Deoxycholic acid, synthesis

The example given above of the selection of deoxycholic acid as a SM for the synthesis of cortisol also illustrates the use of a chiral natural substance as synthetic precursor of a chiral TGT. Here the matching process involves a mapping of individual stereocenters as well as rings, functional groups, etc. The synthesis of helminthosporal (105) from (-i-)-carvone (106)21 and the synthesis of picrotoxinin (107) from (-)-carvone (108)22 amply demonstrate this approach employing terpenes as chiral SM s. 

A key step in Kendall s synthesis of cortisone [126] from deoxycholic acid is the conversion of the iijff,i2a-dibrom0" compound (22) into the bromo-ketone 25) by aqueous chro-... 

Kendall s synthesis of cortisone from deoxycholic acid [26] included two interesting allylic reactions in ring C. The 3a,i2a dihydroxy -5jS-9(ii)-ene (36) was readily converted into the i2a-bromo (37) or i2a-chloro derivative by the action of the... 

More frequently encountered are acquired defects in bUe acid synthesis, which have been noted in Liver diseases such as hepatitis and cirrhosis. In acute hepatitis, alterations of bile acid synthesis and conjugation occur because of hepatic parenchymal cell disease. In cirrhosis, there is a marked reduction in cholic acid synthesis with a low concentration of biliary deoxycholic acid. These abnormalities are due both to decreased synthesis and to portosystemic shunting. The... 

Derivation Isolation from adrenal cortex extract, synthesis from deoxycholic acid. 

Synthesis of the bile acid (75) conjugated to either the 3 -end of an ODN or via a linker to the of dU are described. When used in vivo in rats, there was an increase in uptake to the liver, and this may be a method of targeting applications, such as antisense, to hepatic cells. The steroid 7-deoxycholic acid has also been incorporated into DNA via the of dU. When used in TFOs, there was an increase in the triplex stability compared to unmodified controls. 

Pregnanes. In 1944, Sarrett completed the first partial synthesis of cortisone (172). Like many of the eady syntheses of corticosteroids, Sarrett began with the a bile acid, deoxycholic acid (14). Because bile acids are isolated from animal sources, their supply is by necessity limited (173). Following these early syntheses, several improvements and innovations have resulted in a number of industrial syntheses of cortisol and other corticosteroids. 

The trogerophane based on the deoxycholic acid chiral template in 25 [and in its (/ ,/ )-epimer] was used for an asymmetric synthesis of the enantiopure Troger s base analogues after hydrolysis.As the two hydroxyl groups of deoxycholic acid have different reactivities for esterification, unsymmetric Troger s bases could be asymmetrically synthesized as well. 

The situation in the decompensated patients is less well understood. These patients, in the author s experience, have greater than 100 cm resection and often have an ileal transverse colostomy. The bile acid synthesis rate is quite similar to that in the compensated patients, but in an occasional patient it seems to be lower. The bile acids of bile contain a normal or high proportion of deoxycholic acid, and fecal bile acids are predominantly lithocholic acid and deoxycholic acid. Jejunal concentrations of bile acids are markedly reduced, and up to one-half of the bile acids which are present may have... 

The reason for the low bile acid formation in familial hypercholesterolemia is not known. It could be due to impaired availability of cholesterol to the pool which is utilized for bile acid synthesis, a partial deficiency or inhibition of the enzyme system producing bile acids, deficient hepatic secretion of bile acids, or augmented intestinal reabsorption. An interesting observation is that the bile of hypercholesterolemic patients may contain relatively little or no deoxycholic acid (23,73,157), a finding recorded also in patients... 

Studies with radioactive glycocholate or taurocholate demonstrated a virtual absence of the enterohepatic circulation of bile acids in patients with jejunotransversocolostomy (77). The small amount of absorbed bile acids contained some deconjugated cholate and deoxycholate (which had been reconjugated in the liver), indicating a rapid bacterial action during an apparently fast intestinal passage. Under these conditions, steatorrhea is apparently not solely due to bile salt deficiency induced impairment of micelle formation, but reduced absorptive area may play an important contributory role. No direct measurement of bile acid synthesis by fecal determination has been performed in this condition. 

Since, in the rat, cholesterol is eliminated largely in the form of bile acids, it was expected that bile acid secretion in bile would be increased in the hyperthyroid state. Early experiments to test this point indicated that biliary bile acid secretion was actually normal or below normal (2,3). These results can be explained in terms of the inadequate analytical procedures then in use. Only cholate secretion was measured, and the levels of cheno-deoxycholate were not taken into account. When both of these bile acids were determined, it was shown that, in the bile fistula rat, the total production of bile acids was about the same in the hyperthyroid as in the euthyroid state, and lower in the hypothyroid state (4). In addition, in the hyperthyroid state, the normal ratio of cholate/chenodeoxycholate was reversed from approximately 3 1 to 1 3—cholic acid synthesis was decreased, and chenodeoxycholic acid synthesis was increased two- to threefold (4). Identical results were obtained in the bile fistula rat treated with noncalorigenic doses of D-tri-iodothyronine (5,6), suggesting that these effects are not necessarily a function of the basal metabolic rate. 

The demonstration by Bergstrom et al. (4,5) in 1953 of the conversion of deoxycholic acid to taurocholic acid in the rat in vivo and by rat liver slices paved the way for studies on 7a-hydroxylation and conjugation of bile acids. The early work on the synthesis of bile acid conjugates in vitro utilized slices or homogenates of rat and human liver, and the enzymatic reaction was followed by the incorporation of radioactivity from carboxyl- C-labeled bile acids into the corresponding taurine and glycine conjugates (6,7). The... 

Since rheumatoid arthritis was (and is) a grave and crippling disease, with a h h Incidence, there was a tremendous incentive to provide cortisone by an efficient synthetic technique. Sarett, among others, had been working on the partial synthesis of adrenocorticoid hormones, and in 1946 he achieved the first synthesis of cortisone. The cortisone for the Hench-Kendall clinical experiment was prepared at Merck based on synthetic methods devised by Sarett and by KendaU and his co-workers. The starting material was deoxycholic acid, which was readily available from bovine... 

Deoxycholic acid, 3a,12a-dihydroxy-SP-cholan-24-oic acid a bile acid, M, 392.56, m.p. 176-177°C, [a]n + 55° (ethanol). D. is found in the bile of most mammals, including man, dog, ox, sheep and rabbit. It can be used as starting material for the partial synthesis of therapeutically important steroid hormones. 

We found that a natural steroidal acid, deoxycholic acid and its derivative, apocholic acid (Figure 1), can serve as effective host components for inclusion polymerization [1-4]. These hosts meet the requirements for the synthesis of stereoregular as well as optically... 

Deoxycholic acid was an important starting material for the early synthesis of cortisone and other cortical steroids. It was obtained principally from cholic acid by selective oxidation and subsequent Wolff-Kishner reduction. Cholic acid was obtained from beef bile which also contains substantial amounts of deoxycholic acid. The history of this period of steroid investigation is reviewed by Fieser and Fieser (1). 

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