The purpose of this research has been to synthesise some
new compounds which are useful standards in the identification
of naturally occurring steroids of unknown structure.
The work has been divided into three parts, the synthesis
of 11-oxygenated counterparts of the 3ß-hydroxy-Δ⁵ steroids which
have already been found in the processed urine of newborn infants,
the synthesis of 15,17-disubstituted 3ß-hydroxy-Δ⁵ steroids and
the synthesis of 3ß,18-dihydroxyandrost-5-en-17-one and 3ßhydroxy
-18 nor-13α-androst-5-en-17-one.
The synthesis of the 11-oxygenated counterparts of the known
3ß-hydroxy-Δ⁵ steroids has involved the development of an efficient
method for converting the 3-keto-z4 structure into the 3ß-hydroxy-Δ⁵ system. This has been achieved by the reaction of the conjugated
enone with strong base in dimethylsulphoxide and the
quenching of this reaction mixture with aqueous methanolic
borohydride solution. The preparation from adrenosterone of 3ß,
16α-dihydroxyandrost-5-ene-11, 17-dione and the corresponding
11ß-alcohol is described.
The route to 3ß-hydroxy-Δ⁵ steroids from the sapogenin
derivative 3ß,12ß-diacetoxy-25R,S-spirost-5-en-11-one has been
used to synthesise 3ß,16α-dihydroxypregn-5-ene-11,20-dione and
3ß,21-diacetoxypregn-5-ene-11,20-dione.
In the synthesis of 15,17-disubstituted steroids suitably
protected Δ¹⁴ compounds were prepared via the intermediate
Δ¹⁵-17-ketone and the action of diborane on these compounds was
investigated. 3ß,15α,17ß-Trihydroxyandrost-5-ene was prepared
in a 1:1 mixture with 3ß,15ß,17ß-trihydroxy-14ß-androst-5-ene.
3ß,15ß,17ß-Trihydroxyandrost-5-ene has been synthesised by way
of the intermediate 15ß benzyloxy-17-keto compound.
The synthesis of 3ß-hydroxy-Δ⁵ steroids substituted at the
C-18 position has been investigated. 3ß-Acetoxy-18-hydroxypregn-
5-en-20-one hemiacetal has been prepared from pregnenolone by the
'hypoiodite' reaction. This intermediate was used to synthesise
3ß,18-dihydroxyandrost-5-en-17-one.
3ß-Hydroxy-18-nor-13α-androst-5-en-17-one has been prepared
by the sublimation of 3ß,18-dihydroxyandrost-5-en-17-one at 230°.
The 13α-configuration of the isolated product has been deduced by
optical rotatory dispersion studies
