Academic literature on the topic 'Crystallography. Carbon compounds. Stereochemistry'

‘The fundamentals’ investigates why the element carbon is so suited for the generation of so many compounds. Carbon has atomic number six, meaning it has six protons in its nucleus and six electrons around the nucleus, four of which are valence electrons held in the outer shell. Carbon achieves a stable, full outer shell of electrons by sharing electrons with other elements and other carbon atoms to form covalent bonds. The carbon–carbon bonds are one of the principle reasons why so many organic molecules are possible, including linear chains, branched chains, and rings. The naming of compounds and identification of structures is also explained along with stereochemistry, functional groups, and intermolecular and intramolecular interactions.

The assignment of secondary alcohols can be carried out by using one of several CDAs [13–15]. The most used and most reliable ones are MPA, 9-AMA, and MTPA [35–40]. Figure 3.1 shows their structures, the correlation models, and a summary of the experimental conditions. MPA and 9-AMA esters share the same conformational composition [37, 39] and only differ in the intensity of their shieldings; therefore both auxiliaries present the same correlation between sign distribution and stereochemistry. MTPA has a different conformational composition and correlation model [38]. As shown in Chapter 1, MPA esters of secondary alcohols and other AMAA esters (e.g., 9-AMA esters) are composed of two sp/ap conformers in fast equilibrium [37, 39]. The sp conformer is more stable than the ap conformer, and this allows the NMR spectrum of an AMAA ester to be interpreted as if it had originated from just the sp form: carbonyl, Cα, and methoxy groups in the auxiliary part and a methine group (Cα′-H) at the alcohol moiety are in the same plane. When we consider this conformation in the (R)- and the (S)-AMAA esters, the L1 group is located under the shielding cone of the aryl in the (R)-AMAA ester, while the L2 is shielded in the (S)-AMAA ester (we strongly recommended that the reader builds Dreiding, or similar, models to assist in visualizing this spatial array). A subtraction defined as the chemical shift in the (R)-AMAA ester minus that in the (S)-AMAA ester results in a negative value for L1 and a positive one for L2 (i.e., negative ΔδRS for L1 and positive ΔδRS for L2). Therefore, for any secondary alcohol derivatized as an AMAA ester, the protons showing a positive ΔδRS sign are located in the tetrahedron around the asymmetric carbon (Cα′) as L2 (at the back) while the protons resulting in a negative ΔδRS take the position of L1.

The nuclear magnetic resonance (NMR) spectra of two enantiomers are identical. Thus, the first step in using NMR to distinguish between two enantiomers should be to produce different spectra that eventually can be associated with their different stereochemistry (i.e., the assignment of their absolute configuration). Therefore, it is necessary to introduce a chiral reagent in the NMR media. There are two ways to address this problem. One is to use a chiral solvent, or a chiral agent, that combines with each enantiomer of the substrate to produce diastereomeric complexes/associations that lead to different spectra. This is the so-called chiral solvating agent (CSA) approach; it will not be further discussed here [33–34]. The second approach is to use a chiral auxiliary reagent [13–15] (i.e., a chiral derivatizing agent; CDA) that bonds to the substrate by a covalent linkage. Thus, in the most general method, the two enantiomers of the auxiliary CDA react separately with the substrate, giving two diastereomeric derivatives whose spectral differences carry information that can be associated with their stereochemistry. The CDA method that employs arylalcoxyacetic acids as auxiliaries is the most frequently used. It can be applied to a number of monofunctionals [14–15] (secondary alcohols [35–43], primary alcohols [44–46], aldehyde [47] and ketone cyanohydrins [48–49], thiols [50–51], primary amines [52–56], and carboxylic acids [57–58]), difunctional [13] (sec/sec-1,2-diols [59–61], sec/sec-1,2-amino alcohols [62], prim/sec-1,2-diols [63–65], prim/sec-1,2-aminoalcohols, and sec/prim-1,2-aminoalcohols [66–68]), and trifunctional (prim/sec/sec-1,2,3-triols [13, 69–70]) chiral compounds. Its scope and limitations are well established, and its theoretical foundations are well known, making it a reliable tool for configurational assignment. Figure 1.1 shows a summary of the steps to be followed for the assignment of absolute configuration of a chiral compound with just one asymmetric carbon and with substituents that, for simplicity, are assumed to resonate as singlets. Step 1 (Figure 1.1a): A substrate of unknown configuration (?) is separately derivatized with the two enantiomers of a chiral auxiliary reagent, (R)-Aux and (S)-Aux, producing two diastereomeric derivatives.

The original coenzymes were small organic molecules that activated enzymes and participated directly in catalyzing enzymatic reactions. Most of them were derived from vitamins and were known as biologically “activated” forms of vitamins such as niacin, riboflavin, thiamine, and pyridoxal. Heme was in a separate category, perhaps because of its widespread biological role as an oxygen carrier, and because it was not a vitamin, it was not widely regarded as a coenzyme. However, heme was clearly an enzymatic prosthetic group in enzymes such as peroxidases and catalase, and it was known to participate in catalysis. Today, heme takes its place among the coenzymes. Other, more recently discovered metallic cofactors round out this chapter on metallocoenzymes. Most of the detailed mechanisms of metallocoenzyme-dependent reactions are not known. Hypothetical mechanisms can often be written, and some of them are supported by a few experiments. Emerging principles are emphasized here for several of the more extensively studied metallocoenzymes. In other cases, the detailed mechanisms that we include in figures and schemes must be regarded as conjectural. We do not regard them as fanciful, but they have not been proved and are referred to as “a mechanism for” in recognition that other possible mechanisms have not been excluded. Space does not permit all conceivable mechanisms to be aired, and we hope that those shown here will stimulate discussion and experimentation. Vitamin B12 coenzymes may be regarded as transitional from traditional coenzymes, in that the parent cyanocobalamin is a true vitamin, and its biologically activated forms adenosylcobalamin and methylcobalamin, with their covalent cobalt-carbon bonds, are organometallic compounds. For these reasons, we begin by discussing the vitamin B12 coenzymes. The structure in fig. 4-1 is that of adenosylcobalamin, the first B12 coenzyme to be discovered. The molecule consists of the tetradentate corrin ring, cobalt in its 3+ oxidation state held within the corrin ring, the lower axial dimethylbenzimidazole α-ribotide ligand linked by a phosphodiester group to the corrin, and the 5'-deoxyadenosyl moiety covalently bonded to cobalt. The corrin ring is structurally and biosynthetically related to heme, but it differs in a number of respects, including that it is more highly reduced and incorporates extensive stereochemistry.