Androstane, structure

Most AAS androstane structures possess an adrenalgenic stimulatory effect. The magnitude of this effect is decided by the level of androgenic value the drug maintains. For anyone who has had to stand in a DMV or Post Office line while administering Halotestin, this is stating the obvious. 

The members of this group listed in Table 31, all have a keto-group in position 3, a double bond between C atoms 4 and 5, and an OH group at the 17 position, although this is esterified in some cases. Testosterone, methyltestosterone, fluoxymesterone and methandienone are all based on the androstane structure, having methyl groups in both the 10 and 13 positions and norethandrolone and nandrolone have a methyl group at C 13 only. In addition, methandienone has a second double bond in the... 

B-Homosteroids were first reported by Ringold in the course of an investigation of the relationship of structural changes to biological activity of anabolic agents. The Tiffeneau rearrangement sequence described earlier for the preparation of A-homosteroids was used to synthesize 17/ -hydroxy-B-homo-5a-androstan-3-one (56a). 

The many hormone analogs prepared in the 10(54)uZ)eo-estr-4(10)-ene-3,5-dione and the 10(54i H)uZ)eo-androstane-3,5-dione series clearly demonstrates that a wide range of functional groups may be safely carried through these synthetic sequences or that the resulting products have the requisite functionality for further structural elaboration. 

Kurath described the conversion of 3a,17y5-diacetoxy-5)9-androstan-12-one (partial structure 78) to diketone (79) by bromination of (78) and hydrolysis of the C-11 epimeric bromo ketones... 

The 1,11 -etheno-derivative (8) of oestrone methyl ether has an unusually flat structure, as a consequence of the presence of the extra aromatic ring." X-Ray analysis has established the geometry of 3a, 17a-dihydroxy-4,4,14a-trimethyl-19-nor-10a-pregn-5-ene-l 1,20-dione (9)" and the configuration of the S=0 bond in 2a,3a-epithio-5a-androstan-17/3-ol (R) S-oxide (10)."... 

The signal assignments of the parent compounds 5 a- and 5 /i-androstane, 5 a- and 5 /i-pregnane and estrane [564] were performed by comparing the spectra with closely related derivatives, using substituent effects, off-resonance decoupled spectra and specifically deuterium-labeled analogues [564], The influence of different structural environments on the 13C chemical shift of the carbonyl carbon in keto steroids is illustrated by the values given in Table 5.10 [566]. The carbonyl carbon atom frequency in cyclopen-tanone moieties is shifted about 5 ppm downfield relative to that in cyclohexanone... 

Compendial reviews state that rocuronium bromide had been identified as having eight different impurities, which are labeled as impurities A, B, C, D, E, F, G, and H. Impurity A (i.e., related compound A) is 3a-hydroxy-2/i (morpholin-4-yl)-16/ -(pyrrolidin-l-yl)-5a-androstan-17/ -yl acetate impurity B (i.e., related compound B) is l-[3a,17/i-bis(acetyloxy)-2/i-(morpholin-4-yl)-5a-androstan-16/i-yl]-l-(prop-2-enyl)pyrrolidinium impurity C (i.e., related compound C) is l-[3a,17/i-dihydroxy-2/i-(morpholin-4-yl)-5a-androstan-16/ -yl]-l-(prop-2-enyl)pyrrolidinium and impurity D (i.e., related compound D) is l-[3a-(acetoxy)-17/J-hydroxy-2/J-(morpholin-4-yl)-5x-androstan-16/j-yl]-l-(prop-2-enyl)pyrrolidinium impurity E (i.e., related compound E) is l-[17/ -(acetoxy)-3a-hydroxy-2/ -(pyrrolidin-l-yl)-5a-androstan-16/)-yl]-l-(prop-2-enyl)pyrrolidinium impurity F (i.e., related compound F) is l-[3a,17/ -bis(acetiloxy)-2/ -(pyrrolidin-l-yl)-5a-androstan-16/i-yl]-l-(prop-2-enyl)pyrrolidinium impurity G (i.e., related compound G) is 2/)-(morpholin-4-yl)-16/i-(pyrrolidin-l-yl)-5a-androstane-3a,17/i-diol and impurity H (i.e., related compound H) is l-[17/i-(acetyloxy)-2-(morpho-lin-4-yl)-3-oxo-57-androst-l-en-16/i-yl]-l-(prop-2-enyl)pyrrolidinium [5-7], The molecular structure of rocuronium bromide is shown in Fig. 6.1, while the structures of the known impurities are illustrated in Fig. 6.2. 

Therapeutic Function Cancer chemotherapy Chemical Name 2a-Methyl-17 5-(l-oxopropoxy)-5a-androstan-3-one Common Name 2-Methyldihydrotestosterone propionate Structural Formula ... 

Fig. 7 Chemical structures of 5a-androstan-17(3-ol-3-one-2, 2, 4, 4-D4 (a) and 5a-androstan-17pl-ol-3-one-16, 16, 17-D3 (b) and schematic representation showing how deuterium-hydrogen exchange occurs during keto- and enol- form conversions (c)...

Another example is illustrated in Fig. 1.3. Testosterone and epitestosterone are eluted as one peak using SE-30 as the stationary phase. By conversion of the hydroxyl group into a more bulky substituent, the slight difference in the structure is enhanced and the two epimers can be resolved. The same approach can be used for the separation of 16-and 15-keto isomers of androstan-30-ol. The initial ketones are not separated on SE-30, but after conversion into the corresponding N,N-dimethylhydrazones their separation is possible as these derivatives are eluted much more slowly than the initial compounds [3]. 

Most steroids have an oxygen functional group (=0 or —OH) at C3 and some kind of side chain or other functional group at Cl7. Many also have a double bond from C5 to either C4 or C6. The structures of androsterone and cholesterol serve as examples. Androsterone, a male sex hormone, is based on the simple androstane ring system. Cholesterol is a common biological intermediate and is believed to be the biosynthetic precursor to other steroids. It has a side chain at C17 and a double bond between C5 and C6. 

A compound whose structure is based on the tetracyclic androstane ring system, (p. 1210)... 

Full particulars have been published of the very ready aromatization of 2/3-hydroxy-19-oxoandrost-4-ene-3,17-dione in neutral aqueous media.222 Slight alkalinity accelerates the reaction possible mechanisms are discussed. 4/3,5-Epoxy-6a-hydroxy-5)8-androstan-17/8-yl acetate and 2a,3a-epoxy-6/8-hydroxy-5a-androstan-17/3-yl acetate are new additions223 to the long list of A/B-trifunctional steroids which aromatize to give 4-methyloestra-l,3,5(10)-trienes in HBr-AcOH.224 A new route to anthrasteroids comprises the conversion of a 5,7-diene into its adduct (271) with 4-phenyl-l,2,4-triazoline-3,5-dione and reaction of the adduct with boron trifluoride etherate.225 The structure (272) of the product was established by X-ray crystallography. 

The structures of the 9-methyl-5a,9j8,10a-oestran-3-one (1) and its 2a- and 2/8-bromo-derivatives have been studied by X-ray crystallography. Ring A in the 2/8-bromo-compound is forced into a twist-boat conformation by steric compression (2/8-Br/9/3-Me), but the other two compounds are only slightly deformed from the chair conformation. These findings are compatible with the properties (c.d. and n.m.r.) of the same compounds in solution. 3a-Acetoxy-4a,8a,14/8-trimethyl-18-nor-5a,9/3,13a-androstan-17-one (2), another steroid of unusual configuration, derived from fusidic acid, has a twisted boat conformation of ring B. ... 

Figure 6.4 Chemical structures of estranes, androstanes, cardiac glycosides steroid saponins and steroid alkaloids mentioned in the text.

Microbial transformation of unnatural steroid structures, such as 5/ ,14/ -androstane-3,17-dione (1) with Cercospora melonis afforded 14/J-hydroxylated material along with byproducts112. 

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