimelyl-CoA. The substrate is the configurationally labile 2S-ketocyclohexanecarboxyl-CoA, and in 2H2O solvent hydrogen is incorporated into the 2-proS position of the pimelyl-CoA product. Therefore, the stereochemical course of the BadI-catalyzed reaction is inversion. This information is important for understanding the roles of active-site functional groups in the active site of BadI as well as in the active sites of the homologous 1,4-dihydroxynaphthoyl-CoA synthases that catalyze a forward Dieckmann reaction.

ChemInform Abstract: Highly Enantioselective Syntheses of anti Homoaldol Products by (-)-Sparteine-Mediated Lithiation/Transmetalation/Substitution of N-Boc Allylic Amines.

(−)-Sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines provides anti-configured homoaldol precursors in yields of 38−85% and enantiomeric ratios of 83:17−99:1. Subsequent O-protection and hydrolysis allows access to O-protected homoaldol adducts in good yields. The absolute configurations of the homoaldol products have been assigned by calculation of optical rotations and by X-ray crystallography of derivatives. A stereochemical course of reaction for the lithiation/transmetalation/substitution sequence is proposed.

Highly enantioselective syntheses of anti homoaldol products by (-)-sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines.

[reaction: see text](-)-Sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines provides anti-configured homoaldol precursors in yields of 38-85% and enantiomeric ratios of 83:17-99:1. Subsequent O-protection and hydrolysis allows access to O-protected homoaldol adducts in good yields. The absolute configurations of the homoaldol products have been assigned by calculation of optical rotations and by X-ray crystallography of derivatives. A stereochemical course of reaction for the lithiation/transmetalation/substitution sequence is proposed.

Linking Diversity in Evolutionary Origin and Stereospecificity for Enoyl Thioester Reductases: Determination and Interpretation of the Novel Stereochemical Course of Reaction Catalyzed by Crotonyl CoA Reductase fromStreptomyces collinus

The stereochemical course of reduction of crotonyl CoA by the novel crotonyl CoA reductase (CCR) of Streptomyces collinus was determined using a radiochemical assay. The reaction was shown to proceed with transfer of the hydrogen from the pro-4S position of NADPH to the Re face of the β-carbon of crotonyl CoA. This transfer represents the first exception to the observation that enoyl thioester reductases catalyze transfer of the pro-4S hydrogen of NADPH to the Si face of the substrate. The observation of addition of solvent hydrogen to the Re face of the α-carbon in the reaction catalyzed by CCR demonstrated that the overall reduction of crotonyl CoA proceeds in an anti fashion. The overall stereochemical outcome of the reaction catalyzed by CCR is different to the four stereochemical outcomes that have previously been observed for enoyl thioester reductases. It is significant that the predicted amino acid sequence of CCR has also been shown to be unrelated to other enoyl thioester reductases. Based on th...

Stereochemistry of coordination compounds

Survey of Methods for the Elucidation of the Stereochemistry of Coordination Compounds. Theoretical Bases for the Coordination Geometries of Metal Ions. General Concepts in Topographic Stereochemistry of Coordination Compounds. Topographical Stereochemistry of Mononuclear Coordination Units. Topographical Stereochemistry of Polynuclear Coordination Units. The Stereochemical Course of Reactions of Metal Complexes. Appendices. Index.

Nonreductive Enantioselective Ring Opening of N‐(Methylsulfonyl)dicarboximides with Diisopropoxytitanium α,α,α′,α′‐Tetraaryl‐1,3‐dioxolane‐4,5‐dimethanolate

AbstractThe bicyclic and tricyclic meso‐N‐(methylsulfonyl)dicarboximides 1a–f are converted enantioselectively to isopropyl [(sulfonamido)carbonyl]‐carboxylates 2a–f by diisopropoxytitanium TADDOLate (75–92% yield; see Scheme 3). The enantiomer ratios of the products are between 86:14 and 97:3, and recrystallization from CH2Cl2/hexane leads to enantiomerically pure sulfonamido esters 2 (Scheme 3). The enantioselectivity shows a linear relationship with the enantiomer excess of the TADDOL employed (Fig.3). Reduction of the ester and carboxamide groups (LiAlH4) and additional reductive cleavage of the sulfonamido group (Red‐Al) in the products 2 of imide‐ring opening gives hydroxy‐sulfonamides 3 and amino alcohols 4, respectively (Scheme 4). The absolute configuration of the sulfonamido esters 2 is determined by chemical correlation (with 2a,b; Scheme 6), by the X‐ray analysis of the camphanate of 3e (Fig. 1), and by comparative 19F‐NMR analysis of the Mosher esters of the hydroxy‐sulfonamides 3 (Table 1). A general proposal for the assignment of the absolute configuration of primary alcohols and amines of Formula HXCH2CHR1R2, X = O, NH, is suggested (see 11 in Table 1). It follows from the assignment of configuration of 2 that the Re carbonyl group of the original imide 1 is converted to an isopropyl ester group. This result is compatible with a rule previously put forward for the stereochemical course of reactions involving titanium TADDOLate activated chelating electrophiles (12 in Scheme 7). A tentative mechanistic model is proposed (13 and 14 in Scheme 7).

Evidence for distinct mechanisms of monocyclic β-lactam biosynthesis

The hydroxymethylene oxidation state of primary metabolic precursors is maintained in the biosynthesis of the β-lactam ring of proclavaminic acid as it is in nocardicin A, but the net stereochemical course of reactions to give the azetidinone N–C-4 bond is the opposite.

The stereochemical course of reactions catalysed by the cellobiohydrolases produced by Talaromyces emersonii.

Three forms of exocellobiohydrolase (EC 3.2.1.91), CBH IA, CBH IB and CBH II, were isolated to apparent homogeneity from culture filtrates of the aerobic fungus Talaromyces emersonii. CBH IA and CBH II appear to be native forms of these enzymes, while CBH IB may represent a proteolytic degradation product of the CBH IA enzyme. The hydrolysis of beta-cellobiosyl fluoride by each form was monitored by 1H-n.m.r. spectroscopy. The reactions catalysed by CBH IA and CBH IB proceed with retention of the anomeric configuration, whereas that catalysed by CBH II is one of inversion. Thus one may deduce that CBH IA (or CBH IB) and CBH II operate double and single displacement reactions respectively during catalysis of substrate. On the basis of these findings and the observed substrate specificities of the various forms, one may conclude that CBH IA (and CBH IB) is a family C enzyme, while CBH II belongs to family B [Henrissat, Claeyssens, Tomme, Lemesle & Mornon (1989) Gene 81, 83-95].

The stereochemical course of reactions catalysed by Escherichia coli glutamic acid decarboxylase

Esherischia coli glutamic acid decrboxylase reprotonates the quinoid intermediate derived from (2S)-glutamic acid on the 4′-Si-face of the coenzyme in an abortive transamination reaction, intorduces the 3-pro-R hydrogen of β-alanine during the decarboxylation of (2S)-aspartic acid and removes the 1-pro-R hydrogen of N4′-(2-phosphoethyl)-pyridoxamine 5′-phosphate in a reactivation reaction; the results indicate that the distal binding groups of substrates and inhibitors occupy similar positions at the active site on the 3′-phenolic group side of the coenzyme.

Allylstannation: X. Stereochemical course of the addition reactions of ( E/Z-Bu 3SnCH 2CHCHCH 3 with aldehydes in the presence of Lewis acids (Bu 2SnCl 2, BF 3·Et 2O, and TiCl 4)

Reactions between ( E/Z)-Bu 3SnCH 2CHCHCH 3 and RCHO (R  CH 3, C 2H 5, n-C 3H 7, n-C 4H 9, n-C 5H 11, (CH 3) 2CH, (CH 3) 3C, C 6H 5, CH 2CH, CH 2C(CH 3), ( E)-CH 3CHCH, ( E)-C 3H 7CHCH, ( E)-C 6H 5CHCH) have been carried out in the presence of Lewis acids such as Bu 2SnCl 2, BF 3·Et 2O and TiCl 4. The stereochemical course of the reactions to give homoallylic alcohols does not necessarily depend on the formation of intermediate Lewis acid-aldehyde complexes, but rather upon the formation of allylmetal compounds (e.g., Bu 2ClSnCH 2CHCHCH 3, Bu 2ClSnCH(CH 3)CHCH 2, Cl 3TiCH 2CHCHCH 3, etc.) which are the actual species which react with the carbonyl compounds. Bu 3SnCH 2CHCHCH 3 does not undergo the reaction.

Enzyme inhibition by electrophilic cyclopropane derivatives

Electrophilic cyclopropane-containing compounds have been found in our previous studies to be latent, irreversible inhibitors of horse liver alcohol dehydrogenase, lactate dehydrogenase, and carboxypeptidase A. In addition, cyclopropyl methanols have provided information concerning the mechanism of hydrogen transfer by nicotinamide coenzymes and dehydrogenases. These results are evaluated with the aid of molecular graphics and frontier orbital considerations in the light of the established stereochemical courses of reactions involving cyclopropane ring opening. It is concluded that mechanisms for nucleophilic inhibition consistent with chemical theory and precedent are available at each enzyme's active site. Potential enzymic nucleophiles are identifed.

Substrate metal-adenosine 5'-triphosphate chelate structure and stereochemical course of reaction catalyzed by the adenosine triphosphatase from the thermophilic bacterium PS3

Substrate metal-adenosine 5'-triphosphate chelate structure and stereochemical course of reaction catalyzed by the adenosine triphosphatase from the thermophilic bacterium PS3

The stereochemical course of amino acid activation by methionyl- and tyrosyl-tRNA synthetases

Stereochemical analysis has long been recognised as a powerful tool for elucidating the mechanisms of chemical and enzyme-catalysed reactions. Although much is known about the stereochemical course of reactions at saturated carbon, phosphate and thiophosphate esters whose ligands to phosphorus are also tetrahedrally disposed, are capable in principle of revealing sterochemical information about events at the active site of enzymes that transform such substrates. Nucleotidyl transferases are a group of enzymes which in general selectively use one of the diastereoisomers of a nucleoside 5'(1-thiotriphosphate), such as isomers A and B of adenosine 5'(1-thiotriphosphate), designated ATP alpha S-A and ATP alpha S-B, and allow investigation of the stereochemical course of nucleotidyl transfer. We have developed a simple method based on 31P nuclear magnetic resonance spectroscopy for determining the stereochemical course of these reactions, and using this method show here that the nucleotidyl transfer step in two aminoacyl-tRNA synthetases from Escherichia coli occurs with inversion of configuration at phosphorus. These observations greatly constrain the mechanistic possibilities for these enzymes, and are interpreted most simply as a direct 'in line' transfer from ATP to the amino acid.