Steroidal amides

Steroidal amides. Herz and Mantecon have prepared amides of lithocholic acid 3-formate in satisfactory yields by the EEDQ method. 

Steroidal amides. Herz and Mantccon- have prepared amides from lithocholic acid 3-foimate in sati.sfactory yields by the triphenyl phosphite method of Mitin and Glinskaya (3,322 323). 

Figure 16 Synthesis of a knot from a steroid-amide conjugate, showing the crystal structure of the product.

As a catalyst for ester and amide formation from acyl chlorides or anhydrides, 4-(di-methylamino)pyridine has been recommended (DMAP G. Hdfle, 1978). In the presence of this agent highly hindered hydroxyl groups, e.g. of steroids and carbohydrates, are acylated under mild conditions, which is difficult to achieve with other catalysts. 

Carbonylation of enol triflates derived from ketones and aldehydes affords Q,/)-unsaturated esters[332]. Steroidal esters are produced via their aryl and enol triflates[328]. The enol triflate in 477 is more reactive than the aryl tritlate and the carbonylation proceeds stepwise. First, carbonylation of the enol triflate affords the amide 478 and then the ester 479 is obtained in DMSO using dppp[333]. 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

A significant fraction of the body s cholesterol is used to form bile acids Oxidation m the liver removes a portion of the CsHi7 side chain and additional hydroxyl groups are intro duced at various positions on the steroid nucleus Cholic acid is the most abundant of the bile acids In the form of certain amide derivatives called bile salts, of which sodium tau rocholate is one example bile acids act as emulsifying agents to aid the digestion of fats... 

Lithium acetyhde also can be prepared directly in hquid ammonia from lithium metal or lithium amide and acetylene (134). In this form, the compound has been used in the preparation of -carotene and vitamin A (135), ethchlorvynol (136), and (7j--3-hexen-l-ol (leaf alcohol) (137). More recent synthetic processes involve preparing the lithium acetyhde in situ. Thus lithium diisopropylamide, prepared from //-butyUithium and the amine in THF at 0°C, is added to an acetylene-saturated solution of a ketosteroid to directly produce an ethynylated steroid (138). 

An isolated acetoxyl function would be expected to be converted into the alkoxide of the corresponding steroidal alcohol in the course of a metal-ammonia reduction. Curiously, this conversion is not complete, even in the presence of excess metal. When a completely deacetylated product is desired, the crude reduction product is commonly hydrolyzed with alkali. This incomplete reduction of an acetoxyl function does not appear to interfere with a desired reduction elsewhere in a molecule, but the amount of metal to be consumed by the ester must be known in order to calculate the quantity of reducing agent to be used. In several cases, an isolated acetoxyl group appears to consume approximately 2 g-atoms of lithium, even though a portion of the acetate remains unreduced. Presumably, the unchanged acetate escapes reduction because of precipitation of the steroid from solution or because of conversion of the acetate function to its lithium enolate by lithium amide. 

Apparently a substantial spacer is also allowable between I he aromatic ring and the carboxy group. Gemfibrozi 1 (52), a iiypotriglyceridemic agent which decreases the influx of steroid into the liver, is a cl ofibrate homologue. It is made readily liy lithium di isopropyl amide-promoted alkylation of sodium iso-propionate with alkyl bromide 51. 

The scheme used to prepare the direct 8-aza-analogue 21 of estrone bears at least formal similarity to the Torgov-Smith steroid total synthesis sequence. Acylation of the phenethylamine 9 with acryloyl chloride gives amide 16. Michael addition of dimethylamine followed by Bischler-Napieralski cyclodehydration gives the dihydroisoquinoline, 17. 

An asymmetric C-H insertion using a chiral 3,3, 5,5 -tetrabromosubstituted (salen)manganese(m) complex 107 with TsN=IPh afforded insertion products with ee up to 89%.258 Che reported the first amidation of steroids such as cholesteryl acetate with (salen)ruthenium(n) complexes 108.259... 

F. A. Omar, Cyclic Amide Derivatives as Potential Prodrugs. Synthesis and Evaluation of V-Hydroxymethylphthalimide Esters of Some Non-Steroidal Anti-Inflammatory Car-boxy he Acid Drugs , Eur. J. Med. Chem. 1998, 33, 123-131. 

Classical organic chemistry provides a wide variety of potential analytes for electron ionization, the only limitation being that the analyte should be accessible to evaporation or sublimation without significant thermal decomposition. These requirements are usually met by saturated and unsaturated aliphatic and aromatic hydrocarbons and their derivatives such as halides, ethers, acids, esters, amines, amides etc. Heterocycles generally yield useful El spectra, and flavones, steroids, terpenes and comparable compounds can successfully be analyzed by El, too. Therefore, El represents the standard method for such kind of samples. 

More recent developments in the field of the Pirkle-type CSPs are the mixed r-donor/ r-acceptor phases such as the Whelk-Of and the Whelk-02 phases.The Whelk-Of is useful for the separation of underiva-tized enantiomers from a number of families, including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, alcohols and non-steroidal anti-inflammatory drugs.It has been used for the separation of warfarin, aryl-amides,aryl-epoxides and aryl-sulphoxides. The phase has broader applicability than the original Pirkle phases. The broad versatility observed on this phase compares with the polysaccharide-derived CSPs... 

Phase II reactions (conjugate formation). Type II reactions couple their substrates (bilirubin, steroid hormones, drugs, and products of phase I reactions) via ester or amide bonds to highly polar negatively charged molecules. The enzymes involved are transferases, and their products are known as conjugates. 

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