The synthesis of 11,12a-dideoxy-4-dedimethylamino-5a,6-anhydrotetracyclines

✍ Scribed by A.I Gurevich; M.G Karapetyan; M.N Kolosov; V.G Korobko; V.V Onoprienko; M.M Shemyakin

• Publisher: Elsevier Science
• Year: 1964
• Tongue: French
• Weight: 194 KB
• Volume: 5
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)90399-x

✦ Synopsis

TKE development of methods for the CG-hydrcxylation of +chloro-5a,6-anhydrotetracycline (I; X = NMe2, Y = Cl, 2 3 0.R) ' and the C,2a-hydroxylaticn of various 12a4eoxytetracyclines, in particular (I; X = Y = Z = H) 2, has placed the 5a,6-anhydrotetracyclines (I) in the position of key intermediates in the total synthesis of naturally occurring tetracycline antibiotics. We therefore undertook a synthetic study of snhydrotetracyclines, beginning with the synthesis of 1l,12a4ideoqy-44edimethylamino-5a,6-.snbydrctetracyclines (XI) which is reported in this paper. * Part xXx1X in "Studies in the Tetracycline Series". Syntheeie of substituted mhydrotetracyclines No.15 Michael condensation of the unsaturated ketones (II) 3 and (III) 4 with ethyl sodiomalonate followed by dehydration with alcoholic H2S04 afforded the keto-diesters (IV) (yield 65 -SO$). Direct saponification of these esters proved unsatisfactory, the reverse Michael reaction taking place in the presence of alkali. Hence the keto-acids (V) were obtained b.g NaBH4 reduction of the keto-diesters (IV) followed by hydrolysis, decarbozqlation and H2Cr04 oxidation (total yield of (V) up to 70%).