SYNTHESIS AND BIOLOGICAL EVALUAFION OF SOME NEW ALICYCLICSPIRO-2'-(l '^'-OXAZOLIDINE) DERIVATIVES Hassan M. Faidallah 1 ", E. M. Sharshira' (b) and Mohammed S. M. AL-SAADI (>) '"'Chemistry Department, Faculty of Medicine, University of King Abdulaziz, Jeddah 21589, Kingdom Saudi Arabia. ^'Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt; e-mail: dressamsharshira@yahoo. com Abstract: Condensation of cyclic ketones J. with ethänolamines gave the corresponding spiro-oxazolidines 2. The thioamides 3 were obtained in good yields through reaction of 2 with the appropriate isothiocyanate. Reaction of 2 with formaldehyde or acetaldehyde in the presence of the appropriate amine afforded the corresponding aminomethyl spiro-compounds 4 and 5 respectively, in excellent yields. The structures of the isolated compounds were fully determined by spectral methods. Antimicrobial activities of some oxazolidines were also discussed. Introduction Oxazolidines have attracted attention as a new class of orally active synthetic antibiotics with a unique mechanism of bacterial protein synthesis inhibition 1 " 5 . One of the early oxazolidinones studied in detail was DUP-721 (I) 6 (Figure 1) exhibiting a broad spectrum of antibacterial activity including activity against drug-resistant Gram positive bacteria as well as several anaerobes and Mycobacterium tuberculosis. However, further development of DUP-721 (I) was discontinued because of safety concerns in animal models. DUP-721 (I) Linezolid (II) Figure 1 Continued efforts led to the identification of Linezolid (II) 5 ' 7 ' 8 (Figure 1) with excellent activity against ever increasing Methicillin Resistant Staphylococcus aureus (MRSA) and with a better safety profile; Linezolid was approved for clinical use in 2001. Structural changes at oxazolidine ring including substituents 9 " 14 and degree of unsaturation 15 " 18 have also shown antimicrobial activity. These findings encouraged us to synthesize some novel spiro-oxazolidines for biological applications. 43