Priority rules

The priority rules we defined in Chapter 5 for describing the configuration of geometric isomers also apply to R,S configurational nomenclature for chiral compounds. 

Atoms Rank the four atoms bonded to a chiral carbon atom in order of decreasing atomic number the lower the atomic number, the lower the priority. Isotopes are ranked in order of decreasing mass. For example, (deuterium) H. 

Groups of atoms If a chiral atom is attached to two or more identical atoms, move down the chain until a difference is encountered. Then apply rule 1. Using this rule, we find that the priority of alkyl groups is 

The priority order for common functional groups containing oxygen is 

We can use the R,S system to describe the configuration of the enantiomers of alanine, which has a chiral center bonded to a hydrogen atom, a methyl group, a carboxyhc acid group, and an amino group (NHj). A perspective drawing of the enantiomer of alanine isolated from proteins is shown below. It has an S configuration. 

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The priority rules in Table 5 1 were developed by R S Cahn and Sir Christopher In gold (England) and Vladimir Prelog (Switzerland) in the context of a different aspect of organic stereochemistry they will appear again in Chapter 7... 

Cahn-Ingold-Prelog Priority Rules (Table 5 1, p 175)... 

The numbering of the complete fused structure does not depend on the original numbering systems of its components. Assignment of numbering requires (i) correct orientation of the structure and (ii) application of a rather intricate set of priority rules. For details, the lUPAC Rules should be consulted, but in outline the procedure is as follows. 

To avoid potential uncertainties in the application of the Cahn-Ingold-Prelog priority rules, by convention the enolate oxygen is assigned the higher priority. 

If no conflict free shortest path can be found, the conflict resolution tries to solve the conflict by waiting, speed reduction or evasion of the currently considered AGV. The applied priority rule is a First-Come-First-Serve heuristic. By using a FCFS-priority rule, paths that were once scheduled stay conflict free in the future [6, 7]. If the detected conflict can be solved, the resulting path is again analyzed for conflicts because new conflicts can emerge from the resolution of an earlier conflict. 

Serine hydroxymethyl transferase catalyzes the decarboxylation reaction of a-amino-a-methylmalonic acid to give (J )-a-aminopropionic acid with retention of configuration [1]. The reaction of methylmalonyl-CoA catalyzed by malonyl-coenzyme A decarboxylase also proceeds with perfect retention of configuration, but the notation of the absolute configuration is reversed in accordance with the CIP-priority rule [2]. Of course, water is a good proton source and, if it comes in contact with these reactants, the product of decarboxylation should be a one-to-one mixture of the two enantiomers. Thus, the stereoselectivity of the reaction indicates that the reaction environment is highly hydro-phobic, so that no free water molecule attacks the intermediate. Even if some water molecules are present in the active site of the enzyme, they are entirely under the control of the enzyme. If this type of reaction can be realized using synthetic substrates, a new method will be developed for the preparation of optically active carboxylic acids that have a chiral center at the a-position. 

Note use any sequence. For this purpose we do not need to obey any priority rules... 

The remaining part of the procedure is to assign the priorities. The lUPAC priority rules form a rather long... 

Note also that the configuration (R) or (S) is defined by the priority rules, and configuration (R) could easily become (S) merely by altering one substituent. For instance, all the amino acids found in proteins can be represented by the formula... 

If compounds contain different isotopes, e.g., hydrogen and deuterium, the priority rules are applied first to the atomic numbers. If this does not give an unambiguous assignment, the higher-mass-number isotope is given priority. 

Notice that in the previous examples, the atom of the higher atomic weight is given the higher priority (Br = 79.1 versus Cl = 15.5, and I = 126.0 versus N = 14.0). These assignments are based on the priority rules of Cahn-Ingold-Prelog nomenclature. 

ADTN. For both compounds, the R enantiomers are active. Sequence priority rules assign both as having the R configuration, but in fact the stereochemistries of the two compounds are reversed at their chiral carbon atoms. Thus, McDermed suggested... 

The substituents are listed according to the priority rules of Cahn-Ingold-Prelog in descending order. Preparative procedures are marked by a page number in bold-face type. Educts (starting material) as opposed to products are marked by a page number in italic-face type. 

These priority rules are also used to assign Eand Zto alkenes. (see p. 4B7) and are sometimes called the Cahn-lngold-Preiog (CIP) rules, after their devisors. 

Because of the nature of the priority rules [32], substrates sometimes differ in formal chirality, but nevertheless have essentially the same handedness [51,52]. Such reactions are homofacial rather than homochiral. The problem is of nomenclature interpretation for the enzymologist, not of stereospecific recognition by the enzyme. 

Step [1] Assign priorities to the two substituents on each end of the C=C by using the priority rules for R,S nomenclature (Section 5.6). 

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