128779-47-5Relevant articles and documents
Developing Equipotent Teixobactin Analogues against Drug-Resistant Bacteria and Discovering a Hydrophobic Interaction between Lipid II and Teixobactin
Zong, Yu,Sun, Xiuyun,Gao, Hongying,Meyer, Kirsten J.,Lewis, Kim,Rao, Yu
, p. 3409 - 3421 (2018)
Teixobactin, targeting lipid II, represents a new class of antibiotics with novel structures and has excellent activity against Gram-positive pathogens. We developed a new convergent method to synthesize a series of teixobactin analogues and explored structure-activity relationships. We obtained equipotent and simplified teixobactin analogues, replacing the l-allo-enduracididine with lysine, substituting oxygen to nitrogen on threonine, and adding a phenyl group on the d-phenylalanine. On the basis of the antibacterial activities that resulted from corresponding modifications of the d-phenylalanine, we propose a hydrophobic interaction between lipid II and the N-terminal of teixobactin analogues, which we map out with our analogue 35. Finally, a representative analogue from our series showed high efficiency in a mouse model of Streptococcus pneumoniae septicemia.
Sacubitril intermediate as well as synthesis method and application thereof
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Paragraph 0078; 0082-0083; 0086-0087; 0090-0091, (2020/06/16)
The invention belongs to the technical field of medicine, and particularly relates to a sacubitril intermediate and a synthetic method and application thereof, wherein the synthetic method comprises the steps: taking D-biphenyl alanine as an initial raw material, and successively carrying out multiple reactions; and crystallizing and filtering to obtain (R)-2-(N-tert-butyloxycarbonylamino)biphenylpropanol. According to the sacubitril intermediate and the synthetic method and application thereof disclosed by the invention, D-biphenyl alanine is selected as an initial raw material; the subsequent added reactants are combined for successive reaction for multiple times; and finally, (R)-2-(N-tert-butyloxycarbonylamino)biphenyl propanol is synthesized. The reaction steps are simple and environment-friendly; industrial production is facilitated, particularly, the chemical purity of the product can reach 96% or above; the yield can reach 85% or above, and good industrial prospects are achieved; in addition, according to the synthetic method of (R)-2-(N-tert-butyloxycarbonylamino)biphenyl propanol, the recycled metal catalyst and concentrated filtrate can be recycled, the synthesis cost of (R)-2-(N-tert-butyloxycarbonylamino)biphenyl propanol is low, and industrial production is better facilitated.
NEW PROCESS FOR EARLY SACUBITRIL INTERMEDIATES
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, (2018/07/22)
The invention relates to a new enantioselective process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone.
