Threonines derivatives

C-N.m.r. Chemical-shift Data for Various a- and /i-D-Clycosyl-L-threonine Derivatives... 

The stereochemistry in the electrochemical oxidation of (96) yielding N, O-acetals (98) is of timely interest. The electrochemical oxidation of acyclic threonine derivative... 

Scheme 39 Diastereoselective anodic decarboxylative substitution of a threonine derivative.

Ketone donors bearing a-heteroatoms are particularly useful donors for the enamine-catalyzed aldol reactions (Scheme 18). Both anti and syn aldol products can be accessed in remarkably high enantioselectivities using either proline or proline-derived amide, sulfonamide, or peptide catalysts. The syn selective variant of this reaction was discovered by Barbas [179]. Very recently, Luo and Cheng have also described a syn selective variant with dihydroxyacetone donors [201], and the Barbas group has developed improved threonine-derived catalysts 71 (Scheme 18) for syn selective reactions with both protected and unprotected dihydroxyacetone [202]. 

The reaction generally tolerates steric hindrance at the 2-exocyclic position as well as at the 4- and 5-positions. However, the reaction rate was found to be sensitive to steric effects. Thus, thiolysis of a threonine-derived oxazohne 332 was considerably slower than that for the corresponding serine-derived oxazoline 333 (Scheme 8.101). The rate difference could be exploited to selectively convert a serine-derived oxazoline to a thioamide in the presence of a threonine-derived oxazoline. 

However, this strategy failed when applied to the synthesis of the cyclopeptide lissoclinamide 7. Here, the serine-derived oxazoline moiety could not be selectively thiolyzed in the presence of the threonine-derived oxazoline in the cyclopeptide 334. " The authors attributed this lack of chemoselectivity to the increased stability and thus reduced reactivity, of the serine-derived oxazoline in the macrocyclic scaffold. AU three oxazoline moieties reacted under the prolonged reaction conditions to give the trithio cyclopeptide 335 (Scheme 8.102). The structure of 335 was confirmed by conversion to the tristhiazoline cyclopeptide 336. 

S,3R). Secondly, the t/treo-3-methyl-D-cysteine (25,35) was prepared using the previously described addition of thiocarboxylic acid to threonine-derived aziridines. 62 ... 

Contrary to this finding, the enolate of the threonine derivative 12 is alkylated in about 90% yield and with >95% diastereoselectivity to give the expected isomer 1376-79. 

A group at the Academy of Sciences in Moscow 197) has synthesized chiral threonine. Derivatives of cyclic imino acids form copper complexes with glacine and carbonyl compounds. Hydroxyethylation with acetaldehyde and decomposition of the resulting complexes produced threonine with an optical purity of up to 97-100% and with threo/allo ratios of up to 19 1 197). The chiral reagents could be recovered and re-used without loss of stereoselectivity. The mechanism of this asymmetric synthesis of amino acids via glacine Schiff base/metal complexes was also discussed 197). 

Other N-protected threonine derivatives as well as N-protected serine derivatives can be converted to the corresponding (erf-butyl esters using this method [34]. 

Glycosylation of a Threonine Derivative Suitable for Glycopeptide Synthesis [55]... 

The methyl ester 84 was dissolved in a Na2C03 soln (dioxane/H20 2 1) at 0°C and treated with Boc20 according to standard literature protocol 135 to give the threonine derivative 90 as an oil (yield 86%), which was used without further purification in the next step. 

Support-bound, enantiomerically pure alcohols can be converted into phosphonates by Mitsunobu esterification, which results in complete inversion at the stereo-genic center. This strategy has been used to prepare peptidyl phosphonates on solid phase. These are interesting transition-state analogs with potential utility as peptidase inhibitors (Figure 11.3 [12,13]) or tyrosine phosphatase inhibitors [14]. Serine or threonine derivatives can be converted into phosphonates by direct phosphonylation with an activated monoalkyl phosphonate [15] or by treatment with phosphonamidites RP(OR)NR2 in the presence of tetrazole followed by oxidation [16]. 

As Scheme 47 illustrates, the threonine derivative 149 is coupled with 147b to furnish the dipeptide 150, which, after protecting group manipulation and further... 

The intermolecular Diels-Alder reaction between the dibromoenone (111) and dienes (112) provides access to bicyclo[5.4.0]undecane systems (113) that are common core structures of many natural products (Scheme 32).118 The alio-threonine-derived O-(/ -biphenyl carbonyl oxy)-/i-phenyloxazaborolidi none catalyses the enan-tioselective Diels-Alder reaction of acyclic enones with dienes.119 The reversal of facial selectivity in the Diels-Alder cycloaddition of a semicyclic diene with a bro-moenone was induced by the presence of the bromo substituent in the dienophile.120 Mixed Lewis acid catalyst (AlBr3/AIMe3) catalyses the Diels-Alder reaction of hindered silyloxydienes with substituted enones to produce highly substituted cyclohexenes.121 Chiral /V-enoyl sultams have been used as chiral auxiliaries in the asymmetric Diels-Alder reactions with cyclopentadiene.122... 

Asymmetric hydrogenation of racemic 2-substituted (3-keto esters to produce 2-substituted (3-hydroxy esters with two new chiral centers is a powerful method, and it is useful in the production of other pharmaceutical intermediates. The methodology can be used in the preparation of protected threonine derivatives 34, where 34d and 34e are key intermediates for the anti-Parkinsonian agent, L-Dops (35). 

CsA is a cyclic undecapeptide consisting completely of hydrophobic amino acids, as shown in Figure 1.8 [37]. Additional structural features are a threonine-derived butenyl-containing amino acid derivative as well as six N-methylated amino acid residues. In addition to reducing the proteolytic degradation rate and increasing the... 

The synthetic manipulation of O-glycosylamino acid molecules is usually more complex because they may undergo the acid-catalysed anomerisation of glycosidic bonds (Figure 3.3) and they are also usually more sensitive to acid conditions, due to their aldolic nature (e.g. serine and threonine derivatives). However, the acid-sensitivity is modulated by saccharide and peptide nature. 

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