99776-34-8Relevant academic research and scientific papers
Rational hopping of a peptidic scaffold into non-peptidic scaffolds: Structurally novel potent proteasome inhibitors derived from a natural product, belactosin A
Kawamura, Shuhei,Unno, Yuka,Hirokawa, Takatsugu,Asai, Akira,Arisawa, Mitsuhiro,Shuto, Satoshi
supporting information, p. 2445 - 2447 (2014/03/21)
Rational scaffold hopping of a natural product belactosin A derivative was successfully achieved based on the pharmacophore model constructed. The peptidic scaffold was replaced by significantly simplified non-peptidic scaffolds, by which weak belactosin A (IC50 = 1440 nM) was converted into highly potent non-peptidic inhibitors (IC50 = 26-393 nM).
Structurally novel highly potent proteasome inhibitors created by the structure-based hybridization of nonpeptidic belactosin derivatives and peptide boronates
Kawamura, Shuhei,Unno, Yuka,Asai, Akira,Arisawa, Mitsuhiro,Shuto, Satoshi
supporting information, p. 2726 - 2735 (2014/04/17)
We previously developed highly potent proteasome inhibitor 1 (IC 50 = 5.7 nM) and its nonpeptide derivative 2 (IC50 = 29 nM) by systematic structure-activity relationship studies of the peptidic natural product belactosin A and subsequent rational topology-based scaffold hopping, respectively. Their cell growth inhibitory activities, however, were only moderate (IC50 = 1.8 μM (1) and >10 μM (2)). We therefore planned to replace the unstable β-lactone warhead with a more stable boronic acid warhead. Importantly, belactosin derivatives bind mainly to the proteasome binding site, which is different from that occupied by known peptide boronate proteasome inhibitors such as bortezomib, suggesting that their hybridization might lead to the development of novel potent inhibitors. Here we describe design, synthesis, and biological activities of the newly developed potent hybrid proteasome inhibitors. Interestingly, these hybrids, unlike bortezomib, were highly selective for proteasomes and have long residence times despite having the same boronic acid warhead.
A cyclic acetal tethered intramolecular diels-alder cycloaddition. studies directed toward a total synthesis of (±)-fusidilactone C
Ghosh, Sunil K.,Wei, Yonggang,Gerasyuto, Aleksey I.,Feltenberger, John B.,Wang, Jiashi,Hsung, Richard P.
experimental part, p. 1379 - 1409 (2011/05/14)
Efforts toward a synthesis of (±)-fusidilactone C is described here featuring a novel cyclic acetal tethered intramolecular Diels-Alder strategy. This unique and facile IMDA turned out to be highly endo-selective [endo-I and endo-II], as assessed from our mechanistic analyses. When using protic solvents or Lewis acids, the endo-I selectivity was greatly enhanced. Thus, it proved to be a real challenge to circumvent this excellent stereochemical outcome, which is undesired for the total synthesis, as an exo-II selectivity is desired. Progress was made to use the endo-II cycloadduct and to access the desired trans-2-oxadecalin motif in (±)-fusidilactone C. The Japan Institute of Heterocyclic Chemistry.
Stereoselective ketal-tethered intramolecular Diels-Alder cycloadditions. An approach to the 2-oxadecalin spiroketal core of antifungal agent fusidilactone C
Wang, Jiashi,Hsung, Richard P.,Ghosh, Sunil K.
, p. 1939 - 1942 (2007/10/03)
Equation presented. An approach toward the 2-oxadecalin spiroketal core of fusidilactone C via a rare ketal-tethered intramolecular Diels-Alder cycloaddition is described here. This intramolecular Diels-Alder cycloaddition is highly endo-selective and ove
Acetonyltriphenylphosphonium bromide in organic synthesis: A useful catalyst in the cyclotrimerization of aldehydes
Hon, Yung-Son,Lee, Chia-Fu
, p. 6181 - 6188 (2007/10/03)
Acetonyltriphenylphosphonium bromide (ATPB) is a useful catalyst for the cyclotrimerization of the aliphatic aldehydes under solvent-free condition. The aldehydes tethered with a variety of functionality such as olefin, ether, ester, bromide, azide and diester could also be cyclotrimerized under the catalysis of ATPB.
C-Nucleoside Studies. Part 21. Synthesis of Some Hydroxyalkylated Pyrrolo- and Thieno-pyrimidines Related to Known Antiviral Acyclonucleosides
Buchanan, J. Grant,Craven, David A.,Wightman, Richard H.,Harnden, Michael R.
, p. 195 - 202 (2007/10/02)
Treatment of (S)-4,5-isopropylidenedioxypentanonitrile 17 with ethyl formate and sodium hydride gave a hydroxymethylene derivative which interacted with aminoacetonitrile to give 3-cyanomethyleneamino-2-acrylonitrile 19; this was elaborated via 3-amino-2-cyano-4-pyrrol 22 into 4-amino-7-pyrrolopyrimidine 9.Treatment of the hydroxymethylene derivative of 17 with methanesulphonyl chloride, followed by acetylthioacetonitrile and sodium carbonate in ethanol gave 3-amino-2-cyano-4-thiophene 25, convertible in two steps into 4-amino-7-thienopyrimidine 10. Similar chemistry was employed for the conversion of 5,6-isopropylidenedioxyhexanonitril 30 into the higher homologues 4-amino-7-(3,4-dihydroxybutyl)pyrrolo- and thieno-(3,2-d)pyrimidine 11 and 12, and for the preparation of 4-amino-7-(4-hydroxy-3-hydroxymethylbutyl)pyrrolopyrimidine 13 from 6-benzyloxy-5-benzyloxymethylhexanonitrile 41.The hydroxyalkylated products 9-13 are C-nucleosides analogues of known antiviral agents, but did display antiviral activity.
