This compound has been obtained by two related ways: 1. By direct condensation of rifamycin S (I) with 1-(2,4,6-trimethylphenyl)piperazine (II), followed by reduction of the quinone subunit to the target hydroquinone with sodium ascorbate. 2. The bromination of rifamycin S (I) with Br2/pyridine in DMF gives 3-bromorifamycin S (III), which is condensed with piperazine (II) and reduced to the target hydroquinone as before.
The cyclization of piperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives perhydropyrido[1,2-a]pyrazin-1-one (III), which is reduced with LiAlH4 to yield perhydropyrido[1,2-a]pyrazine (IV). The reaction of (IV) with NaNO2/HCl, followed by reduction with LiAlH4, affords perhydropyrido[1,2-a]pyrazin-2-amine (V), which is finally condensed with rifamicin SV-3-carbaldehyde (VI).
The cyclization of 5-ethylpiperidine-2-carboxylic acid ethyl ester (I) with aziridine (II) in ethanol gives 7-ethylperhydropyrido[1,2-a]pyrazin-1-one (III), which is reduced with LiAlH4 to yield 7-ethylperhydropyrido[1,2-a]pyrazine (IV). The reaction of (IV) with NaNO2/HCl, followed by reduction with LiAlH4, affords 7-ethylperhydropyrido[1,2-a]pyrazin-2-amine (V), which is finally condensed with rifamicin SV-3-carbaldehyde (VI).