Hydroxylation in the side chain

The origin of the 3a,7a,12a,23 -tetrahydroxy-5 -cholanic has been studied [163] with subcellular fractions of adder Vipera berua) liver with the following conclusions the active microsomal enzyme requires NADPH and O2 deoxycholate is not converted to cholate, but to 3a,7, 12a-trihydroxy-5)8-cholanate. Bitocholic acid could result from two pathways (a) cholate is converted to 3a,7a,12a,23 -tetrahy-droxy-5j8-cholanate by hepatic 23-hydroxylase the tetrahydroxy acid is 7a-dehy-droxylated by intestinal microorganisms to produce bitocholate (the 3a,12a,23 -tri- 

Products identified from incubation of [24- C]deoxycholate with a microsomal fraction of adder liver included 12a-hydroxy-3-oxo-5 8-cholanate, 3a,7j8,12a-trihy-droxy-5y8-cholanate and bitocholate, but no bitocholate was detected from similar incubations with [24- C]cholate [163]. 

23-Tetrahydroxy-5j8-cholanic acid has also been identified by mass spectrometry as a significant constituent of the taurine fraction from urine of cholestatic subjects [164]. Further comment will be found in Section VI.3. 

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Su ate esters. Baumgarten showed that the reagent sulfates substances such as hydrazine, diethylamine, phenol, and naphthalene. It has been used in preparation of carbohydrate sulfate esters, sterol sulfate esters, phenol sulfate esters. 2-Hydroxy-3-alkyl-l,4-naphthoquinone antimalarials can be separated from metabolites hydroxylated in the side chain by conversion of the hydroxylated metabolites into water-soluble sulfate esters and extraction with water. Hydroxy-hydrolapachol (1), which was identified as a metabolite of hydrolapachol and which... 

Substituting N, O, or S atoms at various places or saturating the double bond to produce hexahydrocannabinol probably retains activity. fSeeCA 74,125667(1971) for S analogs.] Alkoxy side chains at 5 retain activity. Unsaturated side chains arc as active as saturated ones. Ether moieties at the 5 position, but not as the 3, retain activity. Activity is retained if an additional alkyl is placed at 4 but lost if placed at 6. Activity is greatly decreased or lost if the H at the 4 or 6 positions is replaced by carboxyl, carbomethoxyl, acetyl or acetoxyl if the hydroxyl is replaced by H if the OH is at 5 and the side chain at 4. Methyl and/or ethyl at 1 and 5 retains activity, as does removal of the methyl at 1. An hydroxyl in the side chain is active, but not on... 

Patent filings from Taisho Pharmaceutical Co. had claimed already by 1990 a new and promising approach towards calcitriol via microbial (lS,25)-dihydrox-ylation of cholecalciferol. [105, 106] Nocardia autotrophica hydroxylates both positions, whereas Amycolata autotrophica, in contrast, shows a preference for mono-hydroxylation in the side-chain. 

Triterpenoids (C30 compounds) are the most ubiquitous of the terpenoids and are found in both terrestrial and marine flora and fauna (Mahato et al., 1992). Diterpenoids and triterpenoids rarely occur together in the same tissue. In higher plants, triterpenoid resins are found in numerous genera of broad-leaved trees, predominantly but not exclusively tropical (Mills and White, 1994 105). They show considerable diversity in the carbon skeleton (both tetracyclic and pentacyclic structures are found) which occur in nature either in the free state or as glycosides, although many have either a keto or a hydroxyl group at C-3, with possible further functional groups and/or double bonds in the side-chains. 

A particular mechanism of barbiturate ring opening has been observed for some barbiturates hydroxylated on the side-chain. The mechanism and relevance of this tautomeric lactam-lactone equilibrium are discussed in Chapt. 11. 

CASRN 314-40-9 molecular formula C9Hi3BrN202 FW 261.12 Soil Metabolites tentatively identified in soil were 5-bromo-3-(3-hydroxy-l-methylpropyl)-6-methyluracil, 5-bromo-3-5ec-butyl-6-hydroxymethyluracil, 5-bromo-3-(2-hydroxy-l-methylprop-yl)-6-methyluracil, and carbon dioxide. The presence of uracil products suggests that bromacil was degraded via hydroxylation of the side chain alkyl groups. In the laboratory, 25.3% of C-bromacil degraded in soil to carbon dioxide after 9 wk but mineralization in the field was not observed. The half-life of bromacil in a silt loam was 5-6 months (Gardiner et al, 1969). 

Structural features such as electrical charge, hydroxyl groups in the side-chains and amino atoms of the amide groups reduce the lipophilicity (increase the hydrophilicity) whereas additional methyl groups sitting on amino moieties or free positions on the benzene ring increase the fipophilicity. Biliary contrast agents with a free position have > 5. 

Sterols are steroid alcohols. They have a P-positioned hydroxyl group at C-3 and one or more double bonds in ring B and in the side chain. There are no further oxygen functions, as in the carbonyl and carboxyl groups. 

Fig. 5. Influence of substituents at the catecholamine molecule the hydroxyl-groups at the phenyl-ring are mendantory for any affinity to all adrenoceptor subtypes. The substituent at the nitrogen in the side chain determines the degree of affinity...

For all indications without an involvement of the heart the /3i-effects are unwanted. Therefore efforts have been made to develop selective /32-sympatho-mimetic. By further increasing the size of the substituent at the N-position in the side-chain (beyond isopropyl) and altering the position of the hydroxyl-moieties at the phenylring, compounds emerge with a much higher affinity towards P2- than... 

Franssen et al. [24] pointed out an alternative method of production of nootkatone from valencene catalysed by (-i-)-germacrene A hydroxylase, an enzyme of the cytochrome P450 monooxygenase type that was isolated from chicory roots. In general, this enzyme appeared to accept a broad range of sesquiterpenes and hydroxylates exclusively at the side-chain s isopropenyl group. Valencene is an exception it was not hydroxylated at the side chain, but -nootkatol was formed in the first step (Scheme 22.5) it is not yet clear if the second step is enzyme-catalysed. 

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