198416-01-2Relevant academic research and scientific papers
First enantioselective synthesis of the novel antiinfective TAN-1057A via its aminomethyl-substituted dihydropyrimidinone heterocycle
Belov, Vladimir N.,Brands, Michael,Raddatz, Siegfried,Krüger, Jochen,Nikolskaya, Sofia,Sokolov, Viktor,De Meijere, Armin
, p. 7579 - 7589 (2007/10/03)
Enantiomerically pure N2-Z-N2-MeAsnOH [(S)-14], prepared in 8 steps (23% overall yield) from asparaginic acid, was first subjected to a Hofmann degradation with PhI(OCOCF3)2 yielding (S)-N2-Z-N2-methyl-2,3-diaminopropanoic acid [N2-Z-N2-Me-L-A2pr, (S)-15], and this in turn was protected to give N2-Z-N3-Boc-N2-Me-L- A2pr [(S)-17]. Condensation of (S)-17 with HNC(SMe)NHCONH2 followed by removal of the tert-butoxycarbonyl protecting group, cyclization and hydrogenolytic removal of the Z-group gave the heterocycle of TAN-1057A [(S)-1] with an e.e. of 87 in 36% yield [from (S)-14]. Coupling of (S)-1 with (S)-tris-Z-β-homoarginine (20a) in the presence of O-(7-azabenzotriazol-1- yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) and iPr2NEt in N,N-dimethylacetamide followed by hydrogenolysis afforded the most active A-diastereomer of the natural antibiotic TAN-1057 in 52% yield (from (S)-1 and 20a). Similarly, starting from (S)-1, a single diastereomer of the potent, less toxic TAN-1057A analogue 22b with a β-lysine side chain has been prepared. All described synthetic steps do not require column chromatography for purification of the products.
Total synthesis of the anti methicillin-resistant Staphylococcus aureus peptide antibiotics TAN-1057A-D
Yuan, Chenguang,Williams, Robert M.
, p. 11777 - 11784 (2007/10/03)
TAN-1057A-D, dipeptides isolated from bacteria Flexibacter sp. PK-74 and PK-176, are new antibiotics with potent antibacterial activity against methicillin-resistant Staphylococcus aureus. We describe, in detail, the total synthesis of TAN-1057A-D by a co
