190080-34-3Relevant academic research and scientific papers
Total Synthesis of Zephycarinatines via Photocatalytic Reductive Radical ipso-Cyclization
Ichimura, Atsuhiko,Inuki, Shinsuke,Kawabe, Takaaki,Nakagawa, Kohei,Ohno, Hiroaki,Oishi, Shinya,Takeuchi, Haruka
, p. 21210 - 21215 (2020)
We report herein a nonbiomimetic strategy for the total synthesis of the plicamine-type alkaloids zephycarinatines C and D. The key feature of the synthesis is a stereoselective reductive radical ipso-cyclization using visible-light-mediated photoredox ca
Discovery of a Potent Thiazolidine Free Fatty Acid Receptor 2 Agonist with Favorable Pharmacokinetic Properties
Hansen, Anders H?jgaard,Sergeev, Eugenia,Bolognini, Daniele,Sprenger, Richard R.,Ekberg, Jeppe Hvidtfeldt,Ejsing, Christer S.,McKenzie, Christine J.,Rexen Ulven, Elisabeth,Milligan, Graeme,Ulven, Trond
supporting information, p. 9534 - 9550 (2018/10/24)
Free fatty acid receptor 2 (FFA2/GPR43) is a receptor for short-chain fatty acids reported to be involved in regulation of metabolism, appetite, fat accumulation, and inflammatory responses and is a potential target for treatment of various inflammatory and metabolic diseases. By bioisosteric replacement of the central pyrrolidine core of a previously disclosed FFA2 agonist with a synthetically more tractable thiazolidine, we were able to rapidly synthesize and screen analogues modified at both the 2- and 3-positions on the thiazolidine core. Herein, we report SAR exploration of thiazolidine FFA2 agonists and the identification of 31 (TUG-1375), a compound with significantly increased potency (7-fold in a cAMP assay) and reduced lipophilicity (50-fold reduced clogP) relative to the pyrrolidine lead structure. The compound has high solubility, high chemical, microsomal, and hepatocyte stability, and favorable pharmacokinetic properties and was confirmed to induce human neutrophil mobilization and to inhibit lipolysis in murine adipocytes.
Total Synthesis of Tambromycin by Combining Chemocatalytic and Biocatalytic C?H Functionalization
Zhang, Xiao,King-Smith, Emma,Renata, Hans
supporting information, p. 5037 - 5041 (2018/03/27)
A combination of genomic and metabolomic approaches recently resulted in the identification of a nonribosomal tetrapeptide tambromycin, which possesses promising antiproliferative activity and several unusual structural features, including a densely substituted indole, a methyloxazoline ring, and an unusual pyrrolidine-containing amino acid called tambroline. In this work, we identify a concise synthetic route to access tambromycin, which relies on the strategic use of biocatalytic and chemocatalytic C?H functionalization methods to prepare two key precursors to the natural product in an efficient and scalable manner. The success of our study highlights the benefits of applying the principles of biocatalytic retrosynthesis as well as C?H functionalization logic to the synthesis of complex molecular scaffolds.
Kinase-independent phosphoramidate S1P1receptor agonist benzyl ether derivatives
James, Edward,Pertusati, Fabrizio,Brancale, Andrea,McGuigan, Chris
, p. 1371 - 1378 (2017/03/08)
Previously published S1P receptor modulator benzyl ether derivatives have shown potential as being viable therapeutics for the treatment of neurodegenerative diseases, however, two of the most S1P1-selective compounds are reported as being poorly phosphorylated by kinases in vivo. Phosphoramidates of BED compounds (2a, 2b) were synthesised with the aim of producing kinase-independent S1P receptor modulators. Carboxypeptidase, human serum and cell lysate processing experiments were conducted. ProTide BED analogues were found to have an acceptable level of stability in acidic and basic conditions and in vitro metabolic processing experiments showed that they are processed to the desired pharmacologically active monophosphate. The research describes the development of an entirely novel family of therapeutic agents.
Remote stereocontrol in [3,3]-sigmatropic rearrangements: Application to the total synthesis of the immunosuppressant mycestericin G
Fairhurst, Nathan W. G.,Mahon, Mary F.,Munday, Rachel H.,Carbery, David R.
supporting information; experimental part, p. 756 - 759 (2012/03/26)
The Ireland - Claisen [3,3]-sigmatropic rearrangement has been used to access biologically important β,β′-dihydroxy α-amino acids. The rearrangement reported is highly stereoselective and offers excellent levels of remote stereocontrol. This strategy has been used to synthesize the natural immunosuppressant mycestericin G and ent-mycestericin G, allowing for a revision of absolute configuration of this natural product.
Stereospecific total syntheses of proteasome inhibitors omuralide and lactacystin
Gu, Wenxin,Silverman, Richard B.
scheme or table, p. 8287 - 8293 (2012/04/10)
Omuralide, a transformation product of the microbial metabolite lactacystin, was the first molecule discovered as a specific inhibitor of the proteasome and is unique in that it specifically inhibits the proteolytic activity of the 20S subunit of the prot
Novel Chiral Skeletons for Drug Discovery: Antibacterial Tetramic Acids
Holloway, Chloe A.,Matthews, Christopher J.,Jeong, Yong-Chul,Moloney, Mark G.,Roberts, Christine F.,Yaqoob, Muhammad
scheme or table, p. 229 - 235 (2012/05/20)
Modification of the ring nucleus of tetramic acids derived from serine gives chiral heterocyclic libraries that exhibit antibacterial activity, and correlation with various physicochemical parameters indicates that chiral tetramic acids may provide a potentially valuable non-aromatic skeleton for fragment-based drug discovery. Chiral tetramates are useful chiral fragments which may be used to generate libraries with antibacterial activity.
Diels-Alder cycloaddition of chiral nonracemic 2,5-diketopiperazine dienes
Morris, Erin N.,Nenninger, E. Katherine,Pike, Robert D.,Scheerer, Jonathan R.
supporting information; experimental part, p. 4430 - 4433 (2011/10/08)
Preparation of a chiral, nonracemic 2,5-diketopiperazine diene has enabled the investigation of intermolecular hetero-Diels-Alder cycloadditions. The diketopiperazine diene is reactive with both electron-rich and -deficient alkene substrates. Diastereofacial control in the cycloaddition is enforced with a removable aminal substituent. This study partly illuminates the regiochemical, stereoelectronic, and reactivity preferences of the diketopiperazine cycloaddition as well as provides a direct diastereoselective synthetic route to bicyclo[2.2.2]diazaoctane structures.
Concise formal synthesis of (-)-salinosporamide a (marizomib) using a regio- and stereoselective epoxidation and reductive oxirane ring-opening strategy
Ling, Taotao,Potts, Barbara C.,MacHerla, Venkat R.
supporting information; experimental part, p. 3882 - 3885 (2010/08/06)
Figure presented Expedient access to a highly functionalized 2-pyrrolidinone (8), the γ-lactam core of 20S proteasome inhibitor (-)-salinosporamide A (marizomib; NPI-0052; 1), using a regio- and stereoselective epoxide formation/reductive oxirane ring-ope
TOTAL SYNTHESIS OF SALINOSPORAMIDE A AND ANALOGS THEREOF
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Page/Page column 43, (2009/09/28)
The present application relates to certain compounds and to methods for the preparation of certain compounds that can be used in the fields of chemistry and medicine. Specifically, described herein are methods for the preparation of various compounds and intermediates, and the compounds and intermediates themselves. More specifically, described herein are methods for synthesizing Salinosporamide A and its analogs that includes forming a compound of formula (VIII).
