1-Desamino-1-hydroxy and 1-desamino-1-epi-hydroxy-4,6-di-o-(aminoglycosyl)-1,3-diaminocyclitols; 1-desamino-1-oxo-4,6-di-o-(aminoglycosyl)-1,3-diaminocyclitols, intermediates and use as antibacterial agents

A 1-desamino-1-oxo derivative of a 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitol selected from the group consisting of:

• 1-desamino-1-oxo-3,2'-di-N-R-gentamicin A,
• 1-desamino-1-oxo-3,6'-di-N-R-gentamicin B,
• 1-desamino-1-oxo-3,6'-di-N-R-gentamicin B.sub.1,
• 1-desamino-1-oxo-3,2'-di-N-R-gentamicin C.sub.1,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-gentamicin C.sub.1a,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-gentamicin C.sub.2,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-gentamicin C.sub.2a,
• 1-desamino-1-oxo-3,2',-di-N-R-gentamicin C.sub.2b,
• 1-desamino-1-oxo-3,2'-di-N-R-gentamicin X.sub.2,
• 1-desamino-1-oxo-3,6',3"-tri-N-R-kanamycin A,
• 1-desamino-1-oxo-3,2',6',3"-tetra-N-R-kanamycin B,
• 1-desamino-1-oxo-3,2',6',3"-tetra-N-R-3',4'-dideoxykanamycin B,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-sisomicin,
• 1-desamino-1-oxo-3,2',6',3"-tetra-N-R-tobramycin,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-verdamicin,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-Antibiotic JI-20A,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-Antibiotic JI-20B,
• 1-desamino-1-oxo-3,2'-di-N-R-Antibiotic G-52,
• 1-desamino-1-oxo-3,2'-di-N-R-Antibiotic G-418,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-Antibiotic 66-40B,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-Antibiotic 66-40D,
• the 5-epi, 5-epi-azido-5-deoxy, 5-epi-amino-5-deoxy analogs of the foregoing;
• and
• 1-desamino-1-oxo-3,2',6'-tri-N-R-Antibiotic Mu-1,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-Antibiotic Mu-2,
• 1-desamino-1-oxo-3,2',6'-tri-N-R-Antibiotic Mu-4, and
• 1-desamino-1-oxo-3,5,2',6'-tetra-N-R-Antibiotic Mu-5;
• wherein R is an amino protecting group.

The process for the preparation of a compound selected from the group consisting of a 1-desamino-1-hydroxy, or a 1-desamino-1-epi-hydroxy derivative of a 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitol,

• which comprises reaction of a 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitol having an unsubstituted primary amine at position 1 and all other primary amines protected with an amino protecting group, with an oxidizing agent selected from the group consisting of 3,5-di-t-butyl-1,2-benzoquinone, mesitylglyoxal, 3-nitro-mesitylglyoxal, 3,5-dinitromesitylglyoxal, benzothiazole-2-carbaldehyde, 6-nitrobenzothiazole-2-carbaldehyde and 2-pyridine carboxaldehyde;
• followed by reaction in situ of the thereby formed 1-imine intermediate with acid in the range of pH 1-5;
• then reaction of the thereby formed poly-N-R-1-desamino-1-oxo-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitol with a hydride donor reducing agent selected from the group consisting of sodium cyanoborohyride, sodium borohydride, morpholinoborane, N,N-diethylanilinoborane, 9-BBN.RTM., diborane, K-selectride.RTM. and L-selectride .RTM.;
• followed by the removal of the amino protecting groups in the thereby formed product mixture comprising poly-N-R-1-desamino-1-hydroxy-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitol and poly-N-R-1-desamino-1-epi-hydroxy-4,6-di-O-(aminoglycosyl)-1,3-diaminocycl itol;
• wherein R is an amino protecting group.