Racemic sulfates

Another possibility to obtain 100% yield of the enantiopure product is to combine the kinetic resolution with an inversion reaction [25, 35, 36]. In this case an enzymatic hydrolysis is followed by a Mitsunobu inversion. It is, however, in fact a three-step reaction with solvent changes between the reactions. Similarly the sulfatase-catalysed enantios elective inversion of a racemic sulfate yields a homo-chiral mixture of alcohol and sulfate. This yields 100% enantiopure product after a second, acid-catalysed hydrolysis step, which is performed in organic solvent/water mixtures [26]. 

Scheme 4.49 Enantioconvergent hydrolysis of racemic sulfate esters using a sulfatase.

Studies of reaction mechanisms ia O-enriched water show the foUowiag cleavage of dialkyl sulfates is primarily at the C—O bond under alkaline and acid conditions, and monoalkyl sulfates cleave at the C—O bond under alkaline conditions and at the S—O bond under acid conditions (45,54). An optically active half ester (j -butyl sulfate [3004-76-0]) hydroly2es at 100°C with iaversion under alkaline conditions and with retention plus some racemization under acid conditions (55). Effects of solvent and substituted stmcture have been studied, with moist dioxane giving marked rate enhancement (44,56,57). Hydrolysis of monophenyl sulfate [4074-56-0] has been similarly examined (58). 

R)-3-Phenoxybutanoic acid and the corresponding butyl (S)-ester were obtained by Burkholderia cepacia lipase-catalyzed enantioselective esterification of the racemic acid with 1-butanol in hexane containing anhydrous sodium sulfate to remove the water produced during the reaction (Figure 6.17) [64]. 

The organic phase is washed with 150 mL of water and the combined aqueous phases are extracted with 300 mL of dichloromethane. The aqueous solution is then carefully treated with 300 mL of 2 N aqueous sodium hydroxide and the mixture is extracted 4 times with 150 mL of methylene chloride. The combined organic extracts are washed with brine, dried over anhydrous sodium sulfate, and filtered. Removal of volatile material under reduced pressure (water aspirator) gives 47-50 g (89-94%) of racemic diamine as a pale yellow solid, mp 81-82°C, lit.4 mp 82°C corr. (Note 10). 

CAS 35523-89-8 63038-80-2 (Racemic mixture) 220355-66-8 (Diacetate salt) 35554-08-6 (Dihydrochloride salt) 63038-81-3 (Sulfate salt)... 

Indeed, it was shown that aposcopolamine was not formed by direct dehydration of scopolamine, but via the conjugate scopolamine O-sulfate generated by a sulfotransferase [127]. This explains the species differences observed, and indicates a mechanism of heterolytic C-0 bond cleavage made possible by the electron-withdrawing capacity of the sulfate moiety. The reaction is also facilitated by the acidity of the departing proton carried by the vicinal, stereogenic C-atom. This acidity also accounts for the facile base-catalyzed racemization of scopolamine and hyoscyamine [128]. 

Fig. 8 Separation of D- and L-proline aFGF peptides using neutral and heparan sulfate-coated capillaries. A racemic mixture of D- and L-proline-containing peptides (130 /rM) were injected (22 nL) and subjected to electrophoresis using 50 mM sodium phosphate buffer, pH 7.4, 20C, and 20 kV. (From Ref. 73.)...

Natural (—)-actinidine (9a) is prepared from nepetalinic acid imide (262) via dichloropyridine (263) 403) and from iridodial (264) via bis (2,4-dinitrophe-nyl)hydrazone 404) or treatment with ferric ammonium sulfate (Scheme 19) 405). (+)-Actinidine (9b), the enantiomer of natural alkaloid, is synthesized from acid chloride 265, derived from (+)-pulegone, via vinylketone 267 (Scheme 20) 406). Racemic actinidine (9) is prepared by intramolecular cycloaddition of an acetylene across a pyrimidine ring in 5-(hept-5-yn-2-yl)-4,6-dihydroxypyrimidine (268) followed by chlorination and hydrogenation (Scheme 21) 407). 

Aminothiazolines are usually prepared by the acid catalysed cyclization of AT-(2-hydroxyethyl)thioureas or the cyclization of the hydrogen sulfate of thioureas in aqueous basic conditions. These methods give low yields of 2-aminothiazolines and are not suitable for acid sensitive or racemization prone substrates. Mitsunobu reaction of thioureas such as 33 afforded 2-methylaminothiazolines 34 in good to excellent yields <99TL3125>. 

A) is cis- or rran5-CH,CH=CHCH, or H2C=CHCH2CH, (B) is rac-CH CHOHCHjCH,. The intermediate CH,C HCHjCH, can be attacked from either side by HSO to give an optically inactive racemic hydrogen sulfate ester which is hydrolyzed to rac-2-butanol. 

A limitation on resolution is that the desired enantiomer is only half of the racemic starting material. Kurt Faber of the University of Graz has reported (Org. Lett. 2004,6,5009) a clever solution to this problem. On exposure of the sulfate 1 of a secondary alcohol to aerobically grown whole cells of Sulfolobus acidocaldarius DSM 639, one enantiomer of the sulfate was smoothly converted into the other enantiomer of the starting alcohol. The enzyme consumed the more reactive enantiomer > 200 times more rapidly than the less reactive enantiomer. For the last bit of conversion, the of the product alcohol will of course fall. One solution to this would be to run the reaction near 50% conversion, then hydrolyze the mixture to give high product alcohol 2. Exposure of the mixture to a lipase that selectively acetylated the minor enantiomer would then polish the of 2. 

Representatives of all kinds have been explored for synthetic applications while mechanistic investigations were mainly focussed on the distinct FruA enzymes isolated from rabbit muscle [196] and yeast [197,198]. For mechanistic reasons, all DHAP aldolases appear to be highly specific for the donor component DHAP [199], and only a few isosteric replacements of the ester oxygen for sulfur (46), nitrogen (47), or methylene carbon (48) were found to be tolerable in preparative experiments (Fig. 7) [200,201], Earlier assay results [202] that had indicated activity also for a racemic methyl-branched DHAP analog 53 are now considered to be artefactual [203]. Dihydroxyacetone sulfate 50 has been shown to be covalently bound via Schiff base formation, but apparently no a-deprotonation occurred as neither H/D-exchange nor C-C... 

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