Steroid-21-oates

Like in Chapt. 7, we begin the discussion with acetates, since acetic acid is the simplest nontoxic acyl group, formic acid being less innocuous. An informative study was carried out to compare the kinetics of hydrolysis of two types of corticosteroid esters, namely methyl steroid-21-oates (which are active per se) and acetyl steroid-21-ols (which are prodrugs), as exemplified by methyl prednisolonate (8.69) and prednisolone-21-acetate (8.70), respectively [89]. In the presence of rat liver microsomes, the rate of hydrolytic inactivation of methyl steroid-21-oates was much slower than the rate of hydrolytic activation of acetyl steroid-21-ols. Thus, while the Km values were ca. 0.1 -0.3 mM for all substrates, the acetic acid ester prodrugs and the methyl ester drugs had Vmax values of ca. 20 and 0.15 nmol min-1 mg-1, respectively. It can be postulated that the observed rates of hydrolysis were determined by the acyl moiety, in other words by the liberation of the carboxylic acid from the acyl-enzyme intermediate (see Chapt. 3). 

D. Kumari, H. J. Lee, Hydrolysis of Methyl Steroid-21-oates and Acetyl Steroid-21-ols by Rat Liver Microsomes , Drug Metab. Dispos. 1985, 13, 627-629. 

OATs) non-steroidal anti-inflammatory drugs, antiviral nucleoside analogues... 

Within the OAT family, OAT4 is the only transporter expressed at appreciable levels in both the placenta and in the kidney [54]. The membrane localization of OAT4 within these tissues has not been examined. Steroid sulfates, and ochratoxinA are efficient transport substrates of OAT4, whereas PAH is weakly transported [54]. The functional importance of OAT4 in regulating placental permeability and renal drug elimination is currently unknown. 

Isomerization of the diterpeue A B ring juncture. The steroidal type A/B ring juncture of diterpenes can be isomerized to the antipodal one by treatment with a 10% palladium-charcoal catalyst in refluxing triglyme. Thus methyl 5a,10 -podocarpa-8,1 l,13-triene-15-oale (1) can be isomerized in 83% yield to methyl 5j, IOa-podocarpa-8,ll,13-triene-l3-oate (2). The reaction was used in a synthesis of (- J-podocarpic acid from (+)-dehydroabietic acid. 

Studies aimed at the synthesis of the tetracyclic steroid skeleton from dehydro-abietic acid have centred, in their initial stages, on transformations of the C-13 isopropyl group. The full paper describing the conversion of methyl 12-acetyl-abieta-8,ll,13-trien-18-oate into methyl 13-hydroxypodocarpa-8,ll,13-trien-18-oate by nitrodeacylation and dealkylation reactions, has appeared. Birch reduction of the methyl ether of the phenol afforded the a/5-unsaturated ketone (56) which is a useful synthetic intermediate. Methods for the conversion of podocarpic acid into the a) -unsaturated ketones (57 R = CO2H and CHjOAc) have been investigated reduction of the ester (58 R = C02Me) with lithium in liquid ammonia, which was accompanied by decarboxylation, gave only a... 

In rats, OAT-K2, as OAT-Kl, was localized in the apical membrane of straight proximal tubule [52]. When transfected in cultured epithehal cells, it mediates not only the apical transport of methotrexate and folate but also that of taurocholate and prostaglandin E2. In cis-inhibition studies, steroids, bile acid analogs, and cardiac glycosides were shown to have a high affinity for OAT-K2, suggesting that it participates to the apical transport of hydrophobic anionic compounds in the kidney [52]. 

The OAT proteins play a critical role in the excretion and detoxification of a wide variety of drugs, toxins, hormones and neurotransmitter metabolites. A number of common non-steroid anti-inflammatory drugs (NSAID), including acetyl salicylate and salicylate, acetaminophen, diclofenac, ibuprofen, ketoprofen, indomethacin, and naproxen, are substrates of one or more OAT isoforms, so that there can be significant interactions between NSAlDs and other drugs. The 3-lactam antibiotics (penicillins, cephalosporins and penems) and the antiviral nucleosides adefovir, cidofovir,... 

In the C -C bond formation of more complex cyclic systems, such as the steroid derivative ethyl 3/J-(/tTt-butyldimethylsiIyloxy)-20-phenylseleno-5-pregnen-21-oate, 1.2-induction is also effective 10. Reaction with tributyl(2-propenyl)stannane yields the diastcrcomeric steroids in a ratio of 90 10. 

More complex cyclic systems, such as steroids, also react with high 1,2-stereoinduction. The radical reduction of ethyl 3/ -(/er/-butyldimethylsilyloxy)-20-phenylseleno-5-prcgnen-21-oate shows a diastereoselectivity of 7 1 [(20/ )/ (20S)]23. 

Maitra. U. Bag. B.G. Rao. P. Powell. D. Bile acids in asymmetric synthesis. 5. Asymmetric synthesis of steroidal Troger s base analogs. X-ray molecular structure of methyl 3a, 12a- 6H, 12H-5.1 I -methanodibenzo[b,f][l,5]diazo-cine-2,8-bisacetoxy -5P-cholan-24-oate. J. Chem. Soc., Perkin Trans. 1 1995, 2049-2507. 

Note that the investigation of the details of the degradation pathway of C-, D-rings of 9,17-dioxo-l,2,3,4,10,19-hexanorandrostan-5-oate and other side chains of steroid compounds (E-, F-rings of diosgenin) are still in progress [18]. 

A similar structure is seen in steroid bisdesmosides of oats Avena sativa, Poaceae), which are called avenacosides (10-70). Specific P-glucosidase present in oat leaves hydrolyses avenacosides (spHts-off glucose bound at C-26) to monodesmosides called deglucoave-nacosides, which are less bitter, but exhibit higher antimicrobial and haemolytic effects. 

Linker, M. and Kreiser, W. (2002) Synthesis of (20R)- and (20S)-epimers of methyl 3-oxochola-l,4, 22-trien-24-oate, a steroid from the octocoral Dendronephthya sp. Hdv. Chim. Acta, 85,1096-1101. 

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