557090-55-8Relevant articles and documents
An inexpensive procedure for reductive aminations using dimethylamineborane on millimolar and molar scale
Ortmann, Regina,Schlitzer, Martin
, p. 1757 - 1759 (2009)
We have developed an inexpensive and easy procedure for reductive aminations using dimethylamineborane instead of cyanoborohydride. Dimethylamineborane is easily prepared from readily available inexpensive starting materials and can be used without isolat
Synthesis and antiplasmodial activity of novel fosmidomycin derivatives and conjugates with artemisinin and aminochloroquinoline
Antoniou, Antonia I.,Athanassopoulos, Constantinos M.,Baltas, Michel,Grellier, Philippe,Menendez, Christophe,Mouray, Elisabeth,Palla, Despina
, (2020/10/27)
Malaria, despite many efforts, remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by Plasmodium falciparum. The antibiotic fosmidomycin (FSM) is also known for its antimalarial activity by targeting the nonmevalonate isoprenoid synthesis pathway, which is essential for the malaria parasites but is absent in mammalians. In this study, we synthesized and evaluated against the chloroquine-resistant P. falciparum FcB1/Colombia strain, a series of FSM analogs, derivatives, and conjugates with other antimalarial agents, such as artemisinin (ART) and aminochloroquinoline (ACQ). The biological evaluation revealed four new compounds with higher antimalarial activity than FSM: two FSM-ACQ derivatives and two FSM-ART conjugates, with 3.5–5.4 and 41.5–23.1 times more potent activities than FSM, respectively.
Design of potential bisubstrate inhibitors against Mycobacterium tuberculosis (Mtb) 1-deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr)-evidence of a novel binding mode
San Jose, Geraldine,Jackson, Emily R.,Uh, Eugene,Johny, Chinchu,Haymond, Amanda,Lundberg, Lindsay,Pinkham, Chelsea,Kehn-Hall, Kylene,Boshoff, Helena I.,Couch, Robin D.,Dowd, Cynthia S.
, p. 1099 - 1104 (2013/07/26)
In most bacteria, the nonmevalonate pathway is used to synthesize isoprene units. Dxr, the second step in the pathway, catalyzes the NADPH-dependent reductive isomerization of 1-deoxy-d-xylulose-5-phosphate (DXP) to 2-C-methyl-d-erythritol-4-phosphate (MEP). Dxr is inhibited by natural products fosmidomycin and FR900098, which bind in the DXP binding site. These compounds, while potent inhibitors of Dxr, lack whole cell activity against Mycobacterium tuberculosis (Mtb) due to their polarity. Our goal was to use the Mtb Dxr-fosmidomycin co-crystal structure to design bisubstrate ligands to bind to both the DXP and NADPH sites. Such compounds would be expected to demonstrate improved whole cell activity due to increased lipophilicity. Two series of compounds were designed and synthesized. Compounds from both series inhibited Mtb Dxr. The most potent compound (8) has an IC50 of 17.8 μM. Analysis shows 8 binds to Mtb Dxr via a novel, non-bisubstrate mechanism. Further, the diethyl ester of 8 inhibits Mtb growth making this class of compounds interesting lead molecules in the search for new antitubercular agents.
Synthesis of antimalarial compounds fosmidomycin and FR900098 through N- or P-alkylation reactions
Suresh, Surisetti,Shyamraj, Dharavath,Larhed, Mats
, p. 1183 - 1188 (2013/03/14)
Two straightforward and convenient routes for the synthesis of the antimalarial agents FR900098 and fosmidomycin are described. In the key steps N- or P-alkylation reactions are used. The best overall yields of FR900098 and fosmidomycin in 15 mmol scale a
