GB1065716A — Tetracycline derivatives and process for their preparation

USPTO Abstract

The invention relates to tetracycline compounds having the following formulae <FORM:1065716/C2/1> in which 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 Cl; and 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 may be in its 4-6 hemiketal form. <FORM:1065716/C2/2> wherein X, X1, X2 and Y have the aforesaid meanings <FORM:1065716/C2/3> wherein Z is H, Cl or F, X is CH3 or H, X2 is OH or H, with the proviso that X is CH3 when Z is H or X2 is OH; Y is H or Cl. Also their salts. Compounds of formula (A) are produced by reacting a compound of formula <FORM:1065716/C2/4> in which X, X1, X2, Y and Z have the aforesaid meanings, the 6-5a bond being a single bond, or in which the Z is halo and X1 is an oxygen connected to the 6 and 12 positions in a hemiketal bond, with a hydrocarbon dicarboxylic acid haloimide, e.g. N-chlorosuccinimide and, if X1 in compound III is a bond in the 6-5a position, dehydrating the product in which X1 is OH or an oxygen connected to C6 and C4 in a hemiketal bond. Compounds of formula (B) are produced by reducing compounds of formula (A), e.g. with alkali metal hydrosulphite in aqueous alcohol. The salts may be pharmaceutically acceptable, e.g. the sodium, potassium, magnesium, calcium, aluminium, zinc, iron and magnesium; metal chelates salts with amines. Barium and strontium salts may be used in the isolation and purification of these compounds.