Chirality label

Kwakman et al. [65] described the synthesis of a new dansyl derivative for carboxylic acids. The label, N- (bromoacetyl)-A -[5-(dimethylamino)naphthalene-l-sulfonyl]-piperazine, reacted with both aliphatic and aromatic carboxylic acids in less than 30 min. Excess reagent was converted to a relatively polar compound and subsequently separated from the derivatives on a silica cartridge. A separation of carboxylic acid enantiomers was performed after labeling with either of three chiral labels and the applicability of the method was demonstrated by determinations of racemic ibuprofen in rat plasma and human urine [66], Other examples of labels used to derivatize carboxylic acids are 3-aminoperylene [67], various coumarin compounds [68], 9-anthracenemethanol [69], 6,7-dimethoxy-l-methyl-2(lH)-quinoxalinone-3-propionylcarboxylic acid hydrazide (quinoxalinone) [70], and a quinolizinocoumarin derivative termed Lumarin 4 [71],... 

Racemization of chiral a-methyl benzyl cation/methanol adducts. The rate of exchange between water and the chiral labeled alcohols as a function of racemization has been extensively used as a criterion for discriminating the Sn2 from the SnI solvolytic mechanisms in solution. The expected ratio of exchange vs. racemization rate is 0.5 for the Sn2 mechanism and 1.0 for a pure SnI process. With chiral 0-enriched 1-phenylethanol in aqueous acids, this ratio is found to be equal to 0.84 0.05. This value has been interpreted in terms of the kinetic pattern of Scheme 22 involving the reversible dissociation of the oxonium ion (5 )-40 (XOH = H2 0) to the chiral intimate ion-dipole pair (5 )-41 k-i > In (5 )-41, the leaving H2 0 molecule does not equilibrate immediately with the solvent (i.e., H2 0), but remains closely associated with the ion. This means that A inv is of the same order of magnitude of In contrast, the rate constant ratio of... 

There is evidence (but not conclusive evidence) that the mechanisms involves direct phosphoryl transfer to water rather than the formation of a phosphoenzyme intermediate.293 This utilizes the fact that ATP also serves as a substrate to inorganic pyrophosphatase. Hydrolysis of the ATP analogue adenosine 5 -0-(3-thiotriphosphate) chirally labelled with I70 and I80 at the y-phosphate proceeds with inversion of configuration to give the chiral [170,180]-thiophosphate (Figure 13).293... 

A large number of compounds has now been prepared in which chirality arises as a result of the presence of =CH2H or =CH3H. A few of them, which have been of particular importance, will be considered here to indicate some of the experimental strategies which have been used. More extensive general information is available [10,11], and Parry [86] has discussed chirally labeled a-amino acids. 

In the achiral species 19, 20 and 21 the (R)- and (S)-1,2-propanediol binding modes are equivalent and no preferred retention or loss of the heavy oxygen isotope should be expected, even upon stereospedfic migration. This has been confirmed experimentally, i.e., about 50% of the 18O was retained in all three cases. In the chiral specimens 22, 23, 24 and 25, however, stereospecific migration of the unlabelled hydroxyl group should lead to chirally labelled geminal diols. Such a process should be preferred by the substrates 23 and 25 (Fig. 18). 

The CHEMiCAL ABSTRACTS stereochemical notation system is composed of four parts the site symmetry term, the configuration number, the chirality label, and the ligand stereochemical label. 

Three different chirality labels are used to indicate the chirality at the coordination center. Although these symbols... 

In a system Xaaaa the a groups are, of course, also homotopic and thus indistinguishable. By the same formalism used above such a center can be called proproprochiral, because it is three substitution steps removed from a chiral center. Hence, three isotopic and/or heteroatomic replacements are required in order to study the steric course of reactions at such a center. The only chiral version of a proproprochiral center synthesized to date is an inorganic phosphate molecule carrying one heteroatomic and two isotopic replacements, (R)- and (S)-[I60,170,180]phosphorothioate. The presence of the sulfur heteroatom, of course, gives this chirally labeled species the properties of a proprochiral center with the concomitant simplification in the analytical methodology required to distinguish an R from an S isomer. 

The general approach in elucidating the stereochemical course of an enzyme-catalyzed reaction involves the following steps (i) synthesis of substrates chirally labeled (with 170, 180, or S) at phosphorus (ii) use of chirally labeled substrates to perform the reaction and isolate the product and (iii) determination of the absolute or relative configuration of the substrate and the product. 

Unlike a chiral methyl group, in which the tritium is isotopically dilute, a chiral phosphoryl group can be obtained with >50% purity ( purity is defined as the percentage of the chirally labeled species, i.e., the M + 3 species) and with >95% chirality ( chirality is defined as the optical purity of the chirally labeled species) (119). Therefore it is not impractical to ask whether the chiroptical properties of a chiral phosphoryl group can be observed. Cullis and Lowe (23) have reported a CD curve of methyl [( )- 6 O,17 O,18 0] phosphate with a maximum at 208 nm (Ae = 2.7 X 10-3). Although this is a direct way to measure the chirality of a phosphoryl group, it would be useful only in compounds which do not contain any other chiral centers. Furthermore, the CD curve of only one enantiomer of the above compound has been reported. Results based on CD should be evaluated with reservation until they can be confirmed with the opposite isomer. 

Whereas the 0 effect on P NMR chemical shifts is sufficient for determining the configurations of chirally labeled samples of prochiral phosphorus atoms in a diastereomeric environment, additional use of the quadrupolar effect of O on P NMR resonances is required for configurational analyses of oxygen chiral phosphate monoesters. The basic strategy for the configurational analyses of phosphate monoesters is the same, i.e., the enantiomeric center in the monoester must be converted to a diastereomeric center in a cyclic phosphodiester so that... 

Since these early studies, numerous additional procedures have been developed for the synthesis of chiral labeled acetic acid and other chiral labeled molecules by chemical (I41-15I) and enzymic methods 152-155). The malate synthase/fumarase system described above continues to be the most widely used method for the stereochemical analysis of chiral labeled acetic acid resulting from the degradation of product molecules containing chiral methyl groups. 

When H, = H, H, = H and H = H when H, = H, H, = H and Hi, = H. The (35)-[3- H,2H]- and (3S)-[3-3H, H]oxaloacetates were enzymically synthesized from stereospecifically labeled samples of aspartate using glutamate-oxaloacetaie transaminase. Configurational analysis of the samples of [ H, H H] pyruvate involved enzymic conversion to chiral labeled acetate (lactate dehydrogenase/lactate oxidase), and the sequential use of malate synthase and fiimarase (see text) (223). 

The validity of the above scheme was further explored with cadaverine samples chirally labelled with tritium at C-1. (The samples were obtained by decarboxylation of L-lysine mediated by L-lysinedecarboxylase from Bacillus cadaveris. The absolute configuration of the two materials is unknown and they were accordingly named [L4- H]- and [15- H]-cadaverine.) The labelling pattern of the derived N-methylpelletierine (22) was in accord with stereospecific oxidative deamination to A -piperideine (30) and in agreement with the proposed model. Both cadaverine samples afforded iV-methylpelletierine (22) with a label at C-6 but only [l/4- H]cadaverine labelled C-2. (The puzzling loss of 25% of the tritium from non-chirally labelled [l- C,l- H]cadaverine on incorporation into N-methylpelletierine is now explained in terms of this model, the tritium loss being exactly as predicted. It seems that subsequent elaboration of N-methylpelletierine (22) to pseudopelletierine (24) is accompanied by preferential tritium retention at C-6 by a primary isotope effect. )... 

This study with the chirally labelled cadaverines brings to light an apparent anomaly. Decarboxylation of L-[2- H]lysine by the enzyme from B. cadaveris affords [lB- H]cadaverine. When this material is converted into N-methyl-pelletierine (22) and AT-methylallosedridine in S. sarmentosum the tritium destined for C-2 is lost. On the other hand conversion of lysine into the sedamine in S. acre results in the retention of tritium originally present at C-l The simplest explanation of this is that the protonation of (28) in the micro-organism and the plants proceeds with opposite stereochemistry. 

Use of serine hydroxymethyltransferase with [2,2- H2]glycine and or [2,2- H2]glycine and H20 gives (2S)- and (2/ )-[2- H 2- Hj]glycines, respectively, and these were incubated with glycine reductase from Clostridium sticklandii to yield chirally labeled acetates (62) (Scheme 14). These acetates were assayed as described in references 3 and 7 to show that the reduction proceeded with inversion of configuration (62). 

The amino acid homocysteine 148 is obtained on treatment of cystathione 99 with the enzyme / -cystathionase (EC 4.4.1.8). Chang and Walsh (128) used the samples of (4R)- and (4S)-[4- Hi]cystathione 99a, prepared as in Scheme 37, in this reaction and degraded the samples of homocysteine produced to labeled homoserinelactones. This indicated that, as expected, the chirally labeled center was not disturbed in the reaction. 

Echinulin.— The mould metabolite echinulin (126) and its relatives have been the subject of some elegant biosynthetic experiments leading to a clear picture of the way they are elaborated." Echinulin has recently been used as a monitor for the stereochemistry involved in the catabolism of leucine to mevalonic acid " label from the leucine was expected at specific sites in the mevalonate-derived iso-prenoid units of (126). In the event, extensive scrambling of label was observed from the two enantiomers of leucine chirally labelled with "C at C-3. Some selectivity in the labelling was detected, which was interpreted as indicating that carriage of label from leucine to mevalonate had occurred via acetoacetate. 

A number of lanthanide complexes have been shown to exhibit circularly polarized luminescence (CPL—the differential spontaneous emission of left- and right-circularly polarized light). In the absence of any externally applied fields, CPL is exhibited only by systems that have net chirality in their structures or are subject to chiral perturbations by their environment. CPL exhibited by the Af-Af transitions of chiral lanthanide systems provides a sensitive probe of coordination and structure in solution. Applications are limited to systems which possess some element of chirality, but in many cases this merely requires that > 1 ligand of interest has a chiral atom or carries a chiral label (such as a chiral substituent group). ... 

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