Synthesis of new antimicrobial pyrrolo[2,1-a]isoquinolin-3-ones.
The attractive structure of the pyrroloisoquinoline moiety, together with its potential antimicrobial activity, encouraged us to prepare six 8-substituted and seven 8,9-disubstituted-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-3-ones in a few steps with good yields. We applied a convenient methodology via double intramolecular cyclization conducted by a Bischler-Napieralski cyclodehydration-imine reduction sequence, which is widely employed in the synthesis of isoquinoline alkaloids. Therefore, we synthesized three series of these pyrrolo[2,1-a]isoquinolin-3-ones characterized by the substituent at the 8-position or 8,9-positions of the aromatic ring: (a) different side chains are attached to an 8-OH group (series 1); (b) a chlorine atom is attached to the 8-position (series 2); and (c) 8- and 9-carbons are bearing an identical group (series 3). The compounds bearing a benzylic moiety at the 8-position, for example, 8-benzyloxy-pyrrolo[2,1-a]isoquinolin-3-one (1a) and 8-(4-fluorobenzyloxy)-pyrrolo[2,1-a]isoquinolin-3-one (1e), as well as, a 8-chloro-9-methoxy moiety including the 8-chloro-9-methoxy-pyrrolo[2,1-a]isoquinolin-3-one (2a), provided the most fungicide and bactericide agents, respectively.
Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, 46100 Burjassot, Valencia, Spain.
Laura
L
Moreno
Javier
J
Párraga
Abraham
A
Galán
Nuria
N
Cabedo
Jaime
J
Primo
Diego
D
Cortes
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
C578970:8-chloro-9-methoxypyrrolo(2,1-a)isoquinolin-3-one; D000890:Anti-Infective Agents; D007546:Isoquinolines; D011758:Pyrroles; C560364:pyrrolo(2,1-a)isoquinoline