- Studies Toward the Total Synthesis and Stereochemical Assignment of Microspinosamide
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Efforts toward the total synthesis and stereochemical assignment of the cyclic depsipeptide natural product microspinosamide are described. A single diastereoisomer was targeted corresponding to the predicted structure of the natural product incorporating a (2S, 3R)-β-hydroxy-p-bromophenylalanine residue. Assembly was achieved through the initial synthesis of a cyclic depsipeptide and a linear peptide thioester fragment by solid-phase peptide synthesis, followed by fusion of the two fragments through a native chemical ligation-oxidation protocol. Extensive spectroscopic analysis showed structural differences to the isolated natural product, suggesting that a diastereoisomer of microspinosamide had been synthesised. This work lays the foundation for the future synthesis of the correct diastereoisomer.
- Santhakumar, Gajan,Payne, Richard J.
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- ANTIMICROBIAL COMPOUNDS AND METHODS
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The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
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- Synthesis and evaluation of photo-activatable β-diarylsydnone-L-alanines for fluorogenic photo-click cyclization of peptides
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Herein, we design and synthesize a series of photoactivatable β-diarylsydnone-l-alanines (DASAs), which have excellent photo-reactivity with high fluorescence turn-on toward alkenes in a biocompatible environment. The environmental sensing properties of t
- Yao, Zhuojun,Wu, Xueting,Zhang, Xiaocui,Xiong, Qin,Jiang, Shichao,Yu, Zhipeng
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supporting information
p. 6777 - 6781
(2019/07/22)
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- INTEGRIN ANTAGONISTS
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The present disclosure provides therapeutic agents including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such therapeutic agents. Methods of using the therapeutic agents are also provided.
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Page/Page column 70
(2018/05/24)
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- Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains
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As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki= 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki= 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki= 8.45 μM), which was the same as positive control Gossypol (Ki= 7.54 μM).
- Wan, Yichao,Liu, Tingting,Li, Xiaoxian,Chen, Chen,Fang, Hao
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p. 138 - 152
(2016/12/22)
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- PEPTIDYL NITRIL COMPOUNDS AS DIPEPTIDYL PEPTIDASE I INHIBITORS
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The invention relates to compounds of Formula (I) and its use as a selective dipeptidyl peptidase I inhibitor, as well as pharmaceutical compositions comprising said compounds, and methods of treatment involving said compounds.
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- N-SUBSTITUTED 3,3'-(BIPHENYL-4,4'-DIYL)BIS-2-AMINOPROPANENITRILES AS DPPI INHIBITORS
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The invention relates to a compound of Formula (I) and its use as a selective dipeptidyl peptidase I inhibitor, as well as pharmaceutical compositions comprising said compound, and methods of treatment involving said compounds.
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Page/Page column 42
(2015/03/28)
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- PEPTIDYL NITRILCOMPOUNDS AS PEPTIDASE INHIBITORS
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The invention relates to compounds of Formula (II) and their use in theraphy as peptidase inhibitors.
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- Negishi cross-coupling reactions of α-amino acid-derived organozinc reagents and aromatic bromides
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The Negishi cross-coupling reaction of organozinc iodides derived from α-amino acids with aromatic bromides to give substituted phenylalanine derivatives is described, using either Pd(OAc)2 or Pd2(dba)3 in combination with P(o-Tol)3 as catalyst in DMF at 50 °C. Similar results are obtained using Pd[PtBu3]2 as catalyst. The difference in reactivity displayed between aryl iodides and bromides (ArI>ArBr) has been utilised in a short synthesis of an unsymmetrical, orthogonally protected para-phenylene bis-alanine derivative.
- Oswald, Claire L.,Carrillo-Márquez, Tomás,Caggiano, Lorenzo,Jackson, Richard F.W.
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p. 681 - 687
(2008/09/16)
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- CYCLIC PEPTIDE ANTITUMOR AGENTS
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Cyclic peptide compounds and derivatives thereof having antitumor activity as shown by treatment of human melanoma, pancreatic, breast, prostate cancer cells.
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Page/Page column 2; 13-14; 17; sheet 3
(2010/02/11)
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- Solid-phase, Pd-catalyzed silicon-aryl carbon bond formation. Synthesis of sansalvamide A peptide.
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A palladium-catalyzed silicon-aryl carbon bond formation on solid-phase is reported. A phenylalanine silane resin was prepared directly from protected iodo-substituted phenylalanine with butyl diethylsilane polystyrene in one step. A rapid and high-yield solid-phase synthesis of sansalvamide A peptide was achieved from the phenylalanine silane resin. [reaction: see text]
- Gu, Wenxin,Liu S, Shouxin,Silverman, Richard B
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p. 4171 - 4174
(2007/10/03)
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- Rapid, high-yield, solid-phase synthesis of the antitumor antibiotic sansalvamide a using a side-chain-tethered phenylalanine building block
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(matrix presented) A 10-step solid-phase synthesis of the cytotoxic depsipeptide sansalvamide A (1) has been accomplished in an overall yield of 67% with >95% purity employing polymer-bound phenylalanine building block 2. Both the N- and C-termini of 2 are extended followed by on-resin head-to-tail macrocyclization of the linear peptide in a high yield. This should be a general stategy for the synthesis of diverse libraries of cyclic peptides and depsipeptides that contain exclusively phenylalanine and other hydrophobic side chains.
- Lee, Younghee,Silverman, Richard B.
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p. 3743 - 3746
(2007/10/03)
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