Horeau method

Turning now to chemical methods used for stereochemical studies of carotenoids the modified Horeau method (32) has been successfully used to confirm the configuration of (2/ )- 3, 3-caroten-2-ol [(33), R=H] (38) and to establish the configuration of aleuriaxanthin (36) (34). However, no conclusive results could be obtained for plectaniaxanthin [(35), R = R =H] (28). In principle the Horeau method is based on partial resolution of racemic and meso a-phenylbutyric anhydride by means of an optically active secondary alcohol, which readts preferentially with one diastereomer. The unreacted anhydride is quantitatively determined by an appropriate procedure (32, 68, 94). 

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If, according to a modified Horeau method (partial kinetic resolution of a racemate), an optically active carboxylic acid is treated with an excess of racemic amine or alcohol, the configuration of the carboxylic acid can be inferred from the optical rotation of the residual amine or alcohol [48]... 

This method, which in this empirical version has the same limitations as discussed above for the Horeau method, was recently employed in determining the absolute configuration of substituted 1 -phenylethanamines 254. 

The C-24 configurations of the isomeric 24-hydroxy-cholesterols have been firmly established5 by chemical correlation with the known 24R,25- and 24S,25-epoxyderivatives, and by the modified Horeau method.6 With the configurations known, differences in 13C n.m.r. spectra and in polarity were used to establish the configurations of the la,24-dihydroxy-derivatives of vitamin D3.5 Cerebrosterol , isolated from brain tissue, is 24S-hydroxycholesterol,6a but the natural 24,25-dihydroxy-vitamin D3 has the (24R) configuration. The C-24 isomeric 24,25-dihydroxy-cholesterols have also been separated and characterized.7... 

The previously described (24S)-24,25-epoxycholesteryl benzoate has been reduced with lithium aluminium hydride-aluminium chloride to give a chromato-graphically separable mixture of 25-hydroxycholesterol (55%) and (24S)-24-hydroxycholesterol (273),133 the configuration of which was determined by the modified Horeau method.135 It is interesting to note that cerebrosterol isolated from brain is (24S)-24-hydroxycholesterol whereas natural 24,25-dihydroxy-vitamin D3... 

A second new alkaloid, andrachcine (228) was isolated from Andrachne aspera. Its structure was determined using HRMS, IR, UV and lH NMR. Once again, application of the Horeau method led to assignment of the absolute configuration at the hydroxylated carbons as S,S [506],... 

The absolute configuration of the chiral axis in the naturally occurring skyrin molecule has remained an outstanding question for many years. Recently, the stereochemistry of (-h) Skyrin and of atrovirin-B has been established as ( S) by making use of an extension to the Horeau method 398). Thus, reaction of each of these compounds with ( )-2-phenylbutyric anhydride led to an excess of residual (-l-)-2-phe-nylbutyric acid, which was also the case when (S)-2,2 -dihydroxy-l,r-binaphthyl was used as the substrate and esterified under the same conditions. 

Fig. 38. The ORD curves of the 2-phenylbutyric acids, isolated from compounds 74-77 according to the Horeau method.

The configurational assignments are based on the Horeau method and chiroptical techniques, applied to the dihydrodeoxohumulinic acids (see 8.4.3.1.3.). This procedure has been explained in detail when the absolute configuration of the isohumulones was determined (see 5.1.3.2.). It follows that (+) ds humulinic acid (121) has the (4R,5S)-configuration and (-) trans humulinic acid (122) has the (4S.5S) configuration (33). 

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