Boc-L-threonine

L-Threonine provides two chiral centres for synthetic manipulation, a feature demonstrated in work by Rohl and coworkers [84] directed at confor-mationally constrained inhibitors of ACE and neutral endopeptidase (Scheme 5.27). Nucleophilic substitution of 2-fluoro-l-nitrobenzene with the alkoxide generated from A -Boc-L-threonine, followed by hydrogenation and cyclocondensation gave the key benzoxazepine intermediate (59). An... 

A synthesis of N,N-diprotected L-serinals 1817 [1382] and a straightforward synthesis of N-Boc-L-serinal and N-Boc-L-threoninal acetonides [1383], with a Swern oxidation as the final step, have been reported. Protected L-serinals were synthesized from L-serine by reduction of the methyl esters 1815 followed by Swern oxidation of the corresponding alcohols 1816. 

Akaji and Kiso" reported an efficient synthesis of 1297 (Scheme 1.331) from Boc-(l )-MeCys(Bn)-OH, Boc-Thr(Bn)-NHCH3 and 3-phenylpropionyl chloride. They improved the peptide-coupling conditions for the sterically hindered a-methylcysteine and threonine analogs normally used to prepare 1187 and 1188. 

The starting 2-cinnamyl-4-cyano-4-methylthiazoline 1285 was prepared in three steps from (l )-2-methylcysteine methyl ester hydrochloride 1284 (Scheme 1.329). The synthesis of 1283 was accomplished by condensation of 1284 with 1285, followed by reptition of steps two and three (Scheme 1.329). For 1289 HCl (Ri = CH3), bis-Boc-(/ )-2-methylcysteine, 1286 was coupled with rac-threonine methyl ester hydrochloride followed by cyclization with Burgess reagent to afford a mixture of diastereomeric oxazolines 1288. Oxidation of 1288 with Cu(l)Br/t-butylperbenzoate (Section 1.3.1.4) proved to be more efficient than Ni02. Deprotection then yielded 1289 HCl (Rj = CH3). 

Schmidt and coworkers [16]. Compounds with general structure 5 and 6 were synthesized starting from Boc-protected L- or D-threonine that were lactonized withbenzotriazole-l-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP) and EtgN. Subsequently, the Boc group was cleaved and carboxylates were coupled to provide the products. 

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