7-Phenylplatensimycin and 11-methyl-7-phenylplatensimycin: More potent analogs of platensimycin

Modern Organic Synthesis with α-Diazocarbonyl Compounds

“…751 The "undesired" regioisomer 254 was later carried forward to the analogue isoplatensimycin, 752 and the route was further exploited to prepare several analogues of platensimycin. 753 Kanazawa and co-workers have described approaches to the antitumor agent camptothecin (263) and related structures. Chem.…”

Dialkylamino‐2,4‐dihydroxybenzoic Acids as Easily Synthesized Analogues of Platensimycin and Platencin with Comparable Antibacterial Properties

“…As most antibiotic pills used in the clinics typically contain about two hundred milligrams of active substances, the current chemical syntheses of platensimycin or analogues reported so far would not be economically viable. We, [34] the Nicolaou group [28] as well as others, [22,32] have reported SAR studies of platensimycin. These studies have revealed that although the tetracyclic core of platensimycin is mainly solvent exposed (see Figure 1), gross modification of this moiety usually abrogates the biological activity of the antibiotic.…”

“…MIC value of compounds 8, 20 and 21. (1) 1 (0.5, [1] 4 [22] ) 1 (0.1, [1] 1 [22] ) > 32 (À)-myrtemycin (8) structures of our analogues (aldehydes) are commercially available or it takes only a single step to make the required aldehydes from commercially available alcohols. Our active analogues are even better than cerulenin against B. subtilis.…”

“…Lee et al showed that the addition of a phenyl or methyl substituent to the tetracyclic core of platensimycin increased its antibiotic activity. [22] However, Lees analogues which have enhanced antibiotic activities are not readily prepared and are obtained after 15 total steps.…”

“…It is just over four years since a group at Merck reported the identification of a novel class of antibiotics called platensimycin [1] or platencin, [2] which are FabF/H inhibitors and therefore inhibit the synthesis of lipids used by bacteria to make cell membranes. In only four years since the seminal report by the Merck group, over 20 groups worldwide have reported the total [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] or enzymatic syntheses [20,21] of platensimycin/platencin or analogues [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] thereof, and about 12 papers [22,23,[28][29][30][31][32][33][34][36]…”