Stereochemical probes

The usually tedious work of synthetizing the stereochemical probes is rewarded in most cases by information that is not obtainable by other means. However, the mechanistic interpretation of the results may not be simple as the data are sometimes obscured by side reactions, interconversion of isomers, and the multistep character of catalytic reactions. 

Stereochemical probes of the specificity of substrates, products, and effectors in enzyme-catalyzed reactions, receptor-ligand interactions, nucleic acid-ligand interactions, etc. Most chirality probe studies attempt to address the stereospecificity of the substrates or ligands or even allosteric effectors. However, upon use of specific kinetic probes, isotopic labeling of achiral centers, chronfium-or cobalt-nucleotide complexes, etc., other stereospecific characteristics can be identified, aU of which will assist in the delineation of the kinetic mechanism as well as the active-site topology. A few examples of chirality probes include ... 

The results from the preceding section suggest that the 1,2 vs. 1,4 competition is quite complex and a better understanding of the fundamental processes (role of the counter-ion, of the solvent, factors controlling the addition step. ..) is a necessary prerequisite for a detailed analysis. We therefore turned to the study of nucleophilic additions to chiral saturated carbonyls, using the asymmetric induction as a stereochemical probe. 

Adam and coworkers have carried out several studies aimed at elucidating the geometry of the transition-state structure for the allylic alcohol epoxidation using chiral substrates as stereochemical probe (equation 38). The threo.erythro diasteroselec-tivities for the epoxidation of a set of methyl-substituted chiral allylic alcohols with A ... 

Methyltrioxorhenium-based oxidants, i.e. MT0/H202, MT0/H202/substituted pyri-dines and MTO/UHP , are active in the epoxidation of many double-bond typologies, including allylic alcohols. Regiochemical and stereochemical probes have been... 

Stereochemical probes of intramolecular H-abstraction leads to a conclusion not in contradiction with the II electronic configuration and also reveals that simple amidyl radicals react exclusively as the N-radical but not the 0-radical (25). Scarcity of data in this area does not allow a definitive discussion on stereochemical controls of amidyl radical reactions that are being studied in our group. 

Scheme 2.2.5.11 Preparation of a fluorescent stereochemical probe useful for transaldolase screening.

Martell and Calvin588 have summarized the pioneering studies of Mann and Pope, using tap (36) as a stereochemical probe in Pt11 chemistry and ML3+ (M = Co, Rh L = tap) have been prepared.583,584 The other tripodal ligands have been used more frequently in stability constant studies and the results have been reviewed.589,590... 

Addition to formaldehyde [378] and other aldehydes [379,380] proceeds with high absolute stereoselectivity for the (5f )-configurated products (configurational reference changes for any substrate larger than formaldehyde ). In contrast, no or only a low level of relative acceptor diastereoselectivity at the chiral C-6 was determined in the reactions with acetaldehyde (6S/6R 1 1) [379] and propionaldehyde (130/131 = 1 2.4) [380] as the stereochemical probes. 

The values in Table II were obtained by analysis of the A3A 3 XX spin system observed in the 2 P and spectra, using F F homonuclear INDOR experiments. The dispersion in the J(PP) values is probably due to a more important contribution of the txa.n conformation to the conformational populations in the B1C40 and d,t isomers. The 2J(PCF3) values show also marked differences between the m 60 and the d,Z isomer but they will be difficult to use as a stereochemical probe as long as there is no reliable way to identify these isomers. 

Me3M+ cations (M = C, Si, Ge, Sn) were used as a stereochemical probe in gas-phase reactions with 1,2-cyclopentanediol isomers98. The decomposition pattern of the [1,2-cyclopentanediol + Me3M]+ adducts depended on the stereochemistry of the diol. For c/.v-diol the decomposition led readily to hydrated [Me3M(OH2)]+ cations, while for frans-diol the adduct was significantly more stable the Me3Ge+ cation was a more sensitive and selective reactant than other group 14 cations. 

Most common for the synthetic practitioner are inhibition studies or probe reactions making use of typical competitive radical reactions with known rate constants. Stereochemical probe studies pointing to the involvement of planar radical intermediates are also valuable. An approximate lifetime of radicals can in principal be estimated from such reactions. 

The elucidation of reaction mechanisms is a central topic in organic chemistry that led to many elegant studies emphasizing the interplay of theory and experiment as demonstrated, for example, by the seminal contributions of the Houk group to the understanding of the Diels-Alder and other pericyclic reactions.38 This reaction class is rather typical for the elucidation of reaction mechanisms. On the experimental side, the toolbox of solvent, substituent and isotope effect studies as well as stereochemical probes have been used extensively, while the reactants, products, intermediates and transition structures involved have been calculated at all feasible levels of theory. As a result, these reactions often serve as a success story in physical organic chemistry. 

G., Schuermann, M., Sprenger, G.A., Fessner, W.D. and Reymond, J.L. (2003) Fluorogenic stereochemical probes for transaldolases. Chemistry-A European Journal, 9, 893-899. 

The transient spectra of C6o at Amax = 1080 nm formed in photoinduced electron transfer from Danishefsky s diene to Cso have been detected, accompanied by the decay of Ceo in a laser flash photolysis of the reaction system [305]. The observed rate constant agrees well with the predicted rate constant on the basis of an electron transfer mechanism shown in Scheme 11 [305], In the photochemical Diels-Alder reaction of Cgo, a stereochemicaUy defined (l , 3Z)-l,4-disubstituted Danishefsky s diene is used as a stereochemical probe. In the photochemical Diels-... 

This initial survey of naturally occurring cyclopropanoid metabolites raises several questions relating to the biochemistry including function and metabolism of the compounds and in particular the cyclopropyl group. In the bulk of this chapter we summarize what evidence is available on modes of biosynthesis and degradation of cyclopropyl substituents. While in several cases, e.g. in terpenoids and steroids of the cycloartenol (20) case, biogenetic tracer studies or stereochemical probes have been carried out and are quite revealing about precursor-product relationships, there are very few cases indeed where specific enzymatic catalysts have been identified, isolated, and characterized for action on specific cyclopropane substrates. 

The work described herein deals mainly with recent experiments aimed at evaluating FAB as a stereochemical probe. As it is shown in Section II, no definitive methods or rules are available in mass spectrometry for such analysis, although several reports indicate that it should be possible to make such use of this physical method. This is due to the relatively small amount of data available on FAB. Consequently, we will present several original data that we obtained in our laboratories and that are unpublished as yet. 

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