Phenylserine derivative

Phenylserine derivative (132), precursor to the enantiomer of the antibiotic thiamphenicol, has been prepared with 92% de and >99% ee using a recombinant D-ThrA from Alcaligenes xylosoxidans, whereas the opposite L-configurated isomer was obtained by i-ThrA catalysis with only low diastereoselectivity [196]. 

Another method of obtaining unsaturated azlactones is through p-phenylserine [Ser(p-Ph)] derivatives. This method was initially introduced by BergmannJ56 The method involves conversion of (3-phenylserine derivatives 11 into the corresponding APhe azlactones 12 by treatment with an acetic anhydride/sodium acetate solution (Scheme 4). This has remained as one of the most popular methods of synthesis. 

Nonracemic phenylserine derivatives can be prepared by the addition of ammonia to a,/ -di-halocarboxylic acid esters via aziridines59. Treatment of (li )-menthyl 2,3-dibromo-3-phenyl-propanoate (7) with methanolic ammonia proceeds stereoselectively to give a readily separable mixture of the diastereomeric and thermodynamically more stable (17 )-menthyl a s-3-phenyl-2-aziridinecarboxylates (8A and 8B) as crystalline solids59. 

Lrthreonine aldolase (L-threonine acetaldehyde-lyase) catalyzes the reversible condensation of acetaldehyde and glycine to form L-threonine. The enzyme has been shown to be an activity distinct from serine hydroxy-methyltransferase that also catalyzes the above reaction (85,86). The substrate specifically of the adolase has been demonstrated to be flexible with respect to the aldehyde involved. The enzyme has been shown to form phenylserine derivatives from substituted benzaldehydes and glycine (86). 

Lactams (10, 447-448 11, 589). Cyclization of p-hydroxy aryl amides to p-lactams by a Mitsunobu reaction is stereospecific. Thus the protected derivative 1 of phenylserine cyclizes to 2 as the only p-lactam and an aziridine. The configuration at C, of 1 is retained, whereas the configuration at C., is inverted. 

P-Hydroxy-amino acids (Figure 10.7) are multifunctional compoimds with valuable interest as intermediates for the synthesis of statine derivatives (106) [166-168], protease inhibitors [169], antivirals [170, 171], peptide mimetics [172], idulonic acid mimetics, for example, 3R,5R-dihydroxy-L-homoproline (111) [173], immimosup-pressive lipid mycestericin d (112) [174], 3,4-dihydroxyprolines (113) [175], (2S,3R)-2-amino-3-hydroxybutyrolactone, precursor of monobactam antibiotics [176], or L-ffereo-3-[4-(me ylthio)phenylserine] precursor of thiamphenicol (114), florfenicol (115) [177], sialyl Lewis x mimetics (117) [178], p-hydroxyomithine (109), a relevant building block for the p-lactamase inhibitor, clavulanic acid, and the antibiotic and anticancer acivicin [179], surveyed in previous reviews [41,57]. 

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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