Staphylococcus aureus total synthesis

Recently, the piperazine intermediate 15 for the total synthesis of (—)-lemon-omycin (9) was reported by Fukuyama et al. [14], (—)-Lemonomycin possesses interesting antibiotic activity against methiciUin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium, as well as cytotoxicity against the human colon tumor cell line HCT-116 [15]. The reaction of 2-isocyanoethyl phenyl carbonate 11 gave Ugi product 14, which was further transformed to a piperazine intermediate 15 (Scheme 2). 

Plusbacin Aj (21) and the derivatives A2-A4 and B1-B4 are lipodepsipeptides isolated from a strain numbered PB-6250 related to the genus Pseudomonas obtained from a soil sample collected in the Okinawa Pref., Japan [56]. These compounds contain arginine residue and lactone linkage with characteristic 3-hydroxy fatty acids [57] (Figure 10.6). Plusbacin A3 (22) showed inhibitory activity against methicilhn resistant Staphylococcus aureus [56,58]. Recent total synthesis of this compound was reported and the absolute configuration of the lactone residue was determined as R [59]. 

The compound 121 is the core stmcture of (+)-hongo-quercin A 126, a natural product isolated from an unidentified terrestrial fungus, and exhibits antibacterial properties toward methicUlin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. In order to complete the total synthesis of (+)-hongoquercin A 126, reduction of 122 with TFA/TESH, and saponification gave 126 as a single diastereomer (Scheme 12.29). 

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