Threonine ether

CF3CO2H, PhSCH3, 25°, 3 h. ° The use of dimethyl sulfide or anisole as a cation scavenger was not as effective because of side reactions. Benzyl ethers of serine and threonine were slowly cleaved (30% in 3 h complete cleavage in 30 h). The use of pentamethylbenzene had been shown to increase the rate of deprotection of 0-Bn-tyrosine. ... 

Quaternary salts of the substances represented by tliese formulae have been prepared by Kogl, Veldstra and van der Laan as well as of the next lower homologues, the substituted butyraldehydes, and the methyl ethers of both series. Their pharmacological activities were negligible in comparison with that of muscarine, but as six stereoisomeric forms may be produced in each synthesis, the inactivity may be due to stereoisomerism, just as in the case of threonine (a-amino-)3-hydroxy-butyric acid) where West and Carter found that only the d —) form is... 

These water-sensitive derivatives can be used to form cleanly the t-butyl ethers of serine and threonine. They are cleaved with aqueous acid or base. ... 

To a solution of L-threonine allyl ester hydrochloride [22,42] (6.0 g, 30.6 mmol, the corresponding hydrotrifluoroacetate or hydrotoluenesulfonate can also be used) in saturated NaHCOj solution (100 mL) and dioxane (100 mL) is added dropwise at 0°C a solution of 9-fiuorenylmethyl chloroformate (10.8 g, 41.8 mmol) in dioxane (50 mL). After stirring for 24 h, the solvent is evaporated in vacuo, the remainder dissolved in ethyl acetate (200 mL), washed with 0.5 N HC1, saturated NaHCOj solution, and water (each 100 mL), dried with MgS04, and concentrated in vacuo. The crude product is subjected to chromatography on silica gel (300 g) in petroleum ether-ethyl acetate (4 1), and the obtained product is recrystallized from ethyl acetate-petroleum ether to give pure 24 yield, 11.2 g (96%) mp 98°-100°C [a]D -17.2° (c 1, dimethylformamide) R, 0.33 (petroleum ether-ethyl acetate 2 1). 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

Vercellotti et al. (65) studied the rates of / -elimination for O-benzyl ethers of O-glycosyl-N-(2,4-dinitrophenyl)-L-serine and L-threonine methyl esters in non-aqueous solvents using various bases. The corresponding acetyl derivatives of 2-acetamido-2-deoxy-D-galactose were also included. Generally, these substances were highly reactive, but the nature of the solvent and the base type were influencing factors. Thus, no elimination occurred in benzene when trimethylamine was used as base. 

COOH O -OH aspartic add glutamic acid tyrosine serine threonine benzyl and t-butyl esters or ethers, resp. PhCHgBn /BF,-Ei,0 HBr/TFA... 

L-Threonine occurs as a white, crystalline powder. It is freely soluble in water, and insoluble in alcohol, in ether, and in chloroform. It melts with decomposition at about 256°. 

Figure 12.3 (A) Mechanism of inactivation of the 20.S proteasome by NPI-0052. (B) Superposition of NPI-0052 (SalA) and salinosporamide B (SalB) in the P5 subunit of the yeast 20.S proteasome. Each inhibitor is covalently bound to the N-terminal threonine (Tl) via an ester linkage between Thr lOy and the carbonyl derived from the P-lactone ring. In the case of NPI-0052, the chlorine atom is displaced to form a five-membered cyclic ether ring.15...

The traditional method for preparing (m-butyl ethers involves reacting a large excess of isobutene with a solution of the alcohol in dichloromethane in the presence of concentrated sulfuric acid, p-toluenesulfonic acid or phosphoric acid and the method is effective for protecting the side chain hydroxyl functions of serine, threonine [Scheme 4.123], and tyrosine.223 224 A more convenient method involving use of Amberlyst H-15 resin in hexane as the acid catalyst deserves wider attention.217... 

Cytochrome P450-catalyzed 4-hydroxylation, followed by formation of an ether bond to the hydroxyl group of tyrosine, threonine or serine, or a thio-ether bond to the sulfhydryl group of cysteine (Figure 2.8). 

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