- Total Synthesis of Ecumicin
-
The first total synthesis of the potent anti-mycobacterial cyclic depsipeptide natural product ecumicin is described. Synthesis was achieved via a solid-phase strategy, incorporating the synthetic non-proteinogenic amino acids N-methyl-4-methoxy-l-tryptophan and threo-β-hydroxy-l-phenylalanine into the growing linear peptide chain. The synthesis employed key on-resin esterification and dimethylation steps as well as a final macrolactamization between the unusual N-methyl-4-methoxy-l-tryptophan unit and a bulky N-methyl-l-valine residue. The synthetic natural product possessed potent antimycobacterial activity against the virulent H37Rv strain of Mycobacterium tuberculosis (MIC90 = 312 nM).
- Hawkins, Paige M. E.,Giltrap, Andrew M.,Nagalingam, Gayathri,Britton, Warwick J.,Payne, Richard J.
-
p. 1019 - 1022
(2018/02/23)
-
- CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF
-
The present technology relates to compounds, kits, compositions, and methods useful for the treatment of fibrotic disease. In some aspects, the present technology provides for treatment of various diseases or disorders associated or mediated, at least in part, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is generally applicable to compounds which inhibit myofibroblast differentiation.
- -
-
Paragraph 00468
(2017/09/27)
-
- Synthesis and evaluation of phenylalanine-derived trifluoromethyl ketones for peptide-based oxidation catalysis
-
We report the synthesis of phenylalanine-derived trifluoromethyl ketones for the in situ generation of dioxiranes for the purpose of oxidation catalysis. The key features of this synthesis include the use of a masked ketone strategy and a Negishi cross-coupling to access the parent amino acid. The derivatives can be readily incorporated into a peptide for use in oxidation chemistry and exhibit good stability and reactivity.
- Featherston, Aaron L.,Miller, Scott J.
-
supporting information
p. 4871 - 4874
(2016/10/04)
-
- Light-mediated deoxygenation of alcohols with a dimeric gold catalyst
-
A new protocol for the reductive deoxygenation of primary alcohols was explored. This photo-mediated method combines a novel approach to bromination of alcohols merged with the powerful reducing capability of [Au2(dppm)2]Cl2 [dppm = 1,1-bis(diphenylphosphino)methane] as a photoredox catalyst. The highly efficient methods discussed are marked by the use of UVA light-emitting diodes, which have significantly reduced reaction times and lowered setup cost.
- McCallum, Terry,Slavko, Ekaterina,Morin, Mathieu,Barriault, Louis
-
supporting information
p. 81 - 85
(2015/02/18)
-
- Synthesis of chiral Nβ-protected amino diselenides from the corresponding amino alkyl iodides using NaBH2Se3 as a selenating reagent and their conversion to seleninic acids
-
A convenient approach has been presented for the synthesis of Nβ-protected amino diselenides from the corresponding amino alkyl iodides using in situ generated NaBH2Se3 as an efficient selenating reagent. All the diselenid
- Panguluri, Nageswara Rao,Panduranga, Veladi,Prabhu, Girish,Vishwanatha,Sureshbabu, Vommina V.
-
p. 51807 - 51811
(2015/06/25)
-
- Development of the first and practical method for enantioselective synthesis of 10B-enriched p-borono-l-phenylalanine
-
At present p-(10B)borono-l-phenylalanine (l-10Bpa) is used clinically as an excellent 10B carrier for BNCT; however, its enantioselective synthesis has not been reported yet. The present Letter describes the first and prac
- Hattori, Yoshihide,Asano, Tomoyuki,Kirihata, Mitsunori,Yamaguchi, Yoshihiro,Wakamiya, Tateaki
-
p. 4977 - 4980
(2008/09/21)
-
- The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
-
Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors.
- Gauthier, Jacques Yves,Chauret, Nathalie,Cromlish, Wanda,Desmarais, Sylvie,Duong, Le T.,Falgueyret, Jean-Pierre,Kimmel, Donald B.,Lamontagne, Sonia,Leger, Serge,LeRiche, Tammy,Li, Chun Sing,Masse, Frederic,McKay, Daniel J.,Nicoll-Griffith, Deborah A.,Oballa, Renata M.,Palmer, James T.,Percival, M. David,Riendeau, Denis,Robichaud, Joel,Rodan, Gideon A.,Rodan, Sevgi B.,Seto, Carmai,Therien, Michel,Truong, Vouy-Linh,Venuti, Michael C.,Wesolowski, Gregg,Young, Robert N.,Zamboni, Robert,Black, W. Cameron
-
p. 923 - 928
(2008/12/22)
-
- Cathepsin cysteine protease inhibitors
-
This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
- -
-
-
- Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers
-
The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in which substituents have been introduced into the 3- and 4-positions of the lactone ring. These analogues have been screened for their ability to activate and inhibit a Vibrio fischeri LuxI/LuxR-derived quorum sensing reporter system.
- Olsen,Severinsen,Rasmussen,Hentzer,Givskov,Nielsen
-
p. 325 - 328
(2007/10/03)
-
- Convenient preparation of (R)- and (S)-1-(2-amino-3-iodo)propanol derivatives from (S)-serine: Application in radical addition reactions
-
An efficient three step synthesis of the (R)- and (S)-1-(2-amino-3-iodo)propanol derivatives 4 and 7 from (S) serine is proposed. Their use in radical reactions is illustrated.
- Maria,Da Silva,Fourrey,Machado,Robert-Gero
-
p. 3301 - 3302
(2007/10/02)
-