Methyl groups, chiral

The amino acid methionine is formed by a melhylation reaction of homo cysteine with iV-methyltetrahydrofolate. The stereochemistry of the reactior has been probed by carrying out the transformation using a donor with a "chiral methyl group" that contains protium (H), deuterium (D), and tritium (T isotopes of hydrogen. Does the methylation reaction occur with inversion oi retention of configuration ... 

If a chiral group is generated in the system to be studied, then chirality analysis of that group typically entails the removal of that moiety in a defined set of reactions such that the stereochemistry is not altered or the reactions have a known stereochemical course. For example, chirality analysis of chiral methyl groups typically involves conversion of the methyl groups into acetic acid. 

Chiral Methyl or Methylene Groups. Upon following a specific set of reactions, utilizing isotopically labeled reagents, chiral methylene groups (e.g., R-CHD—RO ) or chiral methyl groups (e.g., R—CHDT) can be substituted or incorporated into substrates. With such labeled compounds, stereochemical issues not apparent with the unlabeled substrate can be readily addressed. ... 

This procedure involves the enzymatic conversion of the chiral acetate (C(HDT)COO ), obtained from experiments involving chiral methyl groups, to labeled malate. The enzymes used in this procedure include acetate kinase, phosphotransacetylase, malate synthase, and fumarase. 

A method for the determination of carbon-linked methyl groups (and, by extension, used in the analysis of chiral methyl groups in stereochemical studies of enzyme-catalyzed reactions acting on methyl groups). In this procedure, the methyl groups are converted to acetic acid by oxidation of the metabolite with chromic and sulfuric acids. Milder versions are also available. 

STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS CHIRAL METHYL GROUPS Chiral purity,... 

For reviews of compounds where chirality is due to the presence of deuterium or tritium, see Barth Djcrassi Tetrahedron 1981, 24, 4123-4142 Arigoni Eliel Top. Stereochem. 1969, 4, 127-243 Verbit Prog. Phys. Org. Chem. 1970,7,51-127. For a review of compounds containing chiral methyl groups, see Floss Tsai Woodard Top. Stereochem. 1984, 75, 253-321. 

A second example is isomerization of isopentenyl diphosphate to dimethylallyl diphosphate (Eq. 13-56) 304-307 The stereochemistry has been investigated using the 3H-labeled compound shown in Eq. 13-56. The pro-R proton is lost from C-2 and a proton is added to the re face at C-4. When the reaction was carried out in 2H20 a chiral methyl group was produced as shown.304 A concerted proton addition and abstraction is also possible, the observed trans stereochemistry being expected for such a mechanism. However, the... 

When pyruvate with a chiral methyl group is carboxylated by pyruvate carboxylase the configuration at C-3 is retained. The carboxyl enters from the 2-si side, the same side from which the proton (marked H ) was removed to form the enolate anion (Eq. 14-12). Comparable stereochemistry has been established for other biotin-dependent enzymes.64 65... 

The fundamental difference between generating a chiral methyl group from a methylene group and converting a chiral methyl group into methylene... 

Identify both pericyclic steps used in the synthesis 6.32 —> 6.33 of a chiral methyl group, and show that they obey the Woodward-Hoffmann rule. 

A second type of reaction whose stereochemistry was elucidated by the use of chiral methyl groups is of the CDTXY->CHDTX type, exemplified by the citrate lyase reaction (Fig. 69). The stereochemical outcome of a number of these reactions has also been tabulated 149). 

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