823229-54-5Relevant academic research and scientific papers
Total Synthesis of (?)-Salinosporamide A via a Late Stage C?H Insertion
Gholami, Hadi,Kulshrestha, Aman,Favor, Olivia K.,Staples, Richard J.,Borhan, Babak
, p. 10110 - 10113 (2019/04/25)
The synthesis of (?)-salinosporamide A, a proteasome inhibitor, is described. The synthesis highlights the assembly of a densely decorated pyrrolidinone core via an aza-Payne/hydroamination sequence. Central to the success of the synthesis is a late-stage C?H insertion reaction to functionalize a sterically encumbered secondary carbon. The latter functionalization leads to an enabling transformation where most of the prototypical strategies failed.
A Total Synthesis of Salinosporamide A
Marx, Léo B.,Burton, Jonathan W.
supporting information, p. 6747 - 6754 (2018/05/14)
Salinosporamide A is a β-lactone proteasome inhibitor currently in clinical trials for the treatment of multiple-myeloma. Herein we report a short synthesis of this small, highly functionalized, biologically important natural product that uses an oxidative radical cyclization as a key step and allows for the preparation of gram quantities of advanced synthetic intermediates.
Total synthesis of (-)-salinosporamide A
Kaiya, Yuji,Hasegawa, Jun-Ichi,Momose, Takayuki,Sato, Takaaki,Chida, Noritaka
, p. 209 - 219 (2011/10/03)
A detailed description of our second-generation total synthesis of salinosporamideA is presented. Three contiguous stereocenters in the γ-lactam structure seen in the natural product were established by stereoselective functionalization of a D-arabinose scaffold, including an Overman rearrangement to generate a highly congested tetrasubstituted carbon center. One of the definitive reactions in the synthesis was a Lewis acid mediated skeletal rearrangement of a pyranose structure, which enabled the practical conversion of the carbohydrate scaffold to the γ-lactam structure embedded in salinosporamideA. The use of a benzyl ester as a protective group for a sterically hindered carboxylic acid led to a one-pot global deprotection at the end of the synthesis. Rearrange your chemistry! The total synthesis of anticancer natural product salinosporamideA has been achieved through a unique skeletal rearrangement (see scheme). This reaction enabled the construction of the densely functionalized γ-lactam structure found in salinosporamideA through practical methodologies including an Overman rearrangement on a D-arabinose scaffold. Copyright
Total synthesis of (-)-salinosporamide A
Satoh, Nobuhiro,Yokoshima, Satoshi,Fukuyama, Tohru
, p. 3028 - 3031 (2011/08/06)
A concise and stereoselective total synthesis of (-)-salinosporamide A (1), a potent inhibitor of the 20S proteasome that is in clinical development as an anticancer drug candidate, has been accomplished in 14 steps with 19% overall yield from 4-pentenoic acid. Our synthesis features a stereoselective alkylation utilizing a chiral auxiliary, formation of a pyrrolidine unit, and oxidation of the pyrrolidine to a γ-lactam. To demonstrate the scalability of our synthesis, (-)-salinosporamide A has been synthesized on a gram scale.
An enantio-and diastereocontrolled synthesis of (-)-salinosporamide A
Sato, Yosuke,Fukuda, Hayato,Tomizawa, Masaki,Masaki, Tomohito,Shibuya, Masatoshi,Kanoh, Naoki,Iwabuchi, Yoshiharu
scheme or table, p. 2239 - 2246 (2011/04/15)
The enantio-and diastereocontrolled total synthesis of (-)-salinosporamide A, a potent 20S proteasome inhibitor, was accomplished through organocatalytic aldolization, diastereoselective Claisen condensation, a Rh-catalyzed Reformatsky reaction, and an AZADO-catalyzed oxidative β-lactonization reaction as the key reactions. The Japan Institute of Heterocyclic Chemistry.
PROTEASOME INHIBITORS
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Page/Page column 58-59, (2009/12/23)
Disclosed herein are compounds of Formula (I) that include a sulfonate ester, ester or ether group. Compounds of Formula (I) can be included in pharmaceutical compositions, and can be used to treating and/or ameliorating a disease or condition, such as ca
A METHOD OF USING PROTEASOME INHIBITORS IN COMBINATION WITH HISTONE DEACETYLASE INHIBITORS TO TREAT CANCER
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, (2008/12/04)
Disclosed are methods of treating cancer comprising administering to the animal, a therapeutically effective amount of proteasome inhibitors and one or more histone deacetylase inhibitor. The animal is a mammal, preferably a human or a rodent.
Entry to heterocycles based on indium-catalyzed Conia-ene reactions: Asymmetric synthesis of (-)-salinosporamide A
Takahashi, Keisuske,Midori, Michiko,Kawano, Kei,Ishihara, Jun,Hatakeyama, Susumi
supporting information; experimental part, p. 6244 - 6246 (2009/04/06)
Conica can: The In(OTf)3-catalyzed cyclization of nitrogen- and oxygen-tethered acetylenic malonic esters gives five- to seven-membered heterocycles in moderate to excellent yields (see scheme; Tf = trifluoromethanesulfonyl). The asymmetric synthesis of (-)-salinosporamide A illustrates the synthetic utility of the method. (Chemical Equation Presented).
Leaving groups prolong the duration of 20S proteasome inhibition and enhance the potency of salinosporamides
Manam, Rama Rao,McArthur, Katherine A.,Chao, Ta-Hsiang,Weiss, Jeffrey,Ali, Janid A.,Palombella, Vito J.,Groll, Michael,Lloyd, G. Kenneth,Palladino, Michael A.,Neuteboom, Saskia T. C.,Macherla, Venkat R.,Potts, Barbara C. M.
experimental part, p. 6711 - 6724 (2009/11/30)
Salinosporamide A (1 (NPI-0052)) is a potent, monochlorinated 20S proteasome inhibitor in clinical trials for the treatment of cancer. To elucidate the role of the chlorine leaving group (LG), we synthesized analogues with a range of LG potentials and det
METHODS OF USING [3.2.0] HETEROCYCLIC COMPOUNDS AND ANALOGS THEREOF FOR THE TREATMENT OF LUNG CANCER
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, (2008/06/13)
Disclosed are methods of treating lung cancer comprising administering to the animal, a therapeutically effective amount of a heterocyclic compound, alone or in combination with another therapeutic.
