Carbonic acid optically active

What is interesting, however, is some of the chemistry that is not present. For example, the petrochemical industry does not have a basic feedstock in the five-carbon area and thus we see few products derived from or based on five-carbon chemistry. Optical active compounds are also missing from the petrochemical-derived product list. For example, lactic acid is now made exclusively from glucose, with the reason being that the fermentation route provides stereochemical purity that is difficult to achieve from petrochemical building blocks. 

Ti measurements performed on cyclic dipeptides in dimethyl-sulfoxide-dg revealed a correlation between the molecular weight of the dipeptide and the value of the a-carbon of optically active amino acid residues. These are shown in Figure 26 (Deslauriers et al, 1975b). According to the Debye-Stokes-Einstein equation, the correlation plotted in dotted lines is to be expected. The discrepancy between observed and calculated values is worse for the lower-molecular-weight dipeptides. For dipeptides... 

Figure 26. Observed (o) correlation between molecular weight of diketopiperazines and Ti values of a carbons of optically active amino acids in various diketopiperazines. values are calculated ( ) assuming isotropic overall reorientation of a rigid sphere (Deslauriers et aU 1975b).

A molecule is chiral if it cannot be superimposed on its mirror image (or if it does not possess an alternating axis of symmetry) and would exhibit optical activity, i.e. lead to the rotation of the plane of polarization of polarized light. Lactic acid, which has the structure (2 mirror images) shown exhibits molecular chirality. In this the central carbon atom is said to be chiral but strictly it is the environment which is chiral. 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

The reaction can be used ia the large-scale production of the optically active amino acid detivatives. The chiraUty of the a-carbon is substantially retained and resolution of the product is avoided. 

The asterisk signifies an asymmetric carbon. AH of the amino acids, except glycine, have two optically active isomers designated D- or L-. Isoleucine and threonine also have centers of asymmetry at their P-carbon atoms (1,10). Protein amino acids are of the L-a-form (1,10) as illustrated in Table 1. 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaHy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphoms [7723-14-0] produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-Hthiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has Httie commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

Optically Active Acids and Esters. Enantioselective hydrolysis of esters of simple alcohols is a common method for the production of pure enantiomers of esters or the corresponding acids. Several representative examples are summarized ia Table 4. Lipases, esterases, and proteases accept a wide variety of esters and convert them to the corresponding acids, often ia a highly enantioselective manner. For example, the hydrolysis of (R)-methyl hydratropate [34083-55-1] (40) catalyzed by Hpase P from Amano results ia the corresponding acid ia 50% yield and 95% ee (56). Various substituents on the a-carbon (41—44) are readily tolerated by both Upases and proteases without reduction ia selectivity (57—60). The enantioselectivity of many Upases is not significantly affected by changes ia the alcohol component. As a result, activated esters may be used as a means of enhancing the reaction rate. 

Two pieces of chemical evidence support the three-membered ring formulation. The bifunctional oxazirane prepared from glyoxal, tert-butylamine, and peracetic acid (6) can be obtained in two crystalline isomeric forms. According to the three-membered ring formula there should be two asymmetric carbon atoms which should allow the existence of meso and racemic forms. A partial optical resolution was carried out with 2-7i-propyl-3-methyl-3-isobutyloxazirane. Brucine was oxidized to the N-oxide with excess of the oxazirane. It was found that the unused oxazirane was optically active. 

Molecules that contain two or more asymmetric centers exist in more than two stereoisomeric forms. Some are pairs of optically active isomers others may be symmetric and therefore optically inactive. An example is tartaric acid with two asymmetric central carbon atoms. It has three isomers, two of which are optically active and one inactive. 

In all the amino acids shown in Table 23.3 except glycine, the a-carbon is chiral. This means that these compounds are optically active. With alanine, for example, there should be two optical isomers ... 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

Tin/lithium exchange on the a-alkoxy stannanes and subsequent addition of carbon dioxide led to optically active (7-protected a-hydroxy acids 18 with retention of configuration and without any loss of stereochemical information11. 

The a-substitution of enantiomerically enriched (-)-sparteine complexes of lithioalkenyl carbamates with methyl chloroformate76 or carbon dioxide77, in a manner contrary to a former assumption 76, proceeds with inversion of the configuration 131 131, leading to optically active 3-alkenoic acid esters. 

An interesting aspect of the benzofuran cationic polymerization was uncovered by Natta, Farina, Peraldo and Bressan who reported in 196160,61 that an asymmetric synthesis of an optically active poly(benzofuran) could be achieved by using AlCl2Et coupled with (-)j3-phenylalanine, (+)camphorsulphonic acid or with (-)brucine. The optical activity was definitely due to the asymmetric carbon atoms in the polymer chain, indicating that at least some of the polymer s macromolecules possessed a di-isotactic structure, v/ z.62 ... 

Subsequently, a number of reactions at poly-L-valine coated carbon electrodes 237-243) gj.g reported to yield optically active products. Reductions, e.g. of citraconic acid or l,l-dibromo-2,2-diphenylcyclopropane as well as the oxidation of aryl-alkyl sulfides proceeded with chiral induction at such electrodes... 

Analogous results were obtained for enol ether bromination. The reaction of ring-substituted a-methoxy-styrenes (ref. 12) and ethoxyvinylethers (ref. 10), for example, leads to solvent-incorporated products in which only methanol attacks the carbon atom bearing the ether substituent. A nice application of these high regio-and chemoselectivities is found in the synthesis of optically active 2-alkylalkanoic acids (ref. 13). The key step of this asymmetric synthesis is the regioselective and chemoselective bromination of the enol ether 4 in which the chiral inductor is tartaric acid, one of the alcohol functions of which acts as an internal nucleophile (eqn. 2). 

Although the conversion of an aldehyde or a ketone to its enol tautomer is not generally a preparative procedure, the reactions do have their preparative aspects. If a full mole of base per mole of ketone is used, the enolate ion (10) is formed and can be isolated (see, e.g., 10-105). When enol ethers or esters are hydrolyzed, the enols initially formed immediately tautomerize to the aldehydes or ketones. In addition, the overall processes (forward plus reverse reactions) are often used for equilibration purposes. When an optically active compound in which the chirality is due to an asymmetric carbon a to a carbonyl group (as in 11) is treated with acid or base, racemization results. If there is another asymmetric center in the molecule. 

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