Amino alcohol moiety

The 10 OC route was followed for the synthesis of tetrahydrofurans possessing a y-amino alcohol moiety 247 (Eq. 29) 118]. Aldoximes 21a-f (see also Eq. 3 and Table 2), when heated in benzene in a sealed tube at 110 -120 °C for 6 h, underwent smooth intramolecular cycloaddition to the tetrahydrofuranoisoxazo-lidines 246a-f in 70-83% yield (Eq. 29). This ring closure proceeded stereo-specifically to generate three adjacent stereogenic centers. LAH reduction of 246 b resulted in isolation of stereospecifically functionalized tetrahydrofuran derivative 247b in 75% yield. 

For carboxyl terminal determination of peptides by means of CDI the terminal carboxylic acid group of the peptide is selectively reduced with sodium dihydrobis(2-methoxy-ethoxy)aluminate to an alcohol. Subsequent conversion of the amino alcohol moiety with CDI yields an 7V-acyl-2-oxazolidone derivative, from which the oxazolidone unit can be easily removed and characterized.[56]... 

The reductive cleavage of the N-O bond in the isoxazolidine 162 unmasks the 1,3-amino alcohol moiety. Thus, isoxazolidines can be viewed as direct precursors of 7-amino alcohols. The reductive cleavage of the cycloadduct proved difficult. W2 Raney-Ni and nickel boride were both ineffective. In contrast, nickel-aliminium alloy in an alkaline medium efficiently reduced the N-O bond at room temperature in the presence of a base (Equation 27) <1997TA109>. 

Replacing the rigid proline core with a more flexible pipecolinic acid, as in 83, led to an increased selectivity (Table 7.7, entry 3) [79]. However, a real improvement was attained with catalysts 84a,b, where 1,2-diphenylamino ethanol derivatives were used instead of aniline to form the amide (entries 4 and 5). Configuration at the a-carbon of the amino alcohol moiety proved to be critical in forming the matched pair (compare entries 4 and 6), while configuration at the /Tcarbon bore no influence on the enantioselectivity (compare entries 4 and 5). 

Stereoselective synthesis of the 1,3-amino alcohol moiety is possible starting from N-tert-butyldimethylsilyloxycarbonyl derivatives of allylic halides 5 through a ScN cyclization. Thus, methyl ( )-2-tm-butyldimethylsilyloxycarboiiylamino-6-chloro-4-hexenoatc (5, R = COOCH3), treated with 2 equivalents of silver fluoride in acetonitrile, gives a mixture of the cis- and trans-tetrahydro-2//-l,3-oxazin-2-oncs 6 in 65% yield, although in moderate diastereoselectivity,9c. 

Initial studies [26] carried out with enol carbonates A or P-keto esters B afforded ketones D in high yields and selectivities up to 75% ee [27], using ephedrine or a P-amino alcohol derived from camphor. Surprisingly, cinchona alkaloids bearing the required P-amino alcohol moiety were not tested. It was necessary to wait till 2001 and later for publications describing the use cinchona alkaloids in these reactions, either the natural products or some analogues. 

A recently new designed Wang resin supported Evans chiral auxiliary (52) has been shown to perform Evans asymmetric alkylation on solid support (Scheme 12.19) [34, 35], Preparation of the auxiliary started with coupling of Fmoc-piperidine-4-carboxylic acid to Wang resin. Subsequent removal of the Fmoc protection was followed by coupling to N-protected (2J ,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid. After deprotection, the amino-alcohol moiety was converted into the oxazolidinone auxiliary 52 using carbonyldiimidazole (CDI). 

The most characteristic structural feature of these compounds is that the oligosaccharide part is not directly connected to the long-chain, amino alcohol moiety. The connecting group on the long-chain, amino alcohol is a phosphate group, and, on the oligosaccharide part, an inositol residue. 

Davies and coworkers found that streptomycin adenylyl transferase also adenylylates spectinomycin and actinamine. Because of the stereochemical resemblance between actinamine and the o threo methyl-amino alcohol moiety in streptomycin, the site of adenylylation was considered to be that shown by the arrow in formula 15. 

The presence of two stereogenic centers on the amino alcohol moiety with the correct relative configuration such as in (1/ , 25)-(—) ephedrine is necessary to stereodirect the imine attack by trichlorosilane. 

Most of the above examples demonstrate that the amino-alcohol moiety can be synthesised with a high degree of stereocontrol. Furthermore, the formation of heterocyclic intermediates, in particular oxazolidinones and oxazolines above, is often a crucial factor in exercising this control. Hence, ring fragmentations of, -heterocycles, produced by methods other than allylic functionalisation, persist as an important area within amino-alcohol synthesis. 

Amino-alcohol moieties within imino-sugars have been established... 

Optically active halohydrins or styrene oxide derivatives obtained by the reduction of a-halo ketones followed by treatment with base have been widely used as key intermediates in the synthesis of many chiral drugs containing the p-amino alcohol moiety. Examples of such drugs include (R)-denopamine (13) [46a], (R)-isoproterenol (14) [46b], d-solatol (15) [47], (R)-fluoro(nor)epinephrine (16) [48], (R)-salmeterol (17) [49], and (R,R)-formoterol (18) [50] (Scheme 11.4). Most OABs were effective for the reduction of 2-bromo- or 2-chloroacetophenone derivatives (22), providing the corresponding halohydrins with high enantioselectivities (Table 11.4). 

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