Sequential resolution

The results for our kinetic resolutions are shown in Table III. The biphasic procedure was used to synthesize enantiomerically pure aldols by kinetic resolution on a scale of miligrams to grams, with amounts of antibody binding sites ranging from 0.0086 to 0.12 mol %. To illustrate the potential for catalyst recycling, we chose to synthesize (S)-47 via three sequential resolutions of aldol rac-47 with the same 84G3 catalyst. 

The sequential resolution of proteins by charge and mass can achieve excellent separation of cellular proteins (Figure... 

The same method has been applied to the resolution of other 1,2-diols [241,242] as depicted in Scheme 54. For instance, the resolution of 1-benzylglycerol [241], when achieved, should lead to an important chiral synthon of general interest in asymmetrical synthesis and the above-described sequential resolution procedure can afford the enan-tiomerically pure monoacetate. 

The sequential resolution approach has also been used in combined hydrolysis-esterification reactions with Mucor miehei lipase [147] (Scheme 19). This is possible due to the biocatalyst displaying the same stereochemical preference in both hydrolysis and acyl... 

In view of the more complicated reaction systems used today for various reactions involving lipases, it is of fundamental importance to fully understand them in order to correctly interpret experimental results and the influence of various reaction parameters on the enantioselectivity. A very useful tool is therefore to illustrate the different situations of competing species by using the kinetic scheme as exemplified in Scheme 21. This scheme is based on the previously discussed cases of sequential resolutions of an ester bearing a chiral alcohol moiety in Schemes 19 and 20, and shows both the complexity around the free enzyme, where six species compete, and around the two different acyl enzymes, where three nucleophiles compete. 

ScheiTIG 21 A kinetic scheme for the sequential resolution of an acyl donor containing a chiral alcohol moiety according to Schemes 19 and 20. 

In the aqueous phase enzymatic hydrolysis of racemic IPGA leads to IGP (mainly one enantiomer), which can be extracted into the supercritical fluid. Buffering of the pH in the aqueous solution is necessary to provide optimal conditions for the enzyme. In the following lipase-catalyzed esterification IPG reacts with vinyl but) to IPG-butyrate (lipase was from P. cepacia). In this sequential resolution of racemates no processing of intermediates is necessary both reactions take place in different phases (Fig. 19). 

Quadmpole mass spectrometers (mass filters) allow ions at each m/z value to pass through the analyzer sequentially. For example, ions at m/z 100, 101, and 102 are allowed to pass one after the other through the quadmpole assembly so that first m/z 100 is transmitted, then m/z 101, then m/z 102, and so on. Therefore, the ion collector at the end of the quadmpole unit needs to cover only one point or focus in space and can be placed immediately behind the analyzer (Figure 30.1). A complete mass spectram is recorded over a period of time (temporally), which is set by the voltages on the quadmpole analyzer. In this mode of operation, the ions are said to be scanned sequentially. The resolution of m/z values is dependent solely on the analyzer and not on the detector. The single-point collector is discussed in detail in Chapter 28. 

In the scanning (or microprobe) mode the image is measured sequentially point-bypoint. Because the lateral resolution of the element mapping in scanning SIMS is dependent solely on the primary beam diameter, LMISs are usually used. Beam diameters down to 50 nm with high currents of 1 nA can be reached. 

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. 

Jacobsen has utilized [(salen)Co]-catalyzed kinetic resolutions of tenninal epoxides to prepare N-nosyl aziridines with high levels of enantioselectivity [72], A range of racemic aryl and aliphatic epoxides are thus converted into aziridines in a four-step process, by sequential treatment with water (0.55 equivalents), Ns-NH-BOC, TFA, Ms20, and carbonate (Scheme 4.49). Despite the apparently lengthy procedure, overall yields of the product aziridines are excellent and only one chromatographic purification is required in the entire sequence. 

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

Scheme 7.22 Mechanism of the sequential kinetic resolution of trans-cyclohexane-1,2-diamine.

Figure 12. Cross-sectional TEM images of a silica sample implanted with Ag and S (a) high-resolution image showing the lattice planes of the Ag2S shell (b) bright-field showing the contrast between the Ag core and the Ag2S shell (c) and (d) are the diffraction pattern of the sample sequentially implanted with S followed by Ag and with Ag followed by S, respectively. (Reprinted from Ref [1], 2005, with permission from Italian Physical Society.)...

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