Base promoted air oxidation of 13beta-ethyl-11-methylenegon-4-en-17-one.
The structure of 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-16beta,17-diol (3, 16beta-OH desogestrel), a by-product obtained in the last step of the synthesis of desogestrel (1) by reaction of monolithium acetylide-ethylenediamine complex with 13beta-ethyl-11-methylenegon-4-en-17-one (2), is here reported. The structural assignments were supported by NMR 1H-, 13C-, 1H-1H COSY, 1H-13C HSQC, COLOC) and mass spectroscopy, and the configuration at the C-16 and C-17 stereocentres was established by X-ray crystallography. When the same 17-ketoderivative 2 was treated with a non-alkylating base, such as potassium tert-butoxide, instead of the expected 16-hydroxylated ketone, a dimeric product, 13beta-ethyl-16-[2'-(des-D-13"-carboxy-13"beta-ethyl-11"-methylenegon-4"-en-14"-yl)-ethyliden]-11-methylenegon-4-en-17-one (4), was isolated in good yield; it was characterized by NMR, mass, ultraviolet spectroscopy, and chemical transformations. Compounds 3 and 4 originate from the high reactivity of the 16-methylenic position of the 17-keto substrate (2) toward molecular oxygen under basic conditions.
Compostella
Federica
F
Dipartimento di Chimica e Biochimica Medica, Università di Milano, Via Saldini 50, 20133 Milano, Italy.
Colombo
Diego
D
Modica
Emilia
E
Antonio Scala
Toma
Lucio
L
Bovio
Bruna
B
Ronchetti
Fiamma
F
D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D017135:Desogestrel / Q000138:chemical synthesis / Q000737:chemistry*; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D013256:Steroids / Q000737:chemistry*
C450320:13-ethyl-11-methylenegon-4-en-17-one; D013256:Steroids; D017135:Desogestrel