GB1065715A - Tetracycline derivatives - Google Patents

Abstract

The invention relates to tetracycline compounds having the following formulae <FORM:1065715/C2/1> wherein R1 is H, benzyl, phenethyl, cyclohexyl or C2- 6 alkyl, R2 is H, hydroxy -C2- 6 alkyl or C2- 6 alkyl; and when R1 or R2 is H, the other R is other than H, X is H or CH3, X1 is OH, or X and X1 together are methylene, or X1 represents a second bond connecting C6 and C5a, X2 is H or OH, X being CH3 when the C6-C5a bond is a single bond and/or X2 is OH, and Y is H or chloro, <FORM:1065715/C2/2> wherein at least one of R1 and R2 is H, X, X2, Y and R1 and R2 having the above meanings, and also to their salts. Compounds of Formula I are prepared by alkylating a compound of Formula II, e.g. by means of an alkyl, hydroxyalkyl, alicylic or aralkyl iodide or alkyl sulphate in the presence of an acid acceptor (base) or acid scavenger (propylene oxide). Alternatively, an aldehyde or ketone in the presence of a reducing agent and a catalyst may be used. Compounds of general Formula II are prepared by reacting a compound of Formula III <FORM:1065715/C2/3> in which X, X1, X2 and Y are as defined above, Z is H, Cl or F, X being CH3 when the 6-5a bond is a single bond and Z is H, or Z is halogen when X and X1 are together methylene, and when X1 is OH, the compound III being also in its 4-6 hemiketal form, with ammonia or a primary amine under reductive amination conditions; or with a compound H2NR3 wherein R3 is OH, NHCONH2, NHC(NH)NH2, NHCSNH2, 4-(beta-hydroxyethyl) piperazino or NR4R5 wherein R4 is H, C1- 6\ alkyl, phenyl, benzyl or cyclohexyl and R5 is H, C1- 6 alkyl, phenyl or benzyl, said compound of formula H2NR3 being reacted as a free base or as its acid salt and, if one of the reactants is a compound of formula H2NR3, reducing the reaction product.