Inclusion cyanohydrin

ImHNL is a nonglycosylated homodimer (84 kDa) which catalyzes the reversible cleavage of aliphatic (R)-cyanohydrins [34]. This HNL does not require complex protein modification after protein biosynthesis. Thus, expression in prokaryotic Escherichia coli) and eukaryotic hosts Pichia pastoris) is possible [35-37]. However, initial trials to express IwHNL in E. coli were hampered by formation of inclusion bodies [36]. 

Very interestingly, all cyanohydrins (61h-m) which are substituted with one phenyl group and one less bulky alkyl group or hydrogen atom do not form inclusion complex with 4. However, the cyanohydrins which are substituted with two alkyl groups (62a-c) or with one alkyl group and one hydrogen atom (62d-f) formed complex with 4 and were resolved.27 3... 

Resolution of Ketones. Brucine has not been used very extensively for the resolution of neutral compounds. However, in some cases, ketones or ketone derivatives may form diastereomeric inclusion complexes with brucine, providing an opportunity for their resolution. For example, the cyanohydrin of a bicyclic ketone has been resolved by this procedure (eq 10). Following resolution of the cyanohydrin, the ketone was regenerated and determined to be of 94% ee. 

Alcohol and cyanohydrin guests easily form inclusion complexes with brucine host... 

Scheme 7. Examples for Enantiomer Separations by Crystallization with TADDOLs. Besides the original TADDOL (from tartrate acetonide and PhMgX), Toda et al. [44] have often used the cyclopentanone- and cyclohexanone-derived analogs. The dynamic resolution (resolution with in-situ recychng) of 2-(2-methoxyethyl)cyclohexanone was reported by Tsunoda et al. The resolved compounds shown here are only a small selection from a large number of successful resolutions, which include alcohols, ethers, oxiranes, ketones, esters, lactones, anhydrides, imides, amines, aziridines, cyanohydrins, and sulfoxides. The yields given refer to the amount of guest compound isolated in the procedure given. Since we are not dealing with reactions (for which we use % es to indicate enantioselectivity with which the major enantiomer is formed), we use % ep (enantiomeric purity of the enantiomer isolated from the inclusion...

A further finding is that the prop-2-yn-l-ol derivatives 12-14 form crystal inclusions with alkaloids such as brucine and sparteine which readily allowed optical resolution of 12-14 By the same method, the cyanohydrin 15 and the... 

This resolution method was found to be appUcable to some cyanohydrins 15 and secondary alcohols 16. Very interestingly, the racemic cyanohydrins were converted into a pure optically active isomer in almost quantitative yield in the presence of 72 For example, when a solution of racemic l-cyano-2,2-dimethy 1-1-phenyl-propanol 15a) (1.0 g, 5.3 mmol) and 72 (2.1 g, 5.3 mmol) in methanol (2 ml) was kept in an uncapped flask for 24 h at room temperature, a brucine inclusion compound of 94% ee of +yi5a was obtained in quantitative yield, which upon decomposition gave 94% ee of - -)-15 a (1.0 g). Repeating inclusion formation of the 94 % ee containing (ri- )-75a (1.0 g) Avith 72(2.1 g) one more time yielded 100 % ee of (+)-15a [1.0 g, [a]jj -1- 15.9° (c 1.0 in MeOH)]. The process of the complete conversion of racemic cyanohydrin to one enantiomer consists of racemization of cyanohydrin through the equilibrium in Equation 1 and selective inclusion of one enantiomer in brucine... 

KHMDS has been used to effect a-deprotonation of O-sUyl protected cyanohydrins derived from 2-/7-tolylsulfinyl henzalde-hyde followed by trapping of the C-nucleophile with diverse C-electrophiles, providing a powerful alternative approach to cyanohydrins of ketones. The remote 1,4-asymmetric induction was equally effective for either epimer (diastereomer) of the 0-TIPS protected cyanohydrin, and an equimolar mixture of the two epimers was employed. Both KHMDS and LHMDS bases provided the substituted cyanohydrins from reactions with highly reactive electrophiles (ClCOOMe and ClCOMe) in excellent yields and diastereoselectivities (dr > 98 2) (eq 65). The deprotonation induced by KHMDS led to more reactive nucleophiles, shortening the reaction times. Notably, in alkylations of Eschen-moser s salt, and benzyl and allyl bromides, the application of LHMDS instead of KHMDS improved the diastereoselectivity. The stereoselectivity of the alkylations mediated by KHMDS could be increased by the inclusion of the 18-crown-6 ether... 

ABSTRACT. Novel optical resolutions of guest compounds by inclusion complex formation with optically active host compound are reviewed Tertiary acetylenic alcohols, cyanohydrins, and secondary alcohols were resolved by complexation with alkaloids such as brucine or sparteine. Cycloalkanones, 2,3 -epoxycyclohexanones, and some other neutral compounds were resolved by complex formation with optically active diacetylenic diol. Mutual optical resolution of bis-g-naphthol and sulfoxides by complex formation was also reviewed. 

The process of the enantiomerization probably consists of racemization of cyanohydrin through the equilibrium shown in Equation (1) and the selective inclusion of one enantiomer in brucine. 

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