Synthesen von 20‐Carbaldehyden und 20‐Carbonitrilen der Pregnanreihe aus (20S)‐20‐Hydroxymethylpregna‐1,4‐dien‐3‐on

Abstract

Synthesis of 20‐Carbaldehydes and 20‐Carbonitriles of the Pregnane Series Starting with (20S)‐20‐Hydroxymethylpregna‐1,4‐dien‐3‐oneAn efficient six‐step approach to 3‐protected (20S)‐3β‐hydroxypregna‐1,5‐diene‐20‐carbaldehydes 8 with potential importance in the synthesis of vitamin D analogues was developed starting with (20S)‐20‐hydroxymethylpregna‐1,4‐dien‐3‐one (1). Oxidation of the 22‐hydroxy group of 1 by means of periodinane 2 (Dess‐Martin reagent) furnished the aldehyde 3 without epimerization. 3 was protected selectively at C‐22 as dimethyl acetal 5. Isomerization to 6 and subsequent reduction of the 3‐carbonyl group with calcium borohydride furnished the 3β‐alcohol 7a with high stereoselectivity. Cleavage of the acetal to 8a occurred in a homogeneous solution of acetic acid in the presence of small amounts of water and trifluoroacetic acid. After protection of the 3‐OH group 8b–d were obtained in 54% overall yield. The in situ generated aldehyde N,N‐dimethylhydrazones of 3, 8a, and 8b were converted in high yields with excellent chemoselectivity into the nitriles 12, 15a, and 15b with magnesium monoperoxyphthalate hexahydrate. The uniform (20S) stereochemistry of 3 and 8a–d was elucidated by 1H‐NMR investigations.