Hydrolysis of DHA

In neutral and alkaline aqueous solutions, DHA is very rapidly hydrolyzed to DKG. If DHA is adjusted to pH 7.0 in buffered solution and immediately assayed by TLC or NMR, only DKG is observed. In unbuffered solution the conversion is slow because hydrolysis of DHA produces an acid, lowering the pH to approximately 2.5. Many of the... 

FIGURE 20.1 Effect of added moisture on the yield of DHA-bound lysophosphatidylcho-line (DHA-LPC) after partial hydrolysis of DHA-bounded phosphatidylcholine (PC) mediated by lipozyme RMIM 20 mg PC, 53 mg lipozyme RMIM, 17.7 MPa pressure, 33°C, 3.0 mL/min SC-CO2 flow rate, 4 h reaction, 10 mL reaction volume. 

FIGURE 20.3 Effect of pressure on the yield of DHA-LPC after partial hydrolysis of DHA-PC mediated by phospholipase Aj. Conditions the same as in Figure 20.2 except that SC-COj pressure varied. 

Aquatic HS inhibited the base-catalyzed hydrolysis of the n-octyl ester of 2,4-D (i.e., 2,4-DOE). The hydrolysis rate of 2,4-DOE at pH 9-10 decreased by a factor equal to the fraction of the ester associated with the DHS. These observations are consistent with an unreactive humic-bound 2,4-DOE in equilibrium with reactive aqueous-phase 2,4-DOE. Thus, association between Dha and 2,4-DOE inhibited the base-catalyzed hydrolysis reaction. 

The first reaction is p-elimination in cysteine, serine, phosphoserine, and threonine residues due to attack by hydroxide ion, leading to the formation of very reactive dehydroalanine (DHA). In a cystine residue, this results in rupturing of the disulfide bond and liberation of a sulfide ion and free sulfur (Figure 13.4). Nucleophilic additions of the s-amino group of the protein-bound lysine to the double bond of DHA residue causes crosslinking of the polypeptide chain. After hydrolysis, a mixture of L-lysino-L-alanine and L-lysino-D-alanine, with probably a small proportion of dl and dd isomers,... 

Figure 13.5 Formation of lysinoalanine nucleophilic additions of the e-amino group of the protein-bound lysine to the double bond of DHA residue (a) causes crosslinking of the polypeptide chain (b) lysinoalanine (c) is formed after hydrolysis.

Dihydroartemisinin (DHA) is the active metabolite of acetalic derivatives of artemisinin (artemether, artesunate). Oxidation by cytochrome P450 enzymes or/and hydrolysis provides DHA, which is itself poorly stable in vivo. Indeed, the corresponding oxonium ion, a precursor of inactive metabolites by ring opening or by glucuronidation, can easily be formed (Figure 4.15). 

An anionic 1,4-silyl migration from C to C was observed during the lithiation of 9,10-dihydroanthracene (DHA) derivatives (equation 140)349 - 353. Typically, treatment of DHA 212 (R=SiMe3) with butyllithium followed by hydrolysis gave only ds-9,10-bis(trimethylsilyl)-DHA 213 (R=SiMe3, E=H) stereospecifically. The crossover and deuterium labeling experiments confirmed the intramolecular and irreversible feature of the... 

Many students have received degrees in recent years for exploring enrichment of marine oils (or other oils) by selective hydrolysis of triacylglycerols, or ester interchanges between esters and natural oils by enzymes. These explorations tend to be somewhat theoretical (100), but they can be effective, although impractical, for example, a 100-hour reaction time (101). Having a starting material rich in the desired product fatty acid (DHA) helped in one case (102), but the complexity of these proposed processes requires a separate article. 

The DHA dimer is converted to the monomer when it is dissolved in water. The chemistry of DHA is reviewed, including the hydrolysis to diketogulonic acid and the reactions of the 2- and 3-oxo groups. DHA readily forms Schiff bases and undergoes a Strecker reaction with amino acids. 

In the first place the discovery of the secretion of DHA-sulfate by the adrenal cortex in apparently major quantities suggested a hitherto completely unsuspected role of steroid sulfates in steroid biosynthesis and metabolism. Second, a number of steroid metabolites conjugated with two molecules of glucuronic or sulfuric acid were discovered, particularly in pregnancy urine, amniotic fluid, and in perfused placentofetal preparations. Finally, isotopic studies revealed several cases in which administered doubly labeled steroid conjugates were metabolized in the steroid part of the molecule without hydrolysis of the conjugate (e.g., D4, R5 cf. B5). 

The important 3y8-hydroxy-A steroids in umbilical cord blood and infant urine are also mainly present as sulfates (E2, E4, Ml, R6, S20) only very small portions of DHA and 16 -OH-DHA, for instance, have been found free in blood (S21). Because of the importance of sulfate conjugation, special care must be taken, if enzyme hydrolysis is used alone, to ensure the presence of the specific sulfatases required. For instance, at least one steroid present in infant urine is diconjugated and cannot be completely hydrolyzed by the enzymes in the crop fluid of... 

Figure 5. Possible processes for the synthesis of DHA and DPA concentrates from fish oils (modified after Haraldsson and Hjaltason, 2001). (1), Pseudomonas fluorescens lipase hydrolysis of tuna oil, resulting in 80% DHA+EPA in free fatty acids (Rakshit et al, 2000). (2), Rhizomucor miehei lipase ethanolysis of free fatty acids of tuna oil, resulting in 74% DHA + 3% EPA in free fatty acids (Haraldsson and Kristinsson, 1998). (3), Pseudomonas sp. lipase ethanolysis of fish oil, resulting in 50% EPA+DHA in acylglycerols (Haraldsson et al., 1997). (4), Two-step process Pseudomonas sp. lipase ethanolysis, resulting in 46% EPA+DHA in acylglycerols followed by urea fractionation, resulting in 85% EPA+DHA (Breivik era/., 1997). (5), Novozymes 435 lipase esterification of PUFA from cod liver oil with glycerol, resulting in >70% EPA+DHA in triacylglycerols (Esteban Cerdan et al., 1998).

More recent applications of the Sonogashira reaction in PUFA synthesis include Spurs and Rodriguez s synthesis of maresin 1 (56) [72], a potent anti-inflammatory lipid mediator derived from DHA (7). As shown in Scheme 3.21, the Sonogashira cross coupling reaction of alkyne 82, bearing an unprotected secondary alcohol, with vinyl iodide 83, provided compound 84. Then, removal of the TES group, Boland reduction of the triple bond, and subsequent hydrolysis of the methyl ester afforded maresin 1 (56). 

The rate of hydrolysis depends strongly on the nature of all three building blocks, i.e. the leaving group, the coordinated arene, and the chelate, and can be varied over several orders of magnitude, opening a time-window of activation. A detailed study of the aquation and the reverse, anation reactions of three [Ru(rj6-arene)Cl(en)](PF6) complexes (arene — bip (10), dha (11), and tha (12)) showed that the rates of aquation... 

As free DHAs are highly unstable compounds that readily undergo hydrolysis, they have generally been synthesized as their A-acyl derivatives or carboxylic esters and amides. For this reason DHAs occur in nature primarily as A-acyl derivatives or as part of a peptide sequence. Free DHAs 2 (Scheme 1) have not been characterized most probably they exist as imines 1 and consequently they readily undergo hydrolysis to give the corresponding a-oxo acid 3 and ammonia. 

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