Stereochemical numbering system

Stereochemical numbering. In some prochiral molecules, such as glycerol, the two ends of the main carbon chain form identical groups. Since the two ends are distinguishable to an enzyme, it is important to decide which should be labeled C-1 and which C-3. Hirschmann proposed a stereochemical numbering system in which the carbons are numbered beginning with the end of the chain that occupies the pro-S position. 

Fig. 4. Application of the stereochemical numbering system to acylglycerols. (From Gurr and James, 1980, reproduced by permission of Associated Book Publishers Ltd.)...

The. stereochemistry of vitamin A and related compounds is complex, and a complete. stereochemical analysis is beyond the. scope of this chapter. A brief. summary of some stereochemical features is prc.scnied here as the basis for the characterization of the biochemical actions exerted by this vitamin. Tlte study of the structural relationships among vita-ntin A and its stereoisomers has been complicated by the common use of several numbering. system.s. as. shown below. The first numbering sy.stem (A) is the one currently recommended by the International Union of Pure and Applied Chemistry (lUPAC). The second sy.stem (B) places emphasis on the conjugated tt. system, while the third (C) is used by the USP Dictionary of USAN and International Drug Names. 

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. 

FIGURE 3.4 Stereochemical projection of a generic diacylglycerol illustrating the stereochemical numbering (sn) system and the chiral center at the sn-2 carbon. Each molecule, although identical in formula, is a stereoisomer (specifically an enantiomer, a nonsuperim-posable mirror image). Rj and Rj represent substituent aUcyl chains. 

It is important to appreciate that, in stereochemical terms, the positions occupied by the acid chains are not identical. Under the stereospecific numbering system the positions are designated sn-1, sn-2 and sn-3, as shown.They are readily distinguished by enzymes and this may lead to preferential reactivity at one or more of the positions. Phosphorylation, for example, always takes place at carbon atom sn-3 rather than at carbon atom sn-1. Although triacylglycerols are predominant, mono- and di-acylglycerols do occur naturally, but in much smaller amounts. 

Stereochemical numbering (sn) system will be utilized when referring to the configuration of chemical substituents. In this system, the glycerol backbone can be envisioned in a vertical orientation with the uppermost carbon (C-1) as sn-l, the middle carbon (C-2) as sn-2, and the lowest carbon (C-3) as sn-3 (Figure 1). In this nomenclature, the phosphate of glycerophospholipids is assigned to the sn-3 position. 

A number of optically active, heteroatom-substituted carboxylic acid derivatives are excellent substrates for diastereoselective alkylation reactions. The ready availability of such chiral a-, (3-, and y-heteroatom-substituted carboxylic acid derivatives from the chiral pool and, more recently, through the implementation of catalytic, enantioselective methods (such as enantio-selective reduction of / keto esters Chapter 2, Section 2.7) makes this class of alkylations useful for the construction of stereochemically complex systems, particularly those containing quaternary stereogenic centers [54]. Key pioneering experiments in this area were disclosed independently by See-bach [55] and Prater [56]. 

The replacement of carbon by other elements produces changes in several structural parameters and consequently affects the conformational characteristics of the molecule. In this section, we will first describe some stereochemical features of heterocyclic analogs of cycloalkanes. For the purpose of elaborating conformational principles, the discussion will focus on six-membered rings, so that the properties may be considered in the context of a ring system possessing a limited number of low-energy conformations. 

The stereochemical designations employed for organometallic complexes follow an extension of the CIP system2. In all cases, the chiral metal atom has a higher atomic number and thus receives priority. The main feature of this extension of the CIP system concerns treatment of polyhapto ligands such as cyclopentadienyl ... 

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