Optical activity and configuration

Amino acids, except for glycine, have at least one chiral center and, hence, are optically active. All amino acids found in proteins have the same configuration on the a-C-atom they are considered L-amino acids or (S)-amino acids in the Cahn-Ingold-Prelog system (with L-cysteine an exception it is in the (R)-series). D-amino acids (or (R)-amino acids) also occur in nature, for example, in a number of peptides of microbial origin  

Isoleucine, threonine and 4-hydroxyproline have two asymmetric C-atoms, thus each has four isomers  

L-Isoleucine (2S 3S)-Isoleucine (Common in proteins) D-Isoleucine (2R 3R)- Isoleucine L-allo- D-allo Isoleucine Isoleucine (2S 3R)- 12R 3S)-Isoleucine Isoleucine (1.8)  

The specific rotation of amino acids in aqueous solution is strongly influenced by pH. It passes through a minimum in the neutral pH range and rises after addition of acids or bases (Table 1.3). There are various possible methods of separating the racemates which generally occur in amino acid synthesis (cf. 1.2.5). Selective crystallization of an over-saturated solution of racemate after seeding with an enantiomer is used, as is the fractioned crystallization of diastereomeric salts or other derivatives, 

The detection of D-amino acids is carried out by enantioselective HPLC or GC of chiral amino acid derivatives. In a frequently applied method, the derivatives are produced in a precolumn by reaction with o-phthalaldehyde and a chiral thiol (cf. 1.2.4.2.4). Alternatively, the amino acids can be transformed into trifluoroacetylamino acid-2-(R,S)-butylesters. Their GC separation is shown in Fig. 1.3. 

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Triptycene derivatives are more interesting in clarifying the relation between their configurations and optical activity. The results published by Tanaka28) were not in... 

Recendy, Darzens reaction was investigated for its synthetic applicability to the condensation of substituted cyclohexanes and optically active a-chloroesters (derived from (-)-phenylmenthol). In this report, it was found that reaction between chloroester 44 and cyclohexanone 43 provided an 84% yield with 78 22 selectivity for the axial glycidic ester 45 over equatorial glycidic ester 46 both having the R configuration at the epoxide stereocenter. 

Raney cobalt is generally less effective than Raney nickel, but may be of use when the rupture of other bonds must be avoided. The important use of Raney nickel desulfurization for the structure determination of thiophenes and for the determination of the absolute configuration of optically active thiophene and benzene derivatives has been stressed earlier. 

Utilization of the Pfeiffer effect and outer-sphere complexation for the prediction of absolute configurations of optically active metal complexes. S. Kirschner and I. Bakkar, Coord. Chem. Rev., 1982,43, 325-335 (27). 

CD and ORD measurements are a useful tool in studying configuration and conformation. The configuration of optically active 4,4 -dicarboxy-2,2, 5,5 -tetramethyl-3,3 -biselenienyl (1, X = Se) relative to its thiophene analog (1, X = S), was determined by reducing both to the corresponding 4,4 -dihydroxymethyl derivatives (2), which could be related to each other by the quasi-racemate method and by circular dichroism studies.15 Compounds 1 have also been related to 3,3, 6,6 -tetramethyl-2,2 -diphenic acid (3), and it was found that the levorotatory form of 1 (X = Se, S) and the dextrorotatory form of 3 have the -configuration.16... 

Glowiak, T. and Sawka-Dobrowolska, W., Absolute configuration of optically active aminophosphonic acids, Tetrahedron Lett., 3965, 1977. 

Chiral sulfinates are important intermediates that are widely applied in the synthesis of other classes of chiral organosulfur compounds and in their configurational correlations. Optically active sulfinates were first prepared in 1925 by Phillips (100) in two ways. The first consisted in the transesterification of racemic alkyl p-toluenesulfin-ates with chiral alcohols such as (-)-menthol and (-)-2-octanol yielding a mixture of two optically active sulfinates as shown in eq. [26]. The... 

When benzylideneaniline is reacted with ylide 162b, optically active N-phenyl-2-phenylaziridine 261 of unknown absolute configuration and optical purity is produced (294). 

It is of some interest that optically active spiroketone 262 is formed when tra/i5-benzalacetophenone is treated with ylide 162g (295). The absolute configuration and optical purity of this ketone are unknown. 

Another compound of considerable radiopharmaceutical relevance and based on dithiolato donors is the Tc complex of dimercaptosuccinic acid (H2dmsa, (95)). The ligand (95) has both a meso and optically active forms, leading to complexes of different stereochemical configuration, which have very different in vivo behavior. Whereas the complex from racemic (95) leads to a product that is renally excreted without accumulation in any other organ, the complex prepared from... 

Methyl sorbate and analogous monomers were polymerized in the presence of (/ )-2-methylbutyllithium or of complexes between butyllithium and optically active Lewis bases (329, 330) (see formulas 32 and 33) the polymers show weak optical activity. The prevailing configuration of the — CH(CH3)— group was determined by the sign of rotation of the methylsuccinic acid obtained from the polymer after ozonization. The low optical purity ( = 6%) found is related to the presence of a remarkable stereochemical disorder (115, 116) and to the fact that the chiral agent is active, at least in the case of methylbutyllithium, only in the initiation reaction. 

Similarily, the 4,14-dicarboxylic acid 56 with C2-symmetry could also be resolved via its 1-phenylethylamine salts and its configuration unambiguously correlated with the monocarboxylic acid 55 through the monobromo derivative 5878). Accordingly 55 and 56 with the same sign of optical rotation have the same chirality. Many racemic and optically active homo- and heterodisubstituted 4,12- and 4,14-disubstituted [2.2]metacyclophanes have been prepared and chemically correlated 78,79) mainly to study their chiroptical properties78). Whereas 4,12-homodisubstituted compounds have a center of inversion ( -symmetry) and are therefore achiral meso-forms , the corresponding 4,14-isomers are chiral with C2-symmetry. All heterodisubstituted products are chiral (Q-symmetry see also Section 2.9.4 for the discussion of their chiroptical properties and their use as models for the application of the theory of chirality functions). 

Sodium-naphthalene reduction of organotrineopentoxyphosphonium salts led to the instantaneous loss of phosphonium ion phosphonates and phosphites were obtained748 (reaction 224). Alkali metal amalgams are efficient reagents for the reductive cleavage of both achiral and optically active phosphonium salts configuration is retained750 (Table 23). 

Table 7. Relationship between absolute configuration of some a-olefins and optical activity sign of their polymers...

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