Synthesis of paromomycin derivatives modified at C(5″) to selectively target bacterial rRNA

The furanosyl moiety (ring III) of C(6′)-deoxyparomomycin and paromomycin was modified in search of aminoglycoside antibiotics with altered selectivity. The key intermediates were the N-Boc-protected derivative of C(6′)-deoxyparomomycin and the benzylidene-protected paromomycin. Their H2C(5″)–OH group was oxidised with trichlorocyanuric acid or [bis(acetoxy)iodo]benzene in the presence of catalytic amounts of TEMPO to yield the corresponding aldehydes and acids, which were transformed into the protected alkoxy imines, amides and the amine. Standard deprotection gave the title compounds derived from C(6′)-deoxyparomomycin and derived from paromomycin that proved less active than paromomycin and its C(6′)-deoxy analogue.

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