Homochirality

Homochirality is the choice in Nature for one handedness or another. Macroscopic homochirality can be observed in the winding of some species of snail shell 

For the dichroic photolysis mechanism to be successful, amino acids must be synthesised and destroyed in an intense circularly polarised radiation field. Daylight shows little or no excess but recent observations at 2.2 /rm of the Orion reflection nebula OMC-1 shows polarisations in excess of 17 per cent, although 

The discovery of homochirality on a planet such as Mars could be an excellent biomarker and strengthen the argument for life on Mars. With an EE in the solar nebula there should be an EE on the surface of Mars of order 9 per cent but remains of ancient life on Mars would show a greater excess. The interchange of enantiomers occurs naturally in a process called racemisation and for the most labile amino acid, aspartic acid, the half-life for the racemisation is 800 years at 300 K in 800 years, half of the non-biotic aspartic acid would racemise and the EE would go to zero. In dry conditions, however, the half-life is much longer, perhaps as large as 5 x 104 years at 300 K. Extrapolation of the racemisation rate to 215 K, the equatorial temperature of Mars, extends the half-life further to 3 x 1012 years and to 1027 years at 150 K, Martian polar temperatures. Hence, discovery of a considerable EE in the Martian soil would be a strong indicator of ancient Martian life. 

---

A particular point of interest included in these hehcal complexes concerns the chirality. The heUcates obtained from the achiral strands are a racemic mixture of left- and right-handed double heUces (Fig. 34) (202). This special mode of recognition where homochiral supramolecular entities, as a consequence of homochiral self-recognition, result from racemic components is known as optical self-resolution (203). It appears in certain cases from racemic solutions or melts (spontaneous resolution) and is often quoted as one of the possible sources of optical resolution in the biological world. On the other hand, the more commonly found process of heterochiral self-recognition gives rise to a racemic supramolecular assembly of enantio pairs (204). 

One of the homochiral starting materials (45) for the acetylcholinesterase (ACE) inhibitor captopril [62571 -86-2] (47) is produced by a Hpase enzyme-catalyzed resolution of racemic 3-methyl-4-acetylthiobutyric acid (44) and L-proline (46) (65). 

Fig. 7. Preparation of Alpine-borane (93) and use in the synthesis of homochiral butyrolactones and arylhydroxytetronic acids. Rg and denote small and...

Over 50% of clinically available dmgs have chiral centers and only about 10% of synthetic chiral dmgs are marketed in homochiral (enantiomerically pure) form (33). In contrast, dmgs that are naturally occurring substances, obtained from or related to naturally occurring molecules, are frequendy homochiral. 

There is increasing pressure to develop homochiral dmgs (34). Growing demands are faced by the pharmaceutical industry in dmg development to consider chiral issues in the eady preclinical phases of dmg design and synthesis. 

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

Derivatization with Optically Active Reagents and Separation on Achiral Columns. This method has been reviewed (65) a great number of homochiral derivatizing agents (HD A) are described together with many appHcations. An important group is the chloroformate HD As. The reaction of chloroformate HD As with racemic, amino-containing compounds yields carbamates, which are easily separated on conventional hplc columns, eg (66),... 

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

The reaction products are the same for both direct irradiation and acetophenone sensitization. When the reactant B is used in homochiral form, the product D is nearly racemic (6% e.e.). Relate the formation of the cyclobutanones to the more normal products of type E and E Why does the 5-aryl substituent favor formation of the cyclobutanones Give a complete mechanism for formation of D which is consistent with the stereochemical result. 

Homochiral thiiranium and aziridinium ion intermediates formed by Lewis acid-induced rearrangement of l-hetero-2, 3-epoxides 97SL11. 

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

Different optical enantiomers of amino acids also have different properties. L-asparagine, for example, tastes bitter while D-asparagine tastes sweet (see Figure 8.3). L-Phenylalanine is a constituent of the artificial sweetener aspartame (Figure 8.3). When one uses D-phenylalanine the same compound tastes bitter. These examples clearly demonstrate the importance of the use of homochiral compounds. 

This review is not comprehensive but emphasizes the more recent literature through 1985 into early 1986. References to earlier work are included in an affort to make the subject understandable to those unfamiliar with past research and also to cover topics not touched upon in recent publications. The term optically active is used here in the sense that the chiral molecule under discussion is nonracemic but not necessarily enantiomerically pure. The terms homochiral and optically pure are used synonymously with enantiomerically pure. 

Racemic mixtures of sulfoxides have often been separated completely or partially into the enantiomers. Various resolution techniques have been used, but the most important method has been via diastereomeric salt formation. Recently, resolution via complex formation between sulfoxides and homochiral compounds has been demonstrated and will likely prove of increasing importance as a method of separating enantiomers. Preparative liquid chromatography on chiral columns may also prove increasingly important it already is very useful on an analytical scale for the determination of enantiomeric purity. 

Preparation of the appropriate optically active sulfmate ester is initially required for reaction with a Grignard or other organometallic reagent. If the method is to produce homochiral sulfoxides, the precursor sulfmate ester must be optically pure. An exception to this statement occurs if the reaction yields a partially racemic sulfoxide which can be recrystallized to complete optical purity. 

---