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.
Tertiary-butoxycarbonyl (Boc) – A strategic group for N-protection/deprotection in the synthesis of various natural/unnatural N-unprotected aminoacid cyanomethyl esters
Karmakar, Ananta,Basha, Mushkin,Venkatesh Babu,Botlagunta, Murali,Malik, Noormohamed Abdul,Rampulla, Richard,Mathur, Arvind,Gupta, Arun Kumar
supporting information, p. 4267 - 4271 (2018/11/03)
A number of cyanomethyl esters of natural/unnatural aminoacids with un-protected amino functionality were synthesized because of their synthetic and medicinal importance. Critical N-Boc deprotection methods in the presence of labile (hydrolytic sensitivity) cyanomethyl functionality were screened thoroughly and it was found that readily available 4M HCl in 1,4-dioxane solution (2–4 equiv); acetonitrile, 0 °C, 2–4 h was a suitable condition. This condition was generalized and successfully applied to a variety of alkyl, alkynyl, aryl, heteroaryl, benzyl, azido, spiro amino acid cyanomethylesters irrespective of the nature of the amine (primary or secondary) and the distance between the amine and ester group to achieve final deprotected amino esters with high yield, and purity compared to other commonly known N-protecting groups (Cbz, Fmoc, Ac, Bn, Bz etc.). It was also demonstrated that N-Boc protected aminoacid cyanomethylesters are stable enough to carry out further functionalization compared to N-unprotected counterparts.