Threonine-derived oxazolines

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. 

Wipf and co-workers developed an efficient one-pot process to prepare a variety of highly functionalized 2-substituted 4-oxazolecarboxylic acid esters 39. The starting (3-hydroxyamides 1588 were cyclodehydrated using Deoxo-fluor (bis(2-methoxyethyl)aminosulfur trifluoride) or DAST (diethylaminosulfur trifluoride) to afford intermediate oxazolines 38, which were oxidized in situ with B1CCI3/ DBU to afford 39 (Scheme 1.404). DAST was found to be preferable with serine-derived p-hydroxyamides, whereas Deoxo-fluor was more useful for threonine derived p-hydroxyamides. 

Reaction of furyllithium (60) with L-threonine derived lithium salt 61 afforded the expected ketone 62 in 30% yield. Reduction of 62, using lithium aluminium hydride, gave two alcohols (63 and 64) in a 3 1 ratio. In both carbinols (63 and 64) the oxazoline ring was opened by acid hydrolysis to give the N-benzoyl derivatives 65 and 66, respectively. Alcohol 66 can be used in the synthesis of lincosamine enantiomer, but unfortunately this approach has limited preparative value because of the low yield obtained in the condensation step and, on the other hand, opposite diasteroselectivity obtained in the reduction reaction. 

Employing the Mitsunobu reaction with diisopropyl azodicarboxylate and triphenyl-phosphine, aminoacylserine (in contrast to aminoacylthreonine) is converted into (ami-noacyl)oxazolidine-2-carboxylic acid. 54 By the same procedure a/Zo-threonine peptides are converted into the oxazoline derivatives, whilst the threonine peptides are apparently converted into the aziridines in good yields. 86 ... 

Several new ligands containing the oxazoline nucleus were synthesized in enantiopure form. Compounds of general structure 165 were obtained from L-serine or L-threonine and found application as catalysts for the zinc addition to aldehydes <03TA3292> or were derived from P-amino alcohols and used in diethylzinc addition to A -(diphenylphosphinoyl) imines <03JOC4322>. Also, compound 166 was derived from a commercially available amino acid and afforded good selectivity in allylic alkylation <03TL6469>. 

The cyclamides are small cyclic peptides that characteristically contain multiple thiazole, thiazoline, oxazole, and oxazoline rings, which are derived from cysteine, serine, and threonine residues. Some of the first examples of this class to be described were the patellamides (53-55) from the tunicate Lissoclinum patella, although it was later determined they were produced by the symbiotic cyanobacterium Prochloron sp. The structures were solved by a combination of acid hydrolysis and GC analysis, coupled with 2D NMR. Smaller cyclic peptides from this class include the hexapeptides westiellamide (56) and microcyclamide (57) from M. aeruginosa Many members of the class possess cytotoxic properties, although their biological function or mechanism of action is not fully understood. In contrast to many cyanobacterial peptides, aside from the unusual heterocyclic residues, these peptides generally contain only ribosomal amino acids. 

Also carbanions of serine and threonine esters, protected in the form of oxazolines, are capable of addition to nitropyridines to form the corresponding adducts that can be oxidized into a-(nitropyridyl) amino acid derivatives [132]. It should be mentioned that addition of the carbanion of the protected threonine to nitropyridine proceeds with a high diastereoselectivity, which is controlled by the second chiral center present in the oxazoline ring (Scheme 38) [133],... 

The starting material for this synthesis is the highly substituted achiral naphthalene (34), whose preparation is not given here. The ester group of (34) reacts with the chiral amino alcohol (35) derived from threonine to give the oxazoline (36), which reacts with aryllithium (37) diastereoselectively, affording dihydronaphthalene (38) as a 92 8 mixture of diastereomers. The alkoxy group on the auxiliary is presumed to deliver the nucleophile by chelation to the metal as shown opposite. 

Some amino-sugar syntheses have begun with chiral amino-acids. The four isomeric methyl 2,4,6-trideoxy-4-C-methyl-4-trifluoroacetamido-L-hexopyranosides have been synthesised from L-threonine. The L-ribo-isomer (43) was obtained from the known oxazoline derivative (44) by a ten step procedure (Scheme 17). Grignard... 

Jaroch, S., Matsuoka, R.T., and Overman, L.E. (1999) Studies towards a total synthesis of sarains A-C. Stereospecific condensation of a.P Unsaturated esters with the phenyl oxazoline derivative of threonine. Tetrahedron Lett., 40,1273-1276. 

Y) Oxazolinone formation from P-hydroxyamino acids leads to unsaturated oxazolinones owing to simultaneous elimination of the P-substituent. Erlenmeyer 117) described the formation of 2-methyl-4-benzylidene-oxazolinone by the reaction of phenylserine with acetic anhydride. Carter et al 92, 93, 94) obtained 2-phenyl-4-ethylidene-oxazolin-5-one from N-benzoylthreonine, N-benzoylallothreonine, and their 0-methyl, 0-acetyl and 0-benzoyl derivatives by treatment with benzoylchloride in pyridine. Trifluoroacetic anhydride converts threonine into 4-ethylidene-2-trifluoromethyl-2-oxazolin-5-one 20). 

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