Steroidal amines

The diphenylmaleimide is prepared from the anhydride, 33-87 % yield, and cleaved by hydrazinolysis, 65-75% yield. It is stable to acid (HBr, AcOH, 48 h) and to mercuric cyanide. It is colored and easily located during chromatography, and has been prepared to protect steroidal amines and amino sugars. " ... 

The reduction of oxime derivatives (section IV-C) is useful for the preparation of steroidal amines labeled with a deuterium on the nitrogen-bearing carbon atom... 

The reactions are generally run at room temperature or below. With steroids the product is usually isolated by addition of the reaction mixture to water followed by filtration or extraction. The inorganic product of the reaction, chromium III, is soluble in neutral or aqueous acid solutions and can be removed by washing. When steroidal amines are oxidized, the work-up is usually modified such that the steroid may be extracted from the insoluble basic chromium III salts. °... 

Conclusive evidence for INCs was first presented by Longevialle and Hotter [175,176] who demonstrated the transfer of a proton from an imine fragment to an amino group located on the opposite side of the rigid skeleton of bifunctional steroidal amines. [176] Such a proton transfer cannot proceed without the intermediacy of an INC otherwise, a conventional hydrogen shift would have bridged the distance of about 10 m between the respective groups which is about five times too far. 

SBSE can be successfully used in the analysis of environmental samples [93-97] and for food analysis [98, 99]. PDMS is the most commonly used polymer, primarily because of its thermal stability and durability. SBSE has been modified by application of derivatization with different reagents (acetic anhydride, BSTFA, etc) [100-104]. This approach is suitable for the extraction of compounds requiring derivatization. The use of multistep derivatization with several extraction elements (each reaction is performed on a different stir bar) allows efficient extraction, desorption, and chromatographic analysis of compounds with different functional groups (e.g., phenols, steroids, amines, thiazoles, ketones). Acetic anhydride (ester formation), ethyl chloroformate (reaction of acids and amines), tetraethyloborane, and sodium bis-trimethylotrifluoroacetamide have been used for extraction and simultaneous derivatization [105]. 

Z 57 have employed gas-liquid chromatographic analysis of products, and have given results (marked - in Table 26) in significant contrast to earlier data for the same amines [6]. The other results listed in Table 26 must therefore be treated with caution until they have been confirmed or revised by the application of modern analytical methods. Nevertheless certain conclusions can be stated, with confidence at least in their qualitative validity. The most obvious is the preponderance of elimination over substitution in the reactions of axial amines. It is also clear, with the above reservation concerning product analyses, that the hydroxylic products are formed with predominant retention of configuration, although early reports of total retention in the substitution of equatorial steroid amines have been corrected for C(3) amines [4,5] and seem likely to be varied in other cases. 

We are now in a position to interpret the reactions of steroid amines, particularly with respect to the dominant retention of configuration in substitution and the considerable or exclusive elimination of axial amino groups. Shoppee has pointed out [3] that the ratio, elimination/substitution, for a series of axial amines follows the order expected on the basis of steric hindrance to the formation of the axial alcohol. In simple mono- and bi-cyclic systems, as well as in acycUc amines, the proportion of olefinic products is far lower (often ca. 30% than for many steroids. This agrees with the concept that very high yields of olefins result from steric frustration of cis substitution. A semi-quantitative correlation of olefin yield with the number and nature of the sy -diaxial interactions at the reaction centre is even possible (Table 27). 

PRODUCTS FROM REACTIONS OF STEROID AMINES WITH NITROUS ACID... 

Recently, two new methods have been introduced for this transformation. In one, formic acid is replaced by sodium borohydridc. Thus treatment of a steroidal amine of type (I) with a large excess of formaldehyde in methanol followed by reduction with sodium borohydridc gives the methylated amine (2) in about 85% yield. 

Circular Dichroism. The salicylidene-imino chirality rule has been applied to cyclic steroidal amines. This rule was previously used to correlate the absolute configuration of cyclic terpenoid amines with the signs of the observed Cotton effects near 255 and 315 nm in their circular dichroism spectra. Similar considerations were used to interpret the c.d. spectra of fV-salicylidene derivatives of steroidal cyclic amines. These spectra were reported but no simple interpretation was possible. 

Syntheses and antimicrobial activity of some steroidal amines in the 1,3,5(10)-oestratriene series, (125) and (126), have been reported. ... 

Steroid amines to nitrosteroids. This peracid is the preferred reagent for oxidation of 3a-aeetoxy-20a-amino-5 8-pregnane (I) to 3a-acetoxy-20a-nitro-5 8-pregnane (2). The amine was added slowly to a solution of 7 equivalents of the peracid in... 

Since the establishment of the structure of conessine (1), and the discovery of numerous steroidal amines, the theoretical and economic interest of the steroidal amines and alkaloids has stimulated very active chemical research on the plants of the Apocynaceae and Buxaceae families. The main points in this work are set out in two monographs. The present account is confined to the results obtained since 1966 and deals only with the Apocynaceae and Buxaceae families. The Solanaceae and Veratrum groups are not included. 

Leaves of the various Holarrhena species contain steroidal amines characteristic of the species. Thus, methylholaphylline (10), holaphyllinol (11), holaphylli-dine (12), and dihydroholaphyllamine (3)S-amino-20-oxo-5a-pregnane) are found in the leaves of H. floribundaP... 

The steroidal amines and alkaloids are starting materials for the preparation of steroids used in therapy, and are excellent substrates for the study of many reactions. 

Steroidal amines with nitrogen at C-3 or C-20 can be converted into steroidal hormones." Beckmann rearrangement of the oxime (45) of funtumine gives 3a,17j3-diamino-5a-androstane (46). Ruschig deamination of the latter gives androstanedione In the same way, the alkaloids of H. floribunda,... 

The steroidal diamines, irehdiamine-A (244) (IDA) and malouetine (243) (MAL), exert an inhibiting action on the growth of bacteriophage T2 in infected cells of Escherichia coli. Bacteriophage-directed DNA synthesis is more sensitive to steroidal amine inhibition than RNA or protein synthesis, and it is proposed that DNA is the primary target of steroidal diamine action. 

The toxicity of steroidal amines is such that it is sometimes difficult to perform on them the microbiological reactions normally done with other steroids. How-... 

C. Mass and N.M.R. Spectra of Steroidal Amines.—A study has recently been made18 of the mass spectral fragmentation pattern of the dimer (28), obtained by reduction of the cyanamide of conanine with lithium aluminium hydride.19 As with certain benzylamines, a major fragment has been interpreted to arise from a heterolytic rupture of the C—N= bond. 

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