Biomimetic total synthesis of steroids, IX. Stereospecific synthesis of C‐homo‐19‐norsteroids

Abstract

Recueil des Travaux Chimiques des Pays-Bas, 10412. february 1985 59 further two times. The material thus obtained was dissolved in water (15 ml) and washed with diethyl ether (3 x 15 ml). The water layer was partly evaporated in vacuo (30°C) and thereafter lyophilized. 63 mg (89%) of a slightly yellow coloured fluffy material was obtained.TLC (cellulose F,,, , DC-Alufolien, Merck; solvent VI): major compound R, 0.72 (Ninh.+). Several minor compounds were detected. 7 was used without further purification. H-Ala-Ser(PGal)-Ala-OH (8)Hydrazine hydrate (97 ~1 , 2 . 0 mmol) was added to a stirred solution of 7 (58 mg, 0.1 mmol) in CH,OH (1.0 ml) at room temperature.After 40 min, the solution was cooled to O'C, 2,4-pentanedion (205 pl, 2.0 mmol) was added and stirring was continued at room temperature for 15 min. The solution was diluted with water (25 ml) and washed with CHCI, (3 x 10 ml). The water layer was partly vaporated in vacuo and thereafter lyophilized. The material thus obtained was purified by chromatography on a 60 x 1.5 cm column of Sephadex G-10 (Pharmacia). Elution was effected using water at a flow rate of 20 ml/h. Fractions of 5 ml were collected. Aliquots of each fraction were spotted on TLC plates. Spots were visualized with ninhydrine reagent and methanolic H,SO,. 8 (37.2 mg, 91 %) was obtained by lyophilization of fraction 8-12. Using 300 MHz 'H NMR, the purity was estimated to be over 97% ( a small quantity of aromatic material together with some uncompletely deacetylated glycopeptide were present). A sample of8 was purified by chromatography on a 20 x 0.3 cm CP-TM-Spher CIB HPLC column (Chrompack). Elution was effected using water at a flow rate of 0.5 ml/min. The eluate containing unretarded material (UV detection at 205 nm) was collected and lyophilized. TLC (Cellulmose F2',, DC-Alufolien, Merck): IV, R, 0.23; V, 0.12; VI, 0.21 (Ninh'). 100 MHz 13C NMR (D,O, pH 5.48 meter reading): F 105.4 (d, Gal C'); 63.7 (t, Gal C6); 71.0 (t, Ser Ca); 182.2, 173.6, 172.4 (3 x s, C = 0); 78.0, 75.3, 73.3, 71.3 (4 x. d, Gal carbons, probably C', C3, C2 and C', r e~p e c t i v e l y~~-~~) ; 56.4,53.8,51.7 (3 x d, amino acid C);