Seco compounds from the class of tylosins

Process for the preparation of compounds of a general formula I ##STR5## wherein R stands for H or CH.sub.3,

• R.sup.1 stands for H, CH.sub.3, C.sub.1 -C.sub.3 acyl or aryl sulfonyl,
• R.sup.2 stands for H and R.sup.3 stands for NH.sub.2 or OH, or R.sup.2 and R.sup.3 together stand for .dbd.O or .dbd.NOH,
• R.sup.4 stands for H or C.sub.1 -C.sub.3 acyl,
• and the line - - - stands for a double or a single bond,
• wherein 4'-demicarosyl-8a-aza-8a-homorelomycin of the formula II ##STR6## is subjected to A/ oximation with 3-10 equivalents of hydroxlyamine hydrochloride in pyridine in a nitrogen stream at reflux temperature during 3 to 10 hours, whereby a compound of formula I is obtained, wherein R, R.sup.1 and R.sup.4 are the same and stand for H, R.sup.2 and R.sup.3 together stand for .dbd.NOH and the line - - - stands for a double bond which is then optionally
• A1/ reductively N-alkylated with 1-4 equivalents of formaldehyde (36% w/v) in the presence of the 1-5 equivalents of formic acid (98-100% wv) in halogenated hydrocarbons, such as chloroform or methylene chloride, at a temperature from 10.degree. C. to reflux temperature during 2 to 30 hours, whereby a compound of formula I is obtained, wherein R and R.sup.1 are the same and stand for CH.sub.3, R.sup.2 and R.sup.3 together stand for .dbd.NOH, R.sup.4 stands for H and the line - - - stands for a double bond;
• or a compound obtained by process A is, optionally, subjected to
• A2/ a catalytic hydrogenation in C.sub.1 -C.sub.3 aliphatic alcohol in the presence of a noble metal on an inert carrier at a hydrogen pressure from 0.2 to 0.5 MPa and at room temperature during 2 to 10 hours, whereby a compound of formula I is obtained, wherein R, R.sup.1 and R.sup.4 are the same and stand for H, R.sup.2 and R.sup.3 together stand for .dbd.NOH and the line - - - stands for a single bond;
• or a compound obtained by process A is optionally subjected to
• B/ conversion of hydroxyimino group into keto group with NaHSO.sub.3 in the presence of an acid in 50% ethanol, at reflux temperature during 2 to 8 hours, whereby a compound of formula I is obtained wherein R, R.sup.1 and R.sup.4 are the same and stand for H, R.sup.2 and R.sup.3 together stand for .dbd.O and the line - - - stands for a double bond, which is then optionally subjected to
• B1/ a reaction of N- or N,O-acylation with C.sub.1 -C.sub.3 carboxylic acids in a halogenated hydrocarbon at room temperature or reflux temperature during 1 to 20 hours, whereby a compound of a general formula I is obtained, wherein R and R.sup.4 are the same and stand for H, R.sup.1 stands for CHO, R.sup.2 and R.sup.3 together stand for .dbd.O and the line - - - stands for a double bond, and a compound of the formula I, wherein R stands for H, R.sup.1 and R.sup.4 are the same and stand for COCH.sub.3, R.sup.2 and R.sup.3 together stand for .dbd.O and the line - - - stands for a double bond, which is then optionally subjected to
• B1/1 methanolysis at room temperature during 3 days, yielding a compound of a general formula I, wherein R and R.sup.4 are the same and stand for H, R.sup.1 stands for COCH.sub.3, R.sup.2 and R.sup.3 together stand for .dbd.O and the line - - - stands for a double bond;
• or a compound obtained by process B is optionally subjected to
• B2/ catalytic hydrogenation in the manner described in A2, whereby a compound of formula I is obtained, wherein R, R.sup.1 and R.sup.4 are the same and stand for H, R.sup.2 and R.sup.3 together stand for .dbd.O and the line - - - stands for a single bond;
• or a compound obtained by process B is optionally, subjected to
• C/ a reduction with NaBH.sub.4 in a C.sub.1 -C.sub.3 aliphatic alcohol at room temperature during 0.5 to 2 hours, whereby a compound of formula I is obtained, wherein R, R.sup.1, R.sup.2 and R.sup.4 are the same and stand for H, R.sup.3 stands for OH and the line - - - stands for a double bond, which is optionally subjected to
• C1/ N-tosylation with p-toluene sulfochloride in pyridine at room temperature during 1 to 5 hours, whereby a compound of formula I is obtained, wherein R, R.sup.2 and R.sup.4 are the same and stand for H, R.sup.1 stands for tosyl, R.sup.3 stands for OH and the line - - - stands for a double bond,
• or a compound obtained by process C is optionally subjected to
• C2/ reductive N-alkylation in the manner described in A1, whereby a compound of formula I is obtained, wherein R and R.sup.1 are the same and stand for CH.sub.3, R.sup.2 and R.sup.4 are the same and stand for H, R.sup.3 stands for OH and the line - - - stands for a double bond;
• or a compound obtained by process C is optionally subjected to
• C3/ catalytic hydrogenation in the manner described in A2, whereby a compound of formula I is obtained, wherein R, R.sup.1, R.sup.2 and R.sup.4 are the same and stand for H, R.sup.3 stands for OH and the line - - - stands for a single bond, which is optionally
• C4/ N-alkylated in the manner described in A1, whereby a compound of formula I is obtained, wherein R and R.sup.1 are the same and stand for CH.sub.3, R.sup.2 and R.sup.4 are the same and stand for H, R.sup.3 stands for OH and the line - - - stands for a single bond;
• or a compound obtained by process A is optionally
• D/ subjected to catalytic reduction in glacial acetic acid in the presence of noble metals and their oxides as catalysts at a hydrogen pressure from 5.07 to 70.93 bars and at room temperature during 10 hours to 3 days, whereby a compound of formula I is obtained, wherein R, R.sup.1, R.sup.2 and R.sup.4 are the same and stand for H, R.sup.3 stands for NH.sub.2 and the line - - - stands for a single bond;
• or a compound obtained by process A is optionally subjected to
• E/ an electrochemical reduction in an electrolytic H-cell with anode and cathode regions separated by a membrane, using a Hg basin as the working electrode and graphite as the counter electrode, in a phosphate buffer with pH 4.0-7.0 at a constant potential between 1.2-1.6 V against saturated calomel electrode during 1 to 5 hours at room temperature in a nitrogen stream, whereby a compound of formula I is obtained, wherein R, R.sup.1, R.sup.2 and R.sup.4 are the same and stand for H, R.sup.3 stands for NH.sub.2 and line - - - stands for a double bond.