Über den Verlauf der Umsetzung von Steroid‐3,5‐dienaminen mit Formaldehyd

Abstract

Reaction of steroidal 3,5‐dienamines (including 9β,10α‐ and 19‐nor‐compounds) with formaldehyde gave 6‐hydroxymethyl derivatives as major products. The latter compounds are valuable intermediates for the preparation of 6‐methyl‐3‐keto‐Δ4,6‐steroids.

Characterization of related impurities in megestrol acetate

“…The 13 C NMR spectrum revealed 25 signals including four methyls, one methoxyl, eight methylene, five methines, four quaternary carbons and three carbonyls. Comparison with reported data of the known compound, 17␣-acetoxy-6␣-hydroxylmethylpregna-4-ene-3,20-dione [5], showed that impurity 3 is its methyl ether. The relative stereochemistry at C-6 was determined based on the characteristic J H-4, H-6 long-range coupling constant: for H-6 in ␣ form, the signal in H-4 must be a single peak, while H-6 in ␤ form, H-4 are generally double-peak (J in ∼1.5 Hz).…”

Identification and Quantification of Novel Major Metabolites of the Steroidal Aromatase Inhibitor, Exemestane

“…Although the stereochemistry at the 6-position was not assigned in the current paper, we speculate the stereo orientation for the 6 substitute is “ α ” for both synthesized 6-EXE-cys and 6-17 β -DHE-cys based on the proton coupling constant between the proton at the 4-position and the proton at the 6-position of both EXE-cys and 17 β -DHE-cys conjugates. For 6-substituted steroids, long-distance coupling between H-4 and H-6 in 1 H NMR will be observed only when the 6-substituent is in the α position ( Chin and Warren, 1972 ; Schneider et al, 1973 ; Numazawa and Oshibe, 1994 ; Numazawa and Yamaguchi, 1998 ; Görlitzer et al, 2006 ). In an analysis of a series of 6-substituted phenylaliphatic steroids, Numazawa and Yamaguchi (1998) demonstrated that proton coupling between the hydrogens at the 4- and 6-positions was only observed for the 6 α -substituted, but not the 6 β -substituted, phenylaliphatic steroids.…”