Gerster J F, Rohlfing S R, Pecore S E, Winandy R M, Stern R M, Landmesser J E, Olsen R A, Gleason W B
J Med Chem. 1987 May;30(5):839-43. doi: 10.1021/jm00388a016.
The tricyclic quinolone antibacterial agent 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo[ij]quinolizine -2-carboxylic acid has an asymmetric center at position 5 of the molecule. The R and S isomers of the compound have been prepared from the corresponding (R)- and (S)-2,5-dimethyl-6-fluoro-1,2,3,4-tetrahydroquinolines, which were separated via their diastereomeric amides of N-tosyl-(S)-proline. The absolute configuration was established by X-ray analysis of one of the diastereomeric amides. The 5-desmethyl analogue was prepared for antibacterial comparison with the isomers and the racemic mixture. It has now been established that the S isomer is much more active than the R isomer. The 5-desmethyl analogue was found to be more active than the R isomer but not as active as the S isomer or the racemic mixture. The importance of stereochemistry at position 5 in this system has been established.
三环喹诺酮抗菌剂6,7-二氢-5,8-二甲基-9-氟-1-氧代-1H,5H-苯并[ij]喹嗪-2-羧酸在分子的5位有一个不对称中心。该化合物的R和S异构体由相应的(R)-和(S)-2,5-二甲基-6-氟-1,2,3,4-四氢喹啉制备，它们通过N-对甲苯磺酰基-(S)-脯氨酸的非对映体酰胺进行分离。通过对其中一种非对映体酰胺进行X射线分析确定了绝对构型。制备了5-去甲基类似物，用于与异构体和外消旋混合物进行抗菌比较。现已确定S异构体比R异构体活性高得多。发现5-去甲基类似物比R异构体活性高，但不如S异构体或外消旋混合物活性高。已确定该体系中5位立体化学的重要性。
