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33404-78-3Relevant articles and documents
Full-synthesizing method of natural product (+)-negamycin
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Paragraph 0033; 0034; 0056; 0057; 0058, (2017/09/18)
The invention belongs to the technical field of organic synthesis, and specifically relates to a full-synthesizing method of natural product(+)-negamycin. The method utilizes Mannich reaction to construct a C3 position chiral center, nitrine functional group introduction is achieved in a later period of a synthetic route, and use of a lot of explosive and highly-toxic product of azide is avoided; (R)-(+)-3-hydroxyl-4-chlorobutyric acid ethyl ester, an Ellman reagent of (R)-(+)-methyl propane-2-sulfinamide and Mannich reaction are utilized to construct a C4 position chiral center, full synthesis is achieved through simple 8-step reaction, and total yield reaches 30%. The full-synthesizing method disclosed by the invention has the short synthetic route and simple after treatment, and raw material sources are provided for development of antibiotic medicines based on the (+)-negamycin.
A total synthesis of (+)-negamycin through isoxazolidine allylation
Bates, Roderick W.,Khanizeman, Rab'Iah Nisha,Hirao, Hajime,Tay, Yu Shan,Sae-Lao, Patcharaporn
, p. 4879 - 4884 (2014/07/07)
The β-amino acid antibiotic (+)-negamycin has been synthesised in ten steps from epichlorohydrin via Sakurai allylation of an isoxazolidine intermediate. The key allylation reaction proceeded with complete trans-selectivity, which is attributed to electrostatic attraction between the chlorine atom and the iminium ion in the Sakurai intermediate. This journal is the Partner Organisations 2014.
Asymmetric syntheses of (+)-negamycin, (+)-3-epi-negamycin and sperabillin C via lithium amide conjugate addition
Davies, Stephen G.,Ichihara, Osamu,Roberts, Paul M.,Thomson, James E.
, p. 216 - 227 (2011/03/17)
The chemo- and enantioselective reduction of ethyl 4-chloroacetoacetate and the diastereoselective conjugate addition of enantiopure lithium N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester have been used as the key steps in the total asymmetric syntheses of (+)-negamycin (in 13 steps and 24% overall yield), (+)-3-epi-negamycin (in 13 steps and 10% overall yield) and sperabillin C (in 17 steps and 13% overall yield) from commercially available starting materials.
Efficient total synthesis of (+)-negamycin, a potential chemotherapeutic agent for genetic diseases
Hayashi, Yoshio,Regnier, Thomas,Nishiguchi, Shigenobu,Sydnes, Magne O.,Hashimoto, Daisuke,Hasegawa, Junya,Katoh, Takahiro,Kajimoto, Tetsuya,Shiozuka, Masataka,Matsuda, Ryoichi,Node, Manabu,Kiso, Yoshiaki
supporting information; experimental part, p. 2379 - 2381 (2009/02/03)
Herein, we describe an efficient strategy for the total synthesis of (+)-negamycin using commercially available achiral N-Boc-2-aminoacetaldehyde as starting material with 42% overall yield for a limited number of steps. The Royal Society of Chemistry.
A simple and efficient approach to 1,3-aminoalcohols: application to the synthesis of (+)-negamycin
Naidu, S. Vasudeva,Kumar, Pradeep
, p. 3793 - 3796 (2008/02/06)
A short and practical enantioselective synthesis of (+)-negamycin has been achieved in high enantio- and diastereomeric excess using an iterative Jacobsen's hydrolytic kinetic resolution as the key step.
Administration of negamycin or deoxynegamycin for the treatment of bacterial infections
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, (2008/06/13)
The invention provides a method for treating bacterial infections. In one aspect, the invention comprises orally administering a pharmaceutical composition to an animal, wherein the composition comprises a pharmaceutically acceptable excipient and an antibacterial effective amount of negamycin, or a pharmaceutically acceptable salt, prodrug or isomer thereof. An aspect of the invention also relates to a method of treating a bacterial infection, wherein the method comprises intravenously administering a pharmaceutical composition to an animal, and wherein the composition comprises a pharmaceutically acceptable excipient and an antibacterial effective amount of deoxynegamycin, or a pharmaceutically acceptable salt, prodrug or isomer thereof. An aspect of the invention also relates to a method of treating a bacterial infection, wherein the method comprises administering to an animal an antibacterial effective amount of negamycin or deoxynegamycin, or a pharmaceutically acceptable salt, prodrug or isomer thereof, and wherein the infecting bacteria are selected from a group of bacteria consisting of the following: Acinetobacter baumanii, Citrobacter freundii, Enterobacter aerogenes, haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus MRSA, Staphylococcus aureus GISA, Staphylococcus epidermis, Streptococcus pneumoniae PenR, Streptococcus pneumoniae PenS and Streptococcus pyogenes.
N- and C-terminal modifications of negamycin
Raju,Mortell, Kathleen,Anandan, Sampathkumar,O'Dowd, Hardwin,Gao, Hongwu,Gomez, Marcela,Hackbarth, Corinne,Wu, Charlotte,Wang, Wen,Yuan, Zhengyu,White, Richard,Trias, Joaquim,Patel, Dinesh V.
, p. 2413 - 2418 (2007/10/03)
Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program. An orthogonally protected β-amino acid derivative 3a was synthesized and used in parallel synthesis of negamycin derivatives on solid support. This advanced intermediate was also used for N- and C-terminal modifications using solution-phase methodologies. The N-terminal modifications have resulted in the identification of active analogues, whereas the C-terminal modifications resulted in complete loss of antibacterial activity. The N-methyl negamycin analogue, 19a, inhibits protein synthesis (IC50=2.3 μM), has antibacterial activity (Escherichia coli, MIC=16 μg/mL), and is efficacious in an E. coli murine septicemia model (ED50=16.3 mg/kg).
Asymmetric synthesis of (+)-negamycin
Jain, Rajendra P.,Williams, Robert M.
, p. 6361 - 6365 (2007/10/03)
An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved, starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)- 5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2). The synthesis involved the stabilized Wittig olefination of the lactone carbonyl group of 2 and subsequent asymmetric hydrogenation to generate the corresponding all-syn oxazine 4 with excellent diastereoselectivity. Conversion of 4 into β-alkoxy imine 7 and subsequent CeCl3-promoted chelation-controlled allylation of 7 generated the corresponding homoallylamine 8 with good diatereoselectivity, which was readily converted into (+)-negamycin (1) in 25% overall yield over 11 steps.
Asymmetric synthesis of (+)-negamycin
Davies, Stephen G.,Ichihara, Osamu
, p. 1919 - 1922 (2007/10/03)
(+)-Negamycin was synthesised employing the highly diastereoselective conjugate addition of lithium (α-methylbenzyl)benzylamide in the key step. The synthesis was completed in 13 steps starting from ethyl 4-chloroacetoacetate with an overall yield of 24%.
Palladium(II)-Assisted Difunctionalization of Monoolefins: Total Synthesis of (+)-Negamycin and (-)-5-epi-Negamycin
Masters, John J.,Hegedus, Louis S.
, p. 4547 - 4554 (2007/10/02)
(+)-Negamycin and (-)-5-epi-negamycin were synthesized by a process involving the palladium(II)-assisted alkylation of an optically active ene carbamate followed by carbonylative coupling to a trialkylvinyltin.The synthesis of (+)-negamycin was completed in 15 steps with an overall yield of 13percent.The synthesis of (-)-5-epi-negamycin was completed in 12 steps with an overall yield of 20percent.In preparing these compounds, a highly diastereoselective reduction of an unsaturated ketone and an efficient intramolecular Mitsunobu reaction were also carried out.
