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Synthesen von 20‐Carbaldehyden und 20‐Carbonitrilen der Pregnanreihe aus (20 S )‐20‐Hydroxymethylpregna‐1,4‐dien‐3‐on
Author(s) -
Krieg Reimar,
Schönecker Bruno
Publication year - 1994
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199419941012
Subject(s) - chemistry , acetal , aldehyde , epimer , stereoselectivity , trifluoroacetic acid , acetic acid , yield (engineering) , isomerization , reagent , chemoselectivity , organic chemistry , medicinal chemistry , stereochemistry , catalysis , materials science , metallurgy
Synthesis of 20‐Carbaldehydes and 20‐Carbonitriles of the Pregnane Series Starting with (20 S )‐20‐Hydroxymethylpregna‐1,4‐dien‐3‐one An efficient six‐step approach to 3‐protected (20 S )‐3β‐hydroxypregna‐1,5‐diene‐20‐carbaldehydes 8 with potential importance in the synthesis of vitamin D analogues was developed starting with (20 S )‐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 (20 S ) stereochemistry of 3 and 8a–d was elucidated by 1 H‐NMR investigations.