Serine oxidation with periodate

Dihydroxylation of olefins followed by oxidation with periodate leads to cyclization and the corresponding carbinolamine. This can then be reduced to the piperidine <2005JOC10182> (Scheme 12). The strategy was used in the synthesis of both the (2A,3i )-3-hydroxypipecolic acid 13 and (2 5, 3A)-3-hydroxypipecolic acid 14 from D-serine. Variations in this strategy toward both trans-isomers of the 3-hydroxypipecolic acid moiety are shown in Schemes 13 and 14. The initial stereochemistry was introduced using Sharpless method <2005JOC360>. 

Because of their neighboring amino and hydroxyl groups both serine and threonine can be oxidized with periodate to give formaldehyde or acetaldehyde, respectively. 

Figure 1.106 An N-terminal serine or threonine residue can be oxidized with sodium periodate to produce an aldehyde group. The reaction can be quenched with sodium sulfite to eliminate excess periodate.

This characteristic component of the phytosphingolipids gives L-serine phosphate on oxidation with permanganate and hydrolysis, followed by periodate oxidation. 

The oxidation of tryptophan with periodate under acid, neutral and alkaline conditions has been studied (18, 221, 326). Yields of isolated products were low due to occurrence of deamination and tar formation (78). Products detected (8% yield) include formylkynurenine under neutral conditions and dioxindolylalanine under acid conditions. Traces of serine and aspartic acid were also detected. Oxidation in the presence of ammonia gave the quinazoline (56) previously identified (338) as a photooxidation product of tryptophan. By contrast, indole-3-... 

Unique methods based on new principles have been developed within the past 10 years. Threonine (27,28,249) is oxidized by lead tetraacetate or periodic acid to acetaldehyde, which is determined by photometric analysis of its p-hydroxydiphenyl complex or iodometric titration of its combined bisulfite. Serine is oxidized similarly to formaldehyde, which is determined gravimetrically (207) as its dimedon (5,5-dimethyldihydro-resorcinol) derivative or photometric analysis (31) of the complex formed with Eegriwe s reagent (l,8-dihydroxynaphthalene-3,5-disulfonic acid). It appears that the data obtained for threonine and serine in various proteins by these oxidation procedures are reasonably accurate. [Block and Bolling (26) have given data on the threonine and serine content of various proteins. ]... 

Figure 1.107 The N-terminal aldehyde group on a peptide formed from periodate oxidation of serine or threonine residues can be conjugated with a hydrazide-containing molecule to produce a hydrazone bond.

Hydrolysis of ferrirhodin with HI gives serine, glycine, alanine, ornithine and ammonia in the ratio 0.20 1.00 1.55 2.95 0.02. Alanine is not found on hydrolysis with HC1. Periodate oxidation gives cfs-5-hydroxy-3-methyl-pent-2-enoic acid, isolated as the lactone. Reduction with H2 and palladium charcoal gives hexahydroferrirhodin, identical with hexahydroferrirubin. 

Table VII summarizes the conditions for chymotryptic hydrolysis of the proteins and peptides listed in Table VI. The parameters which would be expected to determine the rate of hydrolysis (apart from the nature of the bonds in the particular substrates) are temperature, pH, time of hydrolysis, and the molar ratio of chymotrypsin to substrate. All these factors often differ considerably for the substrates listed. Hydrolyses have been performed under conditions which vary from 2 to 24 hr, from pH 7.0 to 9.0, from 22° to 40°C, and at enzyme to substrate molar ratios between 1/360 to 1/21. It is not obvious how variations in pH and temperature affect the apparent specificity of chymotrypsin, but at low molar ratios of enzyme to substrate only the most susceptible bonds would be expected to be hydrolyzed. The lowest molar ratio was employed in the studies with ribonuclease. The only bonds of an unusual nature which were split were those formed by serine and histidine in the following sequences, -Thr-Ser. . . Ala-Ala- and -Lys-His. . . Ileu-Ileu-. Many of the unusual splits listed in Table VI were observed in equine or human cytochrome c and in oxidized papain. Each of these substrates was digested for long periods of time and at high ratios of enzyme to substrate under conditions which would be expected to split bonds that are usually resistant to hydrolysis.

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