Hydrogenation of the ansa-Chain of Rifamycins. X-ray crystal structure of (16S)-16,17,18,19-tetrahydrorifamycin S |
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Authors: | Cecilia Bartolucci Luciano Cellai Patrizia Di Filippo Doriano Lamba Anna Laura Segre Armando Doriano Bianco Marcella Guiso Vinicio Pasquali Mario Brufani |
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Abstract: | The catalytic hydrogenation of rifamycin S ( 2 ) over Pd/C, followed by oxidation with K3Fe(CN)6], generates a pair of 16,17,18,19-tetrahydrorifamycins S ( 3/4 ), epimeric at C (16). The use of PtO2 as catalyst leads to the hydrogenation also of the C(28)?C(29) bond giving, after oxidation by K3Fe(CN)6], a mixture of the epimers (16R)- and (16S)-16,17,18,19,28,29-hexahydrorifamycins S ( 5/6 ). Furthermore, we synthesized the (16R)- and (16S)-3-bromo derivatives 7/8 and (16R)- and (16S)-3-(piperidin-1-yl) derivatives 9/10 . The determination of the X-ray crystal structure of the most abundant epimer 4 of the tetrahydrorifamycins allowed the assignment of the absolute configuration at C(16) of all derivative. A Structure-activity relationship study showed that in general the (16R)-epimers are more potent inhibitors of bacterial RNA polymerase than the (16S)-epimers. |
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