Ethanolamine. chiral

Several recent articles describe the ring-opening of chiral epoxides under microwave irradiation conditions (see also Scheme 6.103). In the context of the preparation of novel /32-adrenoceptor agonists related to formoterol and salmeterol, Fairhurst and a team from Novartis have described the synthesis of chiral ethanolamines by solvent-free microwave-assisted ring-opening of a suitable chiral epoxide precursor with secondary benzylated amines (Scheme 6.129) [262]. At 110 °C, the reaction occurred... 

Dialkylalkoxyborane 29 is treated with ethanolamine to liberate homoallylic alcohol 7 - this work-up allows the recycling of the chiral auxiliary.13 After precipitation of the (IPC)2B-ethanolamine adduct 30 it can be transformed into the allylating agent 27 via compound 31. 

Indium mediates a highly enantioselective Barbier-type allylation of both aromatic and aliphatic aldehydes, using a chiral ethanolamine auxiliary, readily recoverable by acid extraction.193 Barbier coupling of aldehydes can be carried out in water using tin(II) chloride, with cobalt(II) acetylacetonate as catalyst.194... 

The hydroxynitrile lyase (HNL) class of enzymes, also referred to as oxynitrilases, consists of enzymes that catalyze the formation of chiral cyanohydrins by the stereospecific addition of hydrogen cyanide (HCN) to aldehydes and ketones (Scheme 19.36).275 279 These chiral cyanohydrins are versatile synthons, which can be further modified to prepare chiral a-hydroxy acids, a-hydroxy aldehydes and ketones, acyloins, vicinal diols, ethanolamines, and a- and P-amino acids, to name a few.280 Both (R)- and (.S )-selective HNLs have been isolated, usually from plant sources, where their natural substrates play a role in defense mechanisms of the plant through the release of HCN. In addition to there being HNLs with different stereo-preferences, two different classifications have been defined, based on whether the HNL contains a flavin adenine dinucleotide (FAD) co-factor. 

Of examinations with commercially available chiral monoalkylamines and ethanolamines, complexation of chiral acerand 53 (RRRR and SSSS having four chiral carbons of R and S configurations, respectively) and norpseudoephedrine 63 (having two chiral carbons of. -configuration) in chloroform is shown as a representative example in Fig. 16. The (SSSS)-53 63 complex reveals a higher intensity of the absorption maximum near 550 nm compared to that of (RRRR)-53 63. This means that norpseudoephedrine is more easily accommodated in the cavity of (SSSS)-53 than that of (RRRR)-53, in accord with CPK molecular model examinations. 

The ability of pyruvate decarboxylase from many microbial sources to produce phenylacetylcarbinol has been exploited for many years in the synthesis of ephedrine, a natural adrenergic compound (92). The acyloin is reductively aminated to produce the ethanolamine product, (1R,2S)-ephediine, with two chiral centers. 

Scheme 39 shows the procedures of chemical derivatization of the chiral phosphomonoesters analyzed by the 31P NMR method. The procedures for phosphopropane-1,2-diol (55), 5 -AMP (67), 5 -dAMP (70), 3 -TMP (73), and glucose-6-phosphate (76) all involve a cyclization step (with inversion of configuration at phosphorus), followed by methylation or ethylation. The dipal-mitoylphosphatidic acid (79) was first converted to dipalmitoylphosphatidyl-ethanolamine (135), which was then silylated and analyzed by 31P NMR (136). 

Of several active monoalkylamines and ethanolamines, a selective coloration with norpseudoephedrine, Ph(OH)CH—CH(NH2)CH3, is described as a typical example. The examination with CPK molecular models shows that norpseudoephedrine 27 having the -configuration may form a more stable complex with (5555)-dye 4, compared to that with (RRRR)-dyQ 4. In fact, (RRRR)-4 in chloroform was kept yellow by addition of the amine in a range of concentrations, 4.8 x 10 to 1.2 X 10 M, whereas (5555)-4 revealed a color change of the solution from yellow to reddish violet with the same concentration of the amine (Figure 7). We also observed a few examples of enantiomer selective coloration with optically active amines and some chiral dyed crowns as shown in Table I. Further study with various amines is now in progress. 

The 2-amlno-2-deoxy-altrose derivative (2) was the sole product. Isolated in 11% yield, from diaxlal ring opening of the allo-epoxide (3) with ethanolamine, whereas in the synthesis of chiral crown ethers the bulkier N-nucleophile gave a mixture of 2- and 3-amino-... 

The 3,5-disubstituted morpholine derivatives have been obtained in good yield and as a single stereoisomer using a carboamination reaction starting from a chiral a-amino alcohol precursor. In this approach, 2-subsituted (9-allyl ethanolamine 59 has been synthesized from A -Boc-pro-tected amino alcohol by simple (9-allylation, Boc-deprotec-tion, and Pd-catalyzed A -arylation reactions. For substrate 59 when treated with an external aryl bromide and Pd(OAc)2 catalyst in the presence of NaOt-Bu base and... 

The vast majority of the stereochemical studies that have been performed to date are those of enzymes that utilize a nucleotide as a substrate. However, Bruzik and Tsai reported the synthesis of the diastereomers of phosphatidylethanolamine that are chiral by virtue of substitution with 0 and 0 (Bruzik and Tsai, 1982). Their route to the desired product involves the acid-catalyzed hydrolysis of a five-membered ring cyclic phosphoiami-date, which directly yields the ethanolamine moiety on P—N bond cleavage the steps in the synthesis are shown in Fig. 5. dearly, this synthetic strategy is relatively inflexible as to the types of phospholipids that are directly accessible, but the known abihty of phospholipase D to catalyze a facile transphosphorylation reaction (with retention of configuration) does increase the number of chiral phospholipids that can be synthesized. 

In 1965 the first procedure for the asymmetrical synthesis of ethanolamines via enzyme-catalyzed addition of hydrogen cyanide to aldehydes, followed by reduction with LiAlH4 was described [47,137]. Subsequently, in order to avoid decomposition and racemization, TBS-protected cyanohydrins were used [128]. Surprisingly, quantitative deprotection by an intramolecular reductive cleavage occurred and free ethanolamines were obtained in high yields [128,131]. TBS-protected ethanolamines (with one chiral center) could be obtained by DIBAL reduction at low temperature, followed by NaBH4 reduction [124] (Scheme 14). 

Besides the use of stereoselective nitrile-converting enzymes as described above, useful chiral building blocks have also been obtained by stereoselective nitrile-forming enzymes. The main product class of nitrile-forming enzymes are cyanohydrins (a-hydroxynitriles, 1-cyanoalkanols), which are versatile synthons in organic synthesis that are readily convertible to a-hydroxy acids [90], a-hydroxy aldehydes [91], ethanolamines [92], amino alcohols, pyrethroid insecticides [93], imidazoles, and heterocycles [94]. Examples of valuable bioactive products derived from chiral cyanohydrins are (i )-adrenaline, L-ephedrin, and (5)-amphetamines [95]. For the synthesis of chiral cyanohydrins, stereoselective enzymes from both plant and bacterial sources have been used. 

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