175164-50-8Relevant academic research and scientific papers
Divergent Synthesis of Aeruginosins Based on a C(sp3)￡H Activation Strategy
Dailler, David,Danoun, Grégory,Ourri, Benjamin,Baudoin, Olivier
, p. 9370 - 9379 (2015)
A general and scalable access to the aeruginosin family of marine natural products, exhibiting potent inhibitory activity against serine proteases, is reported. This was enabled by the strategic use of two recently implemented Pd-catalyzed C(sp3)￡H activation reactions. The first method allowed us to obtain the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second method provided a rapid and divergent access to various hydroxyphenyllactic (Hpla) subunits, including halogenated ones. This unique strategy, together with an optimization of the fragment coupling sequence allowed the synthesis of four aeruginosins, that is, 98A-C and 298A from the chiral pool. Among them, aeruginosin 298A was synthesized on an unprecedentedly large scale. In addition, halogenated aeruginosins 98A and 98C were synthesized for the first time, thanks to a fine-tuning of the final hydrogenation step. Go natural! A general and scalable access to the aeruginosin family of marine natural products (see graphic), exhibiting potent inhibitory activity against serine proteases, is described. The strategic use of two different Pd-catalyzed C(sp3)￡H activation reactions led to the synthesis of aeruginosins98A-C and 298A.
A general and scalable synthesis of aeruginosin marine natural products based on two strategic C(sp3)-H activation reactions
Dailler, David,Danoun, Grégory,Baudoin, Olivier
supporting information, p. 4919 - 4922 (2015/04/14)
An efficient and scalable access to the aeruginosin family of marine natural products, which exhibit potent inhibitory activity against serine proteases, is reported. This synthesis was enabled by the strategic use of two different, recently implemented C(sp3)-H activation reactions. The first method led to the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second one provided rapid and divergent access to the various hydroxyphenyllactic (Hpla) subunits. This strategy allowed the synthesis of the aeruginosins 98B and 298A, with the latter being obtained in unprecedentedly large quantities.
HIV PROTEASE INHIBITORS AND METHODS FOR USING
-
Page/Page column 32, (2011/06/10)
Compounds that inhibit proteolytic enzymes of Human Immunodeficiency Virus (HIV) are described. Preparation of the inhibitors, pharmaceutical compositions containing them, and uses of the compounds or compositions for the treatment of HIV infections are also described.
Synthetic studies directed toward guianolides: an organoiron route to the 5,7,5 tricyclic ring system
Gone, Jayapal Reddy,Wallock, Nathaniel J.,Lindeman, Sergey,Donaldson, William A.
scheme or table, p. 1023 - 1025 (2009/05/27)
A diastereoselective route to the 5,7,5-tricyclic core of the guianolides is presented. This route relies on Cope rearrangement of a divinylcyclopropane prepared by alkenyl Grignard addition to a (pentadienyl)iron(+1) cation, followed by oxidative decompl
Potent, plasmodium-selective farnesyltransferase inhibitors that arrest the growth of malaria parasites: Structure-activity relationships of ethylenediamine-analogue scaffolds and homology model validation
Fletcher, Steven,Cummings, Christopher G.,Rivas, Kasey,Katt, William P.,Hornéy, Carrie,Buckner, Frederick S.,Chakrabarti, Debopam,Sebti, Sa?d M.,Gelb, Michael H.,Van Voorhis, Wesley C.,Hamilton, Andrew D.
supporting information; experimental part, p. 5176 - 5197 (2009/07/01)
New chemotherapeutics are urgently needed to combat malaria. We previously reported on a novel series of antimalarial, ethylenediamine-based inhibitors of protein farnesyltransferase (PFT). In the current study, we designed and synthesized a series of second generation inhibitors, wherein the core ethylenediamine scaffold was varied in order to examine both the homology model of Plasmodium falciparum PFT (PfPFT) and our predicted inhibitor binding mode. We identified several PfPFT inhibitors (PfPFTIs) that are selective for PfPFT versus the mammalian isoform of the enzyme (up to 136-fold selectivity), that inhibit the malarial enzyme with IC50 values down to 1 nM, and that block the growth of P. falciparum in infected whole cells (erythrocytes) with ED50 values down to 55 nM. The structure-activity data for these second generation, ethylenediamine-inspired PFT inhibitors were rationalized by consideration of the X-ray crystal structure of mammalian PFT and the homology model of the malarial enzyme.
Potent HIV-1 protease inhibitors incorporating meso-bicyclic urethanes as P2-ligands: Structure-based design, synthesis, biological evaluation and protein-ligand X-ray studies
Ghosh, Arun K.,Gemma, Sandra,Takayama, Jun,Baldridge, Abigail,Leshchenko-Yashchuk, Sofiya,Miller, Heather B.,Wang, Yuan-Fang,Kovalevsky, Andrey Y.,Koh, Yashiro,Weber, Irene T.,Mitsuya, Hiroaki
experimental part, p. 3703 - 3713 (2009/02/05)
Recently, we designed a series of novel HIV-1 protease inhibitors incorporating a stereochemically defined bicyclic fused cyclopentyl (Cp-THF) urethane as the high affinity P2-ligand. Inhibitor 1 with this P2-ligand has shown very impressive potency again
