Racemate, cleavage

More recently, the 2-(trifluoroacetyl)vinyl group (4,4,4-trifluoro-3-oxobut-l-enyl, 126) was proposed for the N-protection of amino acids.This enamine derivative is readily prepared with 4-ethoxy-l,l,l-trifluorobut-3-en-2-one and NaOH at room temperature in 1-3 hours. Acidic workup leads to the protected amino acids in yields ranging from 70-89% without racemization. Cleavage is achieved with 3 M HCl in dioxane at room temperature in 10 hours. 

The necessary (i )-(+)-p-chlorophenethylamine is obtained from racemic p-chlorophenethylamine by racemic cleavage with optically active (S)-phenylcarbamate-lactic acid. 

Peptide hydrazides are readily converted to the corresponding acylazides by the action of alkyl nitrites and under appropriate conditions these activated species can be among the least susceptible to racemization. Cleavage of the peptide from the resin as the hydrazide is most useful with protected molecules, which can subsequently be used in fragment condensation to assemble longer peptides. 

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). 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

The (racemic) tmns disulfoxide of 1,3-dithiolane 59 is readily deprotonated at C2 by lithium hexamethyldisilazide, and the resulting anion reacts with aldehydes at -78°C with moderate to excellent diastereoselectivity to give mainly the products 60, although subsequent cleavage of these to give the a-hydroxyaldehydes was not described (97JOC1139). 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

The L-threonine (EC 4.1.2.5), D-threonine (EC 4.1.2.-) or L-allothreonine aldolases (EC 4.1.2.6 synonymous to S1IMT) can be used for resolution of racemic (allo)threonine mixtures by highly selective cleavage of the unwanted isomers42, but can also efficiently direct the anabolic pathways. The substrate spectrum includes propanal, butanal and dodecanal43. 

The alkoxycarbonyl group activates the N — N bond, so that a racemization-free reductive cleavage by treatment with a large excess of lithium in liquid ammonia is possible (sec procedure below). This method is not suitable for hydrazines containing a benzylic C-N bond, because it is cleaved under the reducing conditions. 

The dissolving metal reduction is not suitable, because it effects a cleavage ol the benzylic C-N bond. b The cleavage of the N-N bond by hydrogenolysis is affected by some racemization. 

The original procedure for the trifluoroacetylation of amino acids used trifluoroacetic anhydride [Acetic acid, trifluoro-, anhydride].4 This reagent, although inexpensive and readily available, has certain disadvantages it is a highly reactive compound and thus has caused undesired reactions such as the cleavage of amide or peptide bonds,5 unsymmetrical anhydrides are formed between the newly formed A-trifluoroacetylamino acids and the by-product trifluoroacetic acid, and excess trifluoroacetic anhydride has caused racemization of asymmetric centers. 

In a recent total synthesis of the novel neurotrophic agent merrilactone A (22, Scheme 4) by Inoue and Hirama [24], key intermediate 21 with the cis-bicyclo[3.3.0] octane framework embedded within the caged pentacycle 22 was elaborated from cyclobutane 18 by a sequence of RCM and immediate cleavage of the resulting bicyclic vicinal diol 19 to raeso-diketone 20. Cyclooctenedione 20 then underwent regioselective transannular aldol reaction at low temperature (LHMDS, THF, -100 °C) to produce a 3 1 mixture of isomers in 85% combined yield. The major isomer 21 with the required stereochemistry was then converted into the racemic natural compound ( )-22 in 19 steps. 

In this chapter, DKRs will be categorized according to the racemization method employed, as being catalyzed by (i) a metal, (ii) a base, (hi) an acid, (iv) an aldehyde, or (v) an enzyme. Also racemizations that take place through continuous cleavage/ formation of the substrate, or through 5 2 displacement, among other methods, will be discussed. In most cases, the racemization method of choice depends on the structure of the substrate. In all cases, the KR is catalyzed by an enzyme. 

Racemization through Continuous Reversible Formation-Cleavage of the Substrate... 

However, even planar carbanions need not give racemization. Cram found that retention and even inversion can occur in the alkoxide cleavage reaction (12-39) ... 

For practical reasons, the best scenario is associated with spontaneous substrate racemization. This is often the case for compounds possessing a-stereogenic center bearing an acidic proton adjacent to an activating carbonyl group. When this process is too slow, the substrate must be modified or racemization can be achieved by a reversible cleavage of covalent bonds such as the cleavage of cyanohydrins. 

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