Oxo-DHA

In Pinaceae resins, for instance, fully trimethylsilylated derivatives of 7-hydroxy-DHA, 15-hydroxy-DHA and 15-hydroxy-7-oxo-DHA have been identified, as well as all the other abietadiene and pimaranediene acids present in these resins. The derivatization was ineffective on some labdane alcohols such as larixyl acetate, a marker compound for Venice turpentine, but in general labdane compounds have been identified in their trimethylsilylated form. Labdane acids, such as communic, agathic, agathalic, agatholic and acetoxy agatholic acids, that are among the most important constituents of sandarac... 

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. 

If benzyl carbamate is used as the amide component in the reaction with a-oxo acids 23 then the Na-benzyloxycarbonyl-DHA 24 is obtained directly (Scheme 8). Shin and et al.[77 84l widely exploited the above method in the synthesis of various a, 3-didehydropeptides (Table 3). In presence of 3 M thionyl chloride and acetyl chloride, 24 gave the A-carboxy-DHA anhydride ANCA 25, which could be conveniently converted into dehydropeptides.[77 84 Compared with the common saturated A-carboxy-a-amino acid anhydrides (NCAs), ANCAs were found to be stable at room temperature for several months. 

The reaction of a-oxo acids with nitriles in the presence of an add catalyst gives acylamino acrylic acid derivatives, which are then used to prepare a.P-didehydropeptidesJ85 861 The reaction proceeds with a high degree of purity and is less time consuming. The reaction takes place initially to give the imino chloride 26, which subsequently reacts with the enolic form of the oxo acid. Several a-haloacyl-DHAs 27 have been prepared (Scheme 9) from which the corresponding a-aminoacyl-DHA can be prepared by ammonolysis in aqueous ammonia. 

As discussed in Section 11.1.1.2.3 most of the aliphatic DHAs such as AAla, AVal, ALeu, Alle, AAsp, AGlu, and AOrn have been prepared either by (3-elimination, N-chlorination/ dehydrochlorination, or from Af-carboxy a, 3-didehydroamino acid anhydrides which, in turn, are prepared by condensation of an a-oxo acid with benzyl carbamate. 

SYNS 2-ACETYL-5-HYDROXY-3-OXO-4-HEXENOIC ACID A-LACTONE 3-ACETYL-6-METHYL-2.4-PYRANDIONE 3-ACETYL-6-METHYLPYRANDIONE-2,4 3-ACETYL-6-METHYL-2H-PYRAN-2,4(3H)-DIONE DEHYDRACETIC ACID DEHYDROACETIC ACID (FCC) DHA DHS... 

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. 

Following the approach taken by Eisner and Kuthan in their review of dihydropyridines,1 this article will incorporate only isolable or spectroscopically identified monocyclic dihydrodiazines and dihydrotriazines. We specifically exclude compounds containing exocyclic double bonds, i.e., particularly azine methenes, as well as oxo-, thio- or iminodihydroazines (5a), which can be considered as tautomeric azines (5b), and hydroxy, mercapto, and amino DHA (6a), which can exist in the tautomeric tetrahydroazine form (6b). 

Fig. 2. A typical 20 X 20 cm thia-layer chromatography plate for the assay of the following compounds in infant urine A, pregnenolone B, DHA C, unknown D, 21-OH-pregnenolone E, androstenediol F, 16-oxo-androstenediol G, 16a-OH-DHA H, 16,8-OH-DHA I, 16a-OH-pregnenolone. The position of androstenetriol (not assayed) is shown at J. Samples of 16a-OH-DHA were run in positions 1 (1J25 gg), B (3.75 /xg), and 7 (5.0 /xg). Samples (2A jig) of all the steroids measured (except for the unknown and 16/8-OH-DHA) were run in position S. Duplicate extracts of urines collected from the same baby on days 1, 2, 3, 4, 5, and 6 of life were run in positions 4, 6, 8, 9, and 10. The plate was sprayed with antimony trichloride then heated. From Shackleton and Mitchell (S9).

Fig. 3. Part of a 20 X 20 cm thin-layer chromatography plate for the assay in urine of A, androsterone B, DHA C, etiocholanolone D, 11-oxo-androsterone E, 11-oxo-etiooholanolone F, llj8-OH-androsterone G, llj8-OH-etiocholanolone. Standard compounds have been run in positions 1, S, 6, and 8. Duplicate extracts from normal adult urines have been run in positions 2, 4, and 5 from a normal day-old infant in position 7 and from an infant with the adrenogenital syndrome in position...

Evidence that the A steroids are of adrenal origin has been supplied by Reynolds (R2), who showed that the urinary excretions of 16a-OH-DHA and 16-oxo-androstenediol were 0.3-1.4 mg/24 hours in a newborn female with the C-21 hydroxylase deficiency type of congenital adrenal hyperplasia. These fell to undetectable amounts with dexamethasone suppression therapy. A very low excretion of three 3y8-hydroxy-A steroids was found by the authors in the case of a baby shown subsequently at autopsy to have little adrenal tissue (see Section 11). Further circumstantial evidence is given when abnormalities are considered in Section 11 and also the effect of corticotropin in Section 12. 

Of the compounds measured, androstenediol, 16-oxo-androstenediol, 16a-OH-DHA, and androstenetriol may be considered to be estrogen precursors (or the metabolites of estrogen precursors) produced initially by the fetus for aromatization in the placenta. 16a-OH-pregnenolone is not an immediate precursor of estrogen but is possibly simply a catabolic product of the quantitatively very important steroid, pregnenolone (Section 4.2.1). 

The recent identification of 16y8-OH-DHA as a major compound in infant urine (S13, Tables 13 and 14) plus the fact that under certain conditions it spontaneously isomerizes to the more stable 16-oxo-andros-tenediol, raises the question to what extent 16-oxo-androstenediol, also reported as a major component in infant urine (R2, S9, Tables 13 and... 

The first indication of possible adrenal hypoplasia in an infant studied by the authors was the finding of an abnormally low level of estriol in plasma obtained from the mother prior to delivery. The urinary excretion of 16a-OH-DHA, 16-oxo-androstenediol, and 16a-OH-pregnenolone was only about one-tenth that expected for normal newborn infants. This infant died of respiratory failure 30 hours after birth postmortem examination showed very small adrenal glands. 

Dehydroacetic Acid. 3-A cctyl-b-melhyl 2H-py-ran-2,4(3H)-dione 2-acetyl-5-hydroxy-3-oxo-4-hexenoic acid i-lactone methylacetopyronone DHA. CjHjO mol wt 168.]4. C 57.14%, H 4.80%, O 38.06%. Polymerization product of ketene Steele er al. J. Org. Chem. 14, 460 0949)- From ethyl acetoacetate Arndt, Org. Syn. coll, vol. Ill, 231 (1955). Series of articles on toxicity studies, pharmacology, mechanism of action, absorption, distribution, renal action J. Pharmacol. Exp Ther. 99, 57-111 (1950). 

Synonyms 3-Acetyl-5-hydroxy-3-oxo-4-hexenoic acid A-lactone 3-Acetyl-6-methyl-1,2-pyran-2,4(3H)-dione 3-Acetyl-6-methyl-2,4-pyrandione 3-Acetyl-6-methylpyrandione-2,4 3-Acetyl-6-methyl-2H-pyran-2,4(3H)-dione Dehydracetic acid DHA DHS Methylacetopyronone... 

Synonyms Dehydroacetic acid sodium salt DHA-Na 4-Hexenoic acid, 2-acetyl-5-hydroxy-3-OXO-, A-lactone, sodium deriv. 3-(1-Hydroxyethylidene)-6-methyl-2H-pyran-2,4(3H)-dione sodium salt 2H-Pyran-2,4(3H)-dione, 3-acetyl-6-methyl-, monosodium salt Sodium dehydroacetic acid Sodium dehydroxyacetate Sodium 1-(3,4-dihydro-6-methyl-2,4-dioxo-2H-pyran-3-ylidene) ethanolate... 

Experimental work by the group of Arnold proves that it is possible to functionalize the 0X0 group of uranyl in a macrocyclic environment with a silane SiMea or make a C-H activation of dihydroanthracene (DHA), even though it is well known that the interaction between uranium and oxygen is very strong and leads to a chemically inert oxo group (Figure 13.7). 

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