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The sequential reaction of 3β-acetoxypregna-5,16-dien-20-one (1) with methylmagnesium bromide and then methyl iodide has been examined in detail. The major product (85%) was 3β-hydroxy-16α,17α-dimethylpregn-5-en-20-one (2). Other products identified were 3β-hydroxy-16α-methylpregn-5-en-20-one (4); the 21-methyl derivatives [(5) and (10)] of (2) and (4); the 21-(1-hydroxy-1-methylethyl) derivative (11) of (2); and a trace of the 21,21-dimethyl derivative (12) of (2). The scope of the reaction with regard to the range of substituents that can be introduced at positions 16 and 17 has been established by preparing a series of 16α-substituted 17α-methylpregnenolones with a variety of alkyl, aryl, and aralkyl groups. Some of these have been converted into the corresponding 16α,17α-disubstituted progesterones.

The development of a 21-alkylation reaction which proceeds via the lithium 20(21)-enolate is described and its scope demonstrated by the preparation of a variety of 21-alkylpregnane derivatives. Application of this process to 11β-acetoxy-16α,17α-dimethyl-5α-pregnane-3,20-dione (28a) and its 5β-analogue (28b) led to the corresponding 16α,17α,21-trimethyl derivatives. Several routes from these saturated trimethylpregnane-3,20-diones to 11β-hydroxy-16α,17α,21-trimethylpregna-1,4-diene-3,20-dione (Org 6216) were explored. The best method gave Org 6216 in 75% yield.

Use of the skeletal rearrangement and the hydrogenolysis of n-hexane as probe reactions, and interaction with titania as a means of modifying catalytic properties, has provided evidence that the active centre in Pt catalysts consists of only a single metal atom in a unique environment.

Periodic acid smoothly regenerates a variety of steroidal ketones from their thioacetals at room temperature in common solvents and generally in high yield.