Synthesis of 17-(2-Methoxy-3-oxazolin-4-yl)-, 17-(3-Oxazolin-4-yl)-, and 17-(2-Oxazolin-4-ylidene) Substituted Steroids and Their Use as Precursors of Corticosteroids

• Published in: Journal of organic chemistry Vol. 59; no. 19; pp. 5650 - 5657
• Main Authors: van Leusen, Daan, Batist, Jacobus N. M, Lei, Jia, van Echten, Erik, Brouwer, Antoon C, van Leusen, Albert M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.09.1994; Amer Chemical Soc
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Chemistry, Organic; Exact sciences and technology; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Steroids; SIDE-CHAINS; SULFONYLMETHYL ISOCYANIDES; CHEMISTRY; ELABORATION; Hydrolysis; Steroid; Five membered ring; Ketol; Ketone; Isocyanide; Oxazole derivatives; Formaldehyde; Oxygen nitrogen heterocycle; Methanol
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00098a024

17-(Isocyanotosylmethylene)steroids 4 are useful intermediates in the conversion of 17-oxosteroids into 17-(hydroxyacetyl)steroids. The 21-CH2OH group is effectively introduced by a base-mediated reaction of compounds 4 with formaldehyde and MeOH to give 17-(2-methoxy-3-oxazolin-4-yl) derivatives 12, which by acid hydrolysis give 17-(hydroxyacetyl)steroids 10 and 16 in high yields. Partial hydrolysis of the same oxazoline derivatives 12 provides the 17-(hydroxyacetyl) cortico side chain of 13 equipped with a formyl-protected hydroxy group. 3-Oxazolinyl and 2-oxazolinylidene steroid derivatives 19, 20, and 21, without a 2-methoxy substituent, are discussed as alternatives of 12.