Diastereomeric camphanates

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. 

As this synthesis started from an achiral starting material, compound 199 must be resolved to secure enantiomerically pure intermediates for the synthesis of taxol. Treatment of (+ )-diol 199 with excess ( lA)-( )-camphanic chloride in methylene chloride in the presence of Et3N forms two diastereomeric monoesters for chromatographic separation. Enantiomerically pure diol 199 can be regenerated from the ester in 90% yield with a specific rotation of +187 (c = 0.5, CHC13). 

Oxabicyclo[6.3.2]trideca-l(ll),8,12-trienes (3,6-hexanooxepine) [15, R = CH2OH]83 was resolved via the diastereomeric esters with (lS ,4iR)-camphanic acid. X-ray analysis of one of the esters was used for configurational assignment (see p 447). 

The diastereomeric esters that resulted from rat-8a with (—)-camphanic acid were separated, and an X-ray analysis established the configuration of one of the esters. This compound was then converted via 8b into D3-trishomocubane (—)-9159. 

Racemic thiochroman-4-ol has been resolved by conversion to the diastereomeric camphanyl esters by reaction with (—)-(lV)-camphanic chloride and fractional crystallization. A p Tr value of —12.3 has been obtained for the ionization of this alcohol and rate constants for the racemization of chiral thiochroman-4-ol have been obtained in water and in a water-trifluoroethanol (1 1) mixture <2004JA9982>. 

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). ... 

Monoesters of diastereomeric 1,2-diols can be prepared from oxiranes with camphanic acid. The acetolysis of epoxycyclopentanes and further transformations of the unexpected product of acetolysis (Eq. 314) have been followed in acidic and basic media. 

In the case of the halogenated alcohols 14 and 15, their diastereomeric CSDP esters were obtained as fine crystals, which were unsuitable for X-ray crystallography, so the enantiopure alcohol recovered (—)-14 was converted to camphanate ester, the absolute configuration of which was determined by X-ray crystallography as R (entry 4). Alcohol ( )-15 was treated in the same way, but its caphanate ester was not suitable for X-ray analysis (entry 5). The absolute configuration of ( )-15 was determined as R by comparison of its CD spectrum with that of (P)-(-)-14. 

Introduction. Enantiomerically pure alcohols can frequently be obtained by physical separation of the diastereomeric esters prepared from the racemic alcohols and chiral acids. Chiral acids that have been successfully employed for this purpose and are available in either enantiomeric form include < -camphanic acid and the monomethyl ester of diacetyltartaric acid. No reagent can be considered generally applicable to all alcohols, since the ease of separation of the diastereomeric esters frequently depends on their crystallinity and/or chromatographic properties. A successful resolution is frequently the result of multiple trials and errors with a variety of acids. 

Cryptophanes 1 and 4, described in Sect. 21.2.1, are the two first optically active water-soluble compounds synthesized from cryptophanol-A 2. The single phenol function in 2 can easily react with a small chiral auxiliary (e.g., camphanic acid chloride) to provide the two diastereomeric species 41 and 42 (Fig. 21.10) [36]. The two diastereomers can be isolated by crystallization in toluene, and the two enantiomers of 2 can then be recovered after hydrolysis under basic solutirai and then re-used for subsequent reactions. The interest of this strategy is twofold (i) it provides fair quantities of optically active cryptophanol-A 2 with high enantiomeric excess (ee = 98-100%) (ii) it allows the preparation of new optically active cryptophanes without any loss of enantiomeric excess. Thus, starting from... 

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