Camphor enantiomers

Figure 16. Carbonyl C PECD from enantiomers of camphor. The experimentally derived data (Ref. [56]) for the (iS)-enantiomer have been negated prior to plotting on expectation that they will then fall on the same trend line as the (/ )-enantiomer data. The CMS-Xa and B-spline calculations (Ref. [57]) for the (R)-camphor enantiomer are included for comparison. The inset shows the (R)-camphor structure.

Schlichting I, Jung C, Schulze H. Crystal structure of cytochrome P-450cam complexed with the (lS)-camphor enantiomer. FEBS Lett 1997 415 253-257. 

Bioassays of 74 and 74 in Australia showed them to be equally active as the pheromone. However, B. bibax produces only (3R,4S)-74 as revealed by GC analysis.24 Thus, spined citrus bugs in Australia do not discriminate between the enantiomers of their aggregation pheromone. This is similar to the fact that even a perfumer cannot discriminate between camphor enantiomers. 

Multicopy molecular dynamics simulations suggest how to reconcile crystallographic and product formation data for camphor enantiomers bound to cytochrome P-450cam. J. Inorg. Biochem. 81, 121-131. 

Systematic studies of relaxation rates, preferably at more than one magnetic field strength, provide, in addition to a simple differentiation of enantiomers, information about complex formation and its dynamics. For example, longitudinal relaxation rates were determined in the study of the tryptophan-a-CyD complex in D2O [70]. A difference in the anisotropic tumbling of (+)camphor enantiomers inside the capsule formed by two a-CyD molecules in D2O was elucidated from the analysis of longitudinal and transverse relaxation rates at two magnetic field strengths [10]. 

Fig. 9.11. EnantiodifFerentiation of HIO(C)/ H3(H) NOE correlations in complexes of a racemic mixture of camphor enantiomers with a-CyD. Much stronger interaction in...

Dodziuk H, Ejchart A, Lukin O, Vysotsky MO. H and C NMR and molecular dynamics study of chiral recognition of camphor enantiomers by a-cyclodextrin. J. Org. Chem. 1999 64 1502 1507. 

In bridged bicyclic ring systems, two rings share more than two atoms. In these cases, there may be fewer than 2" isomers because of the structure of the system. For example, there are only two isomers of camphor (a pair of enantiomers), although it has two chiral carbons. In both isomers, the methyl and hydrogen are cis. The trans pair of enantiomers is impossible in this case, since the bridge must be cis. The... 

There are two chiral centres In (47) so a mixture of diastereoisomers is produced in 75 and 15% yields. Fortunately the major isomer is the analgesic. In fact only one enantiomer of this diastereo isomer is analgesic and so (48) is resolved with camphor sulphonic acid before esterification. The other enantiomer is a useful cough suppressant. 

Figure 17. Camphor PECD from the HOMO (carbonyl oxygen lone-pair) ionization. Experimental data are (S)-camphor, (R)-camphor (both from Ref. [36]) (R)- and (S)-enantiomer data from Ref [64] O data from Ref [65]. Also shown as curves are CMS-Xa calculations (Ref. [36]) and B-spline calculations (Ref [57]).

Figure 19. Camphor outer-valence orbitals generated from a HF/cc-pVDZ calculation. The (R)- enantiomer is oriented with its carbonyl group toward bottom left in the figure. The two stereogenic centers (asymmetric carbons) in the molecule are indicated by arrows.

Jones KH, RT Smith, PW Trudgill (1993) Diketocamphane enantiomer-specific Bayer-Villiger monooxygenases from camphor-grown Pseudomonas putida ATCC 17453. J Gen Microbiol 139 797-805. 

Figure 8.43 Separation of enantiomers using complexation chromatography. A, Separation of alkyloxiranes on a 42 m x 0.2S mm I.O. open tubular column coated with 0.06 M Mn(II) bis-3-(pentafluoro-propionyl)-IR-camphorate in OV-ioi at 40 C. B, Separation of D,L-amino acids by reversed-phase liquid chromatography using a mobile phase containing 0.005 M L-histidine methyl ester and 0.0025 M copper sulfate in an ammonium acetate buffer at pH 5.5. A stepwise gradient using increasing amounts of acetonitrile was used for this separation.

Gotti et al. [42] reported an analytical study of penicillamine in pharmaceuticals by capillary zone electrophoresis. Dispersions of the drug (0.4 mg/mL for the determination of (/q-penicillaminc in water containing 0.03% of the internal standard, S -met hy I - r-cystei ne, were injected at 5 kPa for 10 seconds into the capillary (48.5 cm x 50 pm i.d., 40 cm to detector). Electrophoresis was carried out at 15 °C and 30 kV, with a pH 2.5 buffer of 50 mM potassium phosphate and detection at 200 rnn. Calibration graphs were linear for 0.2-0.6 pg/mL (detection limit = 90 pM). For a more sensitive determination of penicillamine, or for the separation of its enantiomers, a derivative was prepared. Solutions (0.5 mL, final concentration 20 pg/mL) in 10 mM phosphate buffer (pH 8) were mixed with 1 mL of methanolic 0.015% 1,1 -[ethylidenebis-(sulfonyl)]bis-benzene and, after 2 min, with 0.5 mL of pH 2.5 phosphate buffer. An internal standard (0.03% tryptophan, 0.15 mL) was added and aliquots were injected. With the same pH 2.5 buffer and detection at 220 nm, calibration graphs were linear for 9.3-37.2 pg/mL, with a detection limit of 2.5 pM. For the determination of small amounts of (L)-penicillamine impurity, the final analyte concentration was 75 pg/mL, the pH 2.5 buffer contained 5 mM beta-cyclodextrin and 30 mM (+)-camphor-10-sulfonic acid, with a voltage of 20 kV, and detection at 220 nm. Calibration graphs were linear for 0.5-2% of the toxic (L)-enantiomer, with a detection limit of 0.3%. 

Because both enantiomers, (+) and (-)-camphoric add, are available by oxidation either from natural (+)-D-camphor or from natural (-)-L-borneol, both enantiomers of camphanoyl chloride can be prepared conveniently.3 5 The corresponding enantiomers of camphanic acid were described for the first time by Wreden6and Aschan.7 The three-step procedure, described above is an adaptation of procedures described by Aschan,8 Zelinsky et al.,9 Meyer et al.,10 and Gerlach.3... 

Certain pairs of enantiomers, such as 25°C solutions of camphor in aqueous ethanol (Fig. 26a), 2,2,5,5-tetramethyl-l-pyrrolidinoxy-3-carboxylic acid in chloroform (Fig. 26b), or carvoxime in hexane (Fig. 26c), cocrystallize throughout the entire range of mole fractions. The crystals that are in equilibrium with the saturated liquid solution are solid solutions (mixed crystals), since they constitute a single phase. The racemic solid solution is termed a pseudoracemate [141]. 

A homochiral tripod ligand thus can be obtained from a C2 symmetric precursor without additional separation of enantiomers or diastereomers. As an example for this concept we chose bis(camphor-pyrazol-l-yl)methane as starting material to afford an enantiopure but C2 symmetric bidentate ligand which is obtained in three steps from (-l-)-camphor (Scheme 17). 

Another aspect of the chemical properties of mixmres of enantiomers has been reported by Wynberg and Feringa in 1976. These authors have smdied some dia-stereoselective reactions on chiral molecules (such as the LiAlH4 reduction of camphor) in the absence of chiral auxiliaries. They found that the product distribution was significantly different if the substrate was enantiopure or racemic. Similarly, it is known that reduction of enantiopure or racemic camphor by K/liquid NH3 gives rise to different isobomeol/bomeol ratios, a detailed mechanistic analysis has been done by Rautenstrauch. °... 

Chrysanthemum parthenium oil [100%(15,45)(—)] and the two chemotypes of Artemisia judaica oils contained (15,45)(—)-camphor as the dominant enantiomer. The (15,45)(—)-enantiomer, with high enantiomeric purity, was detected in two types of 5. ojjjcinalis and in Coriandrum sativum (15,45) (-)-Camphor has been reported in the oils of 5. grandiflora, 5. fruticosa, Matriearia parthenium and in other... 

Each bridgehead C is a chiral centre. Camphor, with two different chiral C s must be expected to have 2 or four stereoisomers existing as two racemic forms but only one is known. The bridge must be cis as shown. The structural impossibility of a trans bridge eliminates a pair of enantiomers. 

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