437742-34-2Relevant articles and documents
A Total Synthesis of Salinosporamide A
Marx, Léo B.,Burton, Jonathan W.
, p. 6747 - 6754 (2018)
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.
Stereoselective enzymatic reduction of keto-salinosporamide to (-)-salinosporamide A (NPI-0052)
Manam, Rama Rao,Macherla, Venkat R.,Potts, Barbara C.M.
, p. 2537 - 2540 (2007)
Salinosporamide A (NPI-0052, 1), a highly potent 20S proteasome inhibitor, has been prepared from its ketone precursor (2) by asymmetric enzymatic reduction. The yields are quantitative with complete stereoselective conversion to the desired product, with no evidence for the undesired diastereomer. This process should lead to new synthetic strategies for the total synthesis of 1.
Preparation method and application of Marizomib key intermediate
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, (2020/07/02)
The invention belongs to the field of chemical synthesis, particularly relates to a preparation method and application of a Marizomib key intermediate, and particularly relates to a preparation methodof a Marizomib key intermediate. Natural L-serine is selected as an initial raw material, and an obtained serine fragment protected by a functional group is connected with a 1, 3-dicarbonyl cyclopropyl compound so that the Marizomib key intermediate (a skeleton structure) is prepared, and the preparation method is high in preparation efficiency and yield, safer and more environmentally friendly.Then, the prepared Marizomib key intermediate is used for producing Marizomib, and the Marizomib is obtained through intramolecular cyclization reaction and group modification, protective group removal and structural modification in sequence. Besides, the low-toxicity solvent is used in the whole synthesis process, reagents with high toxicity and difficult preparation are avoided, the solvent consumption is low, the target product recovery rate is high and the stability is good.
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.
Bioinspired total synthesis and human proteasome inhibitory activity of (-)-salinosporamide A, (-)-homosalinosporamide A, and derivatives obtained via organonucleophile promoted bis-cyclizations
Nguyen, Henry,Ma, Gil,Gladysheva, Tatiana,Fremgen, Trisha,Romo, Daniel
experimental part, p. 2 - 12 (2011/03/23)
A full account of concise, enantioselective syntheses of the anticancer agent (-)-salinosporamide A and derivatives, including (-)-homosalinosporamide, that was inspired by biosynthetic considerations is described. The brevity of the synthetic strategy stems from a key bis-cyclization of a β-keto tertiary amide, which retains optical purity enabled by A1,3-strain rendering slow epimerization relative to the rate of bis-cyclization. Optimization studies of the key bis-cyclization, enabled through byproduct isolation and characterization, are described that ultimately allowed for a gram scale synthesis of a versatile bicyclic core structure with a high degree of stereoretention. An optimized procedure for zincate generation by the method of Knochel, generally useful for the synthesis of salino A derivatives, led to dramatic improvements in side-chain attachment and a novel diastereomer of salino A. The versatility of the described strategy is demonstrated by the synthesis of designed derivatives including (-)-homosalinosporamide A. Inhibition of the human 20S and 26S proteasome by these derivatives using an enzymatic assay are also reported. The described total synthesis of salino A raises interesting questions regarding how biosynthetic enzymes leading to the salinosporamides proceeding via optically active β-keto secondary amides, are able to maintain the stereochemical integrity at the labile C2 stereocenter or if a dynamic kinetic resolution is operative.
Total synthesis of (-)-salinosporamide A
Satoh, Nobuhiro,Yokoshima, Satoshi,Fukuyama, Tohru
supporting information; experimental part, 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.
Total synthesis of (-)-salinosporamide A
Kaiya, Yuji,Hasegawa, Jun-Ichi,Momose, Takayuki,Sato, Takaaki,Chida, Noritaka
experimental part, 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
An enantio-and diastereocontrolled synthesis of (-)-salinosporamide A
Sato, Yosuke,Fukuda, Hayato,Tomizawa, Masaki,Masaki, Tomohito,Shibuya, Masatoshi,Kanoh, Naoki,Iwabuchi, Yoshiharu
, 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.
Total synthesis of salinosporamide A
Fukuda, Takeo,Sugiyama, Kouhei,Arima, Shiho,Harigaya, Yoshihiro,Nagamitsu, Tohru,Omura, Satoshi
supporting information; experimental part, p. 4239 - 4242 (2009/06/06)
(Chemical Equation Presented) The total synthesis of salinosporamide A has been achieved through enzymatic desymmetrization, diastereoselective aldol reaction, intramolecular aldol reaction, and intermolecular Reformatsky-type reaction followed by 1,4-reduction as key reactions.
A METHOD OF USING PROTEASOME INHIBITORS IN COMBINATION WITH HISTONE DEACETYLASE INHIBITORS TO TREAT CANCER
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Page/Page column 105, (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.
