Threonine tert.butyl ester

N-(benzyloxycarbonyl)-L-threonine tert-butyl ester +55 CHCIj 148a... 

The Fmoc group can also be combined with the fert-butyl ester in 0-glycopeptide synthesis [I6,34J. The Fmoc serine and threonine tert-butyl esters with free (3-hydroxyl groups are required as starting materials for this chemistry. These compounds (e.g., the threonine... 

N-(9-Fluorenylmethoxycarbonyl-0-(3,4,6-tri-0-acetyl-2-azido-2-deoxy-OL-n-galactopyranosyl)-L-threonine tert-Butyl Ester 20 [34]... 

TH-0-acetyl-2-azido-2-deoxy-a-D-galactopyranosyl)-L-threonine tert-Butyl Ester 22. A solution of Fmoc-Thr(aAc3GalN3)-OtBu 20 (215 mg, 0.3 mmol) in freshly distilled morpholine (2 mL) is stirred at room temperature for 20 min. After concentration in vacuo and codistillation with toluene (twice 3 mL) in vacuo, 22 is obtained quantitatively. It is immediately used in the following reaction. 

To Fmoc 0-glycosyl threonine tert-butyl ester 20 (290 mg, 0.4 mmol) dissolved in dry dichloromethane (5 mL) is added dry trifluoroacetic acid (3 mL) at 0°C. The mixture is allowed to warm to room temperature, and the reaction is monitored by TLC (dichloro-methane-ethanol 10 1). After 3 h, the conversion is complete. The solvent is evaporated in vacuo. Toluene (10 mL) is codistilled in vacuo from the remainder. Small amounts of an unpolar impurity are separated by flash chromatography on silica gel (20 g) in dichloro-methane-ethanol (15 1) yield 230 mg (90%) [oL 69.7° (c 1, CHCL) R. 0.32 (CH,CL-ethanol 10 1). 

Fmoc-threonine tert-butyl ester 7 to afford the desired fully protected Tn-antigen-threonine conjugate 8 . This conjugate provides the following principal advantages for the further extension of the carbohydrate structure in order to cover all mucin-type tumour-associated carbohydrate antigens 1-5 (Scheme 2) ... 

Paulsen and associates (58) synthesized mono- and di-D-galactopyranosyl derivatives of L-serine/L-threonine. Condensation of the 2-azido-2-deoxy-glycosyl halides 61 and 62 with the benzyl or tert-butyl esters of iV-benzyl-oxycarbonyl (Z)-protected L-serine, L-threonine, and L-leucyl-L-serine (63 -65) in the presence of silver carbonate, silver perchlorate, Drierite, and molecular sieves gave (59) the corresponding O-glycopeptides 67-69. The free glycopeptides were obtained after total deprotection. 

Ring closure of (3-hydroxy-a-amino acids with sulfuryl chloride/triethylamine 68 is accompanied by formation of (3-chloroalanine,16 1 whereas cyclization of urethane-protected serine and threonine by the Mitsunobu reaction 54 69 70 leads to oxazoline and dehydroalanine formation as side products. 47,71 Formation of dehydroalanine can be prevented by bulky carboxy protecting groups such as tert-butyl esters. 69 ... 

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

The acetyl protecting groups stabilize the glycoside bonds towards acids. Thus, the tert-butyl ester can be cleaved with trifluoroacetic acid (TFA) to give the Tn-threonine building block 9. 

An alternative route starting from serine 73 or threonine 68 74 makes use of diethoxy-triphenylphosphorane. Attempts to asymmetrically synthesize (25)-aziridine-2-carboxylic acid (1) by treating a, 3-dibromopropanoates with chiral amines 75 or by the Staudinger reaction from oxirane-2-carboxylic acid ester 70,76 leads to optically impure products, whereas 3-alkyl derivatives of tert-butyl aziridine-2-carboxylates can be prepared with high cis-selectivity from a-halo ester enolates and jV-trimethylsilyl imines. 77 Moreover, when optically... 

---