Process for the production of ramoplanin-like amide derivatives
The invention regards a process for the production of ramoplanin-like derivatives of formula (I): RAMO-NC—CO—R (I), wherein the radical R represents a hydrocarbon radical and the portion RAMO-NH— represents deacylated ramoplanin, any of its factors or ramoplanose. The compound of Formula (I) are obtained by reacting a carboxylic acid R—COOH with deacylated ramoplanin, any of its factors or ramoplanose protected on the ornitine amino groups. New compounds wherein the hydrocarbon radical R is different form those characaterizing the ramoplanin and ramoplanose natural products and their tetrahydro-derivatives are calimed. The new compounds have the same or better antinfective activity, lower haemolytic effect and better tolerability profile than ramoplanin.
1. A ramoplanin derivative of the following formula
wherein X is selected from the group consisting of hydrogen, 2-α-D-mannopyranosyl, 2-O-α-D-mannopyranosyl-α-D-mannopyranosyl, and 2,3-O-di [α-D-mannopyranosyl]-α-D-mannopyranosyl;
Y is selected from the group consisting of hydrogen and an amino protecting group; and
R represents -A-R 6 radical, wherein A is a methylene radical or a bond directly connecting the radical R 6 with the carbonyl group, and wherein R 6 is phenyl or a napthyl radical, or an acid addition salt thereof.
2. The derivative of claim 1 , wherein the phenyl radical is optionally substituted with a substituent selected from the group consisting of methyl, ethyl, methoxy, ethoxy, and phenyl.
3. The derivative of claim 2 , wherein A is a methylene radical and R 6 is a phenyl radical substituted with a methyl.
4. The derivative of claim 3 , wherein R 6 is 2-methylphenyl.
5. The derivative of claim 1 , wherein X is 2-O-α-D-mannopyranosyl-α-D-mannopyranosyl.
6. The derivative of claim 1 , wherein Y is hydrogen.
7. A ramoplanin derivative of the formula (f)
wherein X is selected from the group consisting of hydrogen, 2-α-D -mannopyranosyl, 2-O-α-D-mannopyranosyl-α-D-mannopyranosyl, and 2,3-O -di[α-D-mannopyranosyl]-α-D-mannopyranosyl;
Y is selected from the group consisting of hydrogen and an amino protecting group; and
R is a phenyl optionally substituted with a substituent selected from the group consisting of methyl, ethyl, methoxy, ethoxy, and phenyl, or an acid addition salt thereof.
8. The derivative of claim 7 , wherein R is 2-methylphenyl.
9. The derivative of claim 7 , wherein X is 2-O-α-D-mannopyranosyl-α-D-mannopyranosyl.
10. The derivative of claim 7 , wherein Y is hydrogen.
11. A ramoplanin derivative of the formula
or an acid addition salt thereof.