Androsta-4,16-diene-3-one

Iodine azide is a highly selective reagent addition to the 16-double bond of androsta-4,16-diene-3-ones is possible and some selectivity in addition to the 16-double bond of A -dienes has been observed.Hydroxy groups in the steroid should be protected, e.g., by acetylation, since in some instances oxidized side products are formed. 

Not only the sensitivity of the human olfactory system to androstenol (5a-androst-16-en-3a-ol) and androstenone (5a-androst-16-en-3-one),but also the difference in the sensitivity with which individuals can detect these compounds and the fact that they are implicated in the semiochemical communication of the pig, Sus scrofa [166,167], have led to them being considered human pheromones. Final confirmation that they are human pheromones is still outstanding. However, it was recently found that passive inhalation of another related steroid, androsta-4,16-dien-3-one, can influence the physiological state of humans by increasing a positive mood in test persons [168]. It has yet to be determined whether humans exude concentrations of this chemical information that are adequate for communication within social contexts. 

But men also have their chemical appeal. Their 5a-androst-16-en-3-one and androsta-4,16-dien-3-one act as attractants for women. Tests have been carried out, whereby it was observed that women - without being aware of their selection - prefer to sit on chairs, which have been doped with these substances. 

More recently it was foundthat also androsta-4,16-dien-3-one, a metabolite of testosterone as well, has strong pheromone-like activities in humans. It affects significantly the mood of heterosexual women andhomosexual men, but it does not alter behavior overtly, although it may have more subtle effects on attention. Androstadienone is commonly sold in male fragrances, in order to increase sexual attraction. [17]... 

The putative human pheromone androsta-4,16-dien-3-one and civetone are structurally closely related. 

Brooksbank, B. W. L. Androsta-4,16-diene-3-one in Peripheral Plasma of Adult Men... 

Most dienones that have been reduced have structures such that they cannot give epimeric products. However, reduction of 17 -hydroxy-7,17a-dimethyl-androsta-4,6-dien-3-one (63) affords 17 -hydroxy-7j9,17a-dimethylandrost-4-en-3-one (64), the thermodynamically most stable product, albeit in only 16% yield. The remainder of the reduction product was not identified. Presumably the same stereoelectronic factors that control protonation of the / -carbon of the allyl carbanion formed from an enone control the stereochemistry of the protonation of the (5-carbon of the dienyl carbanion formed from a linear dienone. The formation of the 7 -methyl compound from compound (63) would be expected on this basis. 

Sensitized photo-oxygenation of 5a-androsta-14,16-diene (105) gave the 14/3-hydroxy-15-en-17-one (106).118 The 14,16-diene was obtained by allylic bromina-tion of the 16-ene and dehydrobromination with l,5-diazabicyclo[5,4,0]undec-5-ene. Other bases were less efficient. 

Androsta-l,4-diene-3,17-dione reacted selectively at C-17 with potassium acetylide to give the 17a-ethynyl-17/8-alcohol the dihydroxyacetone side-chain was then elaborated by use of known transformations, without interference from the l,4-dien-3-one system/ Ethynylation of a [16- H]- or [16- H2]-17-oxo-steroid proceeds without loss of label/ ... 

The introduction of a double bond between C-9 and C-11 into the testosterone nucleus as in case of 17a-methylandrosta-4,9(ll)-dien-17P-ol-3-one (Fig. 3.6,7) causes a considerable change of the fragmentation pathway compared for instance to androsta-4,6-dien-17P-ol-3-one. While the molecular ion of androsta-4,6-dien-17P-ol-3-one is base peak in the respective El mass spectrum, the dissociation of 17a-methyl-androsta-4,9(ll)-dien-17P-ol-3-one yields predominantly ions at m/z 242 and 227 on expense of the relative abundance of its molecular ion. The elimination of the entire steroidal D-ring or major parts including C-16 and C-17 were proposed to establish suitable leaving groups generating the intense peaks (M -58) and (M -73) in the spectrum of 17a-methyl-androsta-4,9(ll)-dien-17P-ol-3-one (Table 3.3). ... 

Figure 4.5 Structures of selected steroidal analytes 5a-androstan-17P-ol-3-one (1), 5P-androstan-17P-ol-3-one (2), 17a-methyl-5a-androstan-17P-ol-3-one (3), la-methyl-5a-androstan-17P-ol-3-one (4), testosterone (5), nandrolone (6), 1-testosterone (7), metenolone (8), 5a-androst-l-ene-3,17-dione (9), metandienone (10), 18-nor-17P-hydroxymethyl,17a-methyl-androst-l,4,13-trien-3-one (metandienone metabolite) (11), androsta-4,6-dien-17P-ol-3-one (12), androsta-4,9-dien-17P-ol-3-one (13), trenbo-lone (14), methyltrienolone (15), tetrahydrogestrinone (THG, 16), and stanozolol (17).

With dienones exchange of all potentially activated hydrogens is less certain. For example, in alkaline medium, androsta-3,5-dien-7-one (26) undergoes complete exchange,16 while only the 2,2,4-trideutero derivative... 

ZnCl2-acetic acid added to a soln. of androsta-l,4-diene-3,16-dione in acetic anhydride, and allowed to stand at room temp, under Ng overnight -> 1-acetoxy-4-methylestra-l,3,5(10)-trien-16-one. Y 98.4%. K. Sasaki et al., Chem. Pharm. Bull. 18, 2018 (1970). 

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