Antipodes

Jl exists in this form only in solution, though stable derivatives of the aldehyde structure are known. The optical antipode of D-glucose in which the positions of every H and OH are transposed is L-glucose. 

Astemi2ole (10) has further been modified into a series of 4-phenylcyclohexylamine compounds, resulting in the synthesis of cabastine, for example. Cabastine is a highly active compound and its geometric isomers are also active, demonstrating the stereoselectivity of histamine receptors toward chiral ligands. The > S, 4 R-levo antipode of cabastine was the most active, and therefore this isomer, levocabastine (13), has been chosen for further development. Because of high potency, levocabastine has been developed for topical appHcation such as eye drops and nasal spray. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Levopropoxyphene [2338-37-6] (42), the optical antipode of the dextrorotatory analgetic propoxyphene, is an antitussive without analgetic activity. The 2-naphthalenesulfonate salt has a less unpleasant taste than the hydrochloride salt, and is widely used. Clinical effectiveness has been demonstrated against pathological and artificially induced cough, but the potency is somewhat less than codeine. The compound is reported not to cause addiction. Levopropoxyphene can be prepared (62) by first resolving [ -dimethylamino-CX-methylpropiophenone with dibenzoyl-(+)-tartaric acid. The resolved... 

Confirmation of this constitution was provided by Spath and Becke, > who identified 5-methoxy-3 4-methylenedioxy-o-phthalic acid as an oxidation product of anhalonine. The synthetic df-anhalonine was resolved by crystallisation of the f-tartrate from methyl alcohol, into f-anhalonine, m.p. 85-6°, — 56-3° (CHCI3) and its optical antipode,... 

Phaeanthine, C3JH42O0N2. (Item 8 list, p. 350.) This alkaloid was isolated by Santos.It has m.p. 210°, [a]u°° — 278° (CHCI3), yields a hydriodide, m.p. 268°, picrate, m.p. 263°, aurichloride, m.p. 170-1°, and a platinichloride, m.p. 280° (dec.), and contains four methoxyl and two methylimino groups. By the Hofmann degradation process it yields an optically inactive methine base A, m.p. 173°, which is oxidised by potassium permanganate in acetone to 2-methoxy-5 4 -dicarboxydiphenyl ether (p. 348). A comparison of the properties of phseanthine and tetrandrine by Kondo and Keimatsu indicates that these two alkaloids are optical antipodes, so that phseanthine will be represented by either (XXXIX) or (XL) as given on p. 348, 1 and of these two formula (R = Me) one must represent oxyacanthine methyl ether and the other berbamine methyl ether (centres of asymmetry d- and 1-) tetrandrine (centres of asymmetry both d-) and phseanthine (centres of asymmetry both 1-). 

The pronounced influence of the phenyl group on optical activity led Fredga and Palm" to initiate an investigation on the optical activity of thiophene derivatives, in order to use this physical property for the elucidation of the aromatic character of thiophene. 2-(27) and 3-Thenylsuccinic acid (28), 2- (29) and 3-thienyl-succinic acid (30), 2- (31) and 3-thienylglycolic acid (32), 2-(33) and 3-a-methoxythienylacetie acid (34), -phenyl 2-thienyl-glycolic acid (35), -(2-thienyl)-y5-phenylpropionic acid (36), a-phenyl- -(2-thienyl) propionic acid (37), a,/ -di (2-thienyl)propionic acid (38) have been resolved into antipodes with the help of optically active bases. 

The biologically important anti-/8-phenylalanine, /8-2-thienylalanine (39), has been resolved into antipodes through enzymatic resolution with carboxypeptidase/ The pharmacologically important 3-piperidino-l,i-bis-2-thienyl-l-butene (40), which crystallizes as. a conglomerate, has been resolved by hand picking. ... 

Beckmann has examined the characters of the optically active men-thones. The oxidation of natural Z-menthol by chromic acid mixture yielded Z-menthone [a]n = - 28 5° which when treated with 90 per cent, sulphuric acid is converted into a d-menthone [ajn = 4- 28 1°, which, however, is not the optical antipode of the first it behaves as a mixture of d- and Z-menthone, but is more strongly dextro-rotatory than it would be if it were only a mixture of the two optical antipodes. 

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

This observation is important in the study of the chiral recognition mechanism in this system. This may be a practical matter when determining the trace amount of one enantiomer in the presence of its dominant antipode. The smaller peak is always desired to be eluted first for best quantitation. 

Each racemate was applied on a polymer (ca. 0.1. imol per gram dry polymer) imprinted with one antipode of the racemate. Tlie standard mobile phase, consisting of acetonitrile containing various amounts of acetic acid, was used in most cases. Cbz = Carbobenzyloxy, Boc = t-butyloxycarbonyl. 

Stereo differences within the individual substitutes are not taken into account when we talk about antipodes. 

The coefficient of xV in the three expressions indicates that there exist four different derivatives of cyclopropane of the form (disubstituted cyclopropane with two identical substituents). Two of the four derivatives are mirror images of each other, that is, they form a pair of optical antipodes. If the spatial arrangement is disregarded, only two distinct cyclopropanes with formula are... 

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. 

A similar reaction in the antipodal series has been used for the synthesis of optically active 3-hydroxy-2-methylenealkanoates41. 

Moglichkeit zur Trennung von Racematen, da oft nur ein optischer Antipode veran-dert wird... 

Chiral heterocyclic compounds containing vicinal oxygen and nitrogen atoms were achieved by an asymmetric Diels-Alder reaction [111] of chiral acylnitroso dienophiles 111. The latter were prepared in situ from alcohols 110, both antipodes of which are available from camphor, and trapped with dienes (Scheme 2.46). Both the yield (65-94 %i) and diastereoisomeric excess (91-96%) were high. 

A representative set of a- and -keto esters was also tested as substrates (total 11) for each purified fusion protein (Figure 8.13b,c) [9bj. The stereoselectivities of -keto ester reductions depended both on the identity of the enzyme and the substrate stmcture, and some reductases yielded both l- and o-alcohols with high stereoselectivities. While a-keto esters were generally reduced with lower enantioselec-tivities, it was possible to identify pairs of yeast reductases that delivered both alcohol antipodes in optically pure form. These results demonstrate the power of genomic fusion protein libraries to identify appropriate biocatalysts rapidly and expedite process development. 

A major contribution to the field in recent years was the identification of subclusters of BVMOs with overlapping substrate acceptance providing access to antipodal... 

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