A new anti-MRSA dipeptide, TAN-1057 A

Synthesis of Derivatives of ω-Isocyanato-α-methylamino, ω-Ureido-α-methylamino, and Nα-Methyl-α, ω-diamino Acids

“…(4S)-4-(9-Fluorenylmethoxycarbonylamino)methyl-3-methyl-2,2-bis(tri¯uoromethyl)-1,3-oxazolidin-5-one (5a; C 22 H 18 F 6 ) 2 ), 120.9 (q, J 287 Hz, CF 3 ), 122.0 (q, J 295 Hz, CF 3 ), 120. 5, 125.5, 127.6, 128.2, 141.8, 144.1 (¯uorenyl) …”

First enantioselective synthesis of the novel antiinfective TAN-1057A via its aminomethyl-substituted dihydropyrimidinone heterocycle

“…1 These compounds were found to be highly active against methicillin-resistant Staphylococcus aureus (MRSA) strains. 1,2 Both main components of this mixture were found to be dipeptides with an (S)-b-homoarginine side chain attached to a dihydropyrimidinone heterocyclic moiety. 2 The Takeda group succeeded in separating the natural diastereomeric mixture of TAN-1057A/B (6.0 g) into two fractions and isolated TAN-1057A (1.56 g) and TAN-1057B (5 mg) as dihydrochlorides.…”

“…1,2 Both main components of this mixture were found to be dipeptides with an (S)-b-homoarginine side chain attached to a dihydropyrimidinone heterocyclic moiety. 2 The Takeda group succeeded in separating the natural diastereomeric mixture of TAN-1057A/B (6.0 g) into two fractions and isolated TAN-1057A (1.56 g) and TAN-1057B (5 mg) as dihydrochlorides. 2 The absolute configurations at C-5 for both epimers of TAN-1057A/B were assigned on the basis of the similarities in the CD spectra which were recorded for the product obtained by mild hydrolysis (2% aq.…”

“…2 The Takeda group succeeded in separating the natural diastereomeric mixture of TAN-1057A/B (6.0 g) into two fractions and isolated TAN-1057A (1.56 g) and TAN-1057B (5 mg) as dihydrochlorides. 2 The absolute configurations at C-5 for both epimers of TAN-1057A/B were assigned on the basis of the similarities in the CD spectra which were recorded for the product obtained by mild hydrolysis (2% aq. Na 2 CO 3 , 70 8C, 1 h) of TAN-1057A (acyclic dipeptide 2), and the model compound 3 with its known (S)-configuration at C-2 ( Fig.…”

Ribosomal Alterations Contribute to Bacterial Resistance against the Dipeptide Antibiotic TAN 1057

“…1). TAN 1057 displays in vitro (5) and in vivo (9) antibacterial activity against staphylococci, including methicillin-resistant Staphylococcus aureus strains. Its in vitro activity is excellent in synthetic medium and pure fetal calf serum (FCS), whereas in a standard assay medium such as Mueller-Hinton (MH) broth, the MICs increase 10-to 256-fold (e.g., the MICs against S. aureus P209 in AOAC and MH medium are 0.1 and 3.1 g/ml, respectively) (3,12).…”