Camphanate method 15 -Camphanic acid

Both routes actually use vanilly alcohol 34 (3-methoxy-4-hydroxybenzyl alcohol) as the starting material. Application of method (a) requires that 34 could be trimerized to C3-cyclotriguaiacylene, 5 (Table 1). However, as was said above, this reaction does not work, presumably because the phenolic group makes the molecule too reactive under the strong acidic conditions employed the allyl protected derivative 35 was thus used instead of 34 itself, and, on reaction with perchloric acid in methanol, gave the tris-allyl protected derivative 9 in 55% yield. Palladium catalysed cleavage of the allyl groups then led to the desired racemic triphenol 5. The latter could eventually be resolved by separation of its dia-stereoisomeric esters with co-camphanic acid [13]. 

Resolution of Alcohols. In addition to generally providing highly crystalline derivatives that are usually suitable for X-ray crystallographic studies, diastereomeric esters derived from camphanic acid have been widely used in organic synthesis for the resolution of racemic alcohols by fractional crystallization or chromatography. This is one of the methods of choice to resolve inositol derivatives. Selected examples are shown in (7)-<10). ... 

The encouraging result of the trans-epoxy acylates with the chiral spiro compounds was appUed to the optically active system (Scheme 15). Asymmetric reduction of the enone 31 by Corey s method [72] afforded the allyl alcohol (-)-34 (90% ee). Epoxidation of (-)-34 by the stereoselective Sharpless epoxidation [73] afforded the cts-epoxy alcohol, cfs-(-)-35, as the sole product. The Mitsunobu reaction [74] of czs-(-)-35 with benzoic acid gave the trans-epoxy benzoate, trans- -)-36, (90% ee) in 89% yield. Treatment of trans-(-)-36 with BF3-Et20 afforded the optically active spiro compound (+)-37 in 89% yield with retention of the optical purity (90% ee). This means that the rearrangement occurs stereospecifically. The optically pure epoxy camphanate (-)-38 could be obtained after one recrystallization of the crude (-)-38 (90% de), which was obtained by the Mitsimobu reaction of cfs-(-)-35 with D-camphanic acid. The optically pure spiro compoimd (+)-39 (100% de) was obtained from the optically pure (-)-38 in 89% yield. 

Separation and Assay. Procedures for the separation, purification, and assay of carotenoids and retinoids by h.p.l.c., g.c., and g.c.-m.s. are given in an extensive article." Another, general, review includes information on the h.p.l.c. separation of retinoids.A particularly useful method has been developed for resolution and analysis of some carotenoid optical isomers.For example, (3R,3 R)-, (3S,3 S)-, and (3/ ,3 5)-astaxanthin were converted into the diastereomeric (-)-camphanic acid diesters, which were separated by h.p.l.c. This procedure has been used to analyse the isomeric composition of a natural astaxanthin sample. An h.p.l.c. procedure for separation of a-, P-, and y-carotenes (173)—(175) and lycopene (176) has been described." Several papers describe methods for the h.p.l.c. separation and purification of various retinal and retinol isomers and derivatives.A procedure for the preparative t.l.c. of oxidation products of retinyl acetate has been described,and a competitive protein-binding radioassay for retinoic has been reported. 

A typical example of this internal reference method is shown in Figure 55.5, where alcohol (—)-6 has a bromine atom but no single crystals suitable for X-ray diffraction analysis were obtained. Therefore, alcohol ( )-6 was esterified with (15)-(—)-camphanic acid 5 (CXR), yielding ester 7 as single crystals. From the X-ray stereostructure of ester 7, the AC of (—)-6 was unambiguously determined to heR. 

If you need any more convincing, applying the same method to flutriafol 66 gave the camphanic esters as before but now no separation could be achieved even with HPLC. Esters 69 of a different acid 68 could be separated on the same column but using 1 1 CH2Cl2/EtOAc as eluent. You will not be surprised to know that fluconazole 70 is now a leading fungicide in this area. It is not chiral. 

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