Serine hydroxy groups

To allow for the use of the stronger sulfating reagent pyridine/S03, an alternative protection strategy has been proposed by Fujii et al. 55-99 that is based on postsynthetic protection of the amino groups as Fmoc derivatives and of the serine hydroxy groups as terf-butyldiphenylsilyl derivatives as shown in Scheme 12. The histidine side chain is not protected since model studies indicate that sulfated histidine is readily hydrolyzed by water within 60 minutes. 

There are two forms of the enzyme, phosphorylase a and the less active form phosphorylase b. Phosphorylase a is an oligomeric protein with four major subunits. Phosphorylation of a serine hydroxy-group produces an active form of the enzyme. Removal of the phosphate causes a breakdown of the tetramer to a dimeric form which is the less active phosphorylase b. Re-activation is achieved by the enzyme phosphorylase kinase which catalyses the phosphorylation at the expense of ATP. 

Despite the relatively high reactivity of the serine hydroxy group, serine esters and serine-containing peptides with free hydroxy groups have been used as amine components in solution synthesis. Syntheses with free serine hydroxy groups can be performed with azides, without the risk of 0-acylation.b l Mixed anhydrides, active esters, and carbodiimides have also been successfully used for the coupling reactions. Therefore, for this couphng reaction, any over activation has to be avoided. 

The earliest method developed for the preparation of nonracemic aziridine-2-car-boxylates was the cyclization of naturally occurring (3-hydroxy-a-amino acid derivatives (serine or threonine) [4]. The (3-hydroxy group is normally activated as a tosyl or mesyl group, which is ideal for an intramolecular SN2 displacement. The cyclization has been developed in both one-pot and stepwise fashion [4—9]. As an example, serine ester 3 (Scheme 3.2) was treated with tosyl chloride in the presence of triethylamine to afford aziridine-2-carboxylate 4 in 71% yield [9]. Cyclization of a-hydroxy- 3-amino esters to aziridine-2-carboxylates under similar conditions has also been described [10]. 

Figure 6.1 Synthesis and metabolism of acetylcholine. Choline is acetylated by reacting with acetyl-CoA in the presence of choline acetyltransferase to form acetylcholine (1). The acetylcholine binds to the anionic site of cholinesterase and reacts with the hydroxy group of serine on the esteratic site of the enzyme (2). The cholinesterase thus becomes acetylated and choline splits off to be taken back into the nerve terminal for further ACh synthesis (3). The acetylated enzyme is then rapidly hydrolised back to its active state with the formation of acetic acid (4)...

Catalytic site of lipase is known to be a serine-residue and lipase-catalyzed reactions are considered to proceed via an acyl-enzyme intermediate. The mechanism of lipase-catalyzed polymerization of divinyl ester and glycol is proposed as follows (Fig. 3). First, the hydroxy group of the serine residue nucleophilically attacks the acyl-carbon of the divinyl ester monomer to produce an acyl-enzyme intermediate involving elimination of acetaldehyde. The reaction of the intermediate with the glycol produces 1 1 adduct of both... 

Silk fibroin contains no cystine and the content of lysine and histidine is also low (about 1% in total), but it does contain tyrosine phenolic (13%) and serine alcoholic (16%) sidechains. Since glycine accounts for 44% of the total aminoacid content, an N-terminal glycine residue is reasonably representative of most of the primary amino dyeing sites in silk fibres. Amino acid analysis of hydrolysed reactive-dyed silk indicates that the reaction between fibroin and reactive dyes takes place mainly at the e-amino group of lysine, the imino group of histidine and the N-terminal amino group of the peptide chain. In an alkaline medium, the hydroxy groups of tyrosine and serine also react [114]. 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

Transvalencin Z (245a) from Nocardia transvalensis could be a precursor or side product of mycobactin biosynthesis, possibly acquired from a vagabonding gene. It comprises the left part of the serine/salicylic acid based molecules (Table 5 R" = = H) and ends with A/ -formyl-Lys (R = H, no iV-hydroxy group). The... 

A comparison of direct O-mannosylation of serine or threonine on resin-bound peptides, with the incorporation of mannosylated serine or threonine building blocks, resulted in a higher overall yield for the building block approach (12.5 vs 5% for direct condensation). 134 Later it was demonstrated that resin-bound peptides are able to be glycosylated with different glycosyl trichloroacetimidates without protection of the hydroxy groups of the oligosaccharide moiety (Section 6.3.2.8). 135,136 ... 

Access to the imino group of oxazolidine-4-carboxylic acid is even more sterically hindered when substitutions are performed at the C2 position. For such cases, the typical procedure is based on the conversion of the desired serine or threonine dipeptides with unprotected hydroxy groups into the oxazolidine rings by reaction with aldehydes or ketones,1139,1691 as described in Vol. E 22a, Section 2.3.2.4. 

Serine proteases. The ft- hydroxy group of serine acts as a nucleophile under slightly alkaline conditions examples are trypsin, chymotrypsin, and subtilisin. 

The hydroxy group of L-serine methyl ester does not undergo reaction with the activated ester 49 because of its smaller nucleophilicity. 

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