Propellane as a conformational device for the stabilization of the β-lactone of salinosporamide A

Tetrahedron ◽  
2009 ◽  
Vol 65 (31) ◽  
pp. 5899-5903 ◽  
Author(s):  
Mitchell Vamos ◽  
Yoshihisa Kobayashi
Keyword(s):  
Salinosporamide A

scholarly journals Comparison of biochemical and biological effects of ML858 (salinosporamide A) and bortezomib

2006 ◽  
Vol 5 (12) ◽  
pp. 3052-3061 ◽  
Author(s):  
Mark J. Williamson ◽  
Jonathan L. Blank ◽  
Frank J. Bruzzese ◽  
Yueying Cao ◽  
J. Scott Daniels ◽  
...  
Keyword(s):  
Biological Effects ◽  
Salinosporamide A

scholarly journals Back Cover: Total Synthesis of (−)‐Salinosporamide A via a Late Stage C−H Insertion (Angew. Chem. Int. Ed. 30/2019)

2019 ◽  
Vol 58 (30) ◽  
pp. 10376-10376
Author(s):  
Hadi Gholami ◽  
Aman Kulshrestha ◽  
Olivia K. Favor ◽  
Richard J. Staples ◽  
Babak Borhan
Keyword(s):  
Total Synthesis ◽  
Late Stage ◽  
Back Cover ◽  
Salinosporamide A

scholarly journals Synthetic studies of salinosporamide A through the intramolecular hydroamidation of alkynes

2011 ◽  
Vol 696 (1) ◽  
pp. 42-45 ◽  
Author(s):  
Haruhi Kamisaki ◽  
Yusuke Kobayashi ◽  
Tetsutaro Kimachi ◽  
Yoshizumi Yasui ◽  
Yoshiji Takemoto
Keyword(s):  
Salinosporamide A ◽  
Synthetic Studies

scholarly journals Diastereoselective Synthesis of Fused Lactone-Pyrrolidinones; Application to a Formal Synthesis of (−)-Salinosporamide A

2014 ◽  
Vol 16 (16) ◽  
pp. 4078-4081 ◽  
Author(s):  
Angus W. J. Logan ◽  
Simon J. Sprague ◽  
Robert W. Foster ◽  
Léo B. Marx ◽  
Vincenzo Garzya ◽  
...  
Keyword(s):  
Diastereoselective Synthesis ◽  
Formal Synthesis ◽  
Salinosporamide A

Exploration and engineering of biosynthetic pathways in the marine actinomycete Salinispora tropica

2009 ◽  
Vol 81 (6) ◽  
pp. 1075-1084 ◽  
Author(s):  
Markus Nett ◽  
Bradley S. Moore
Keyword(s):  
Natural Products ◽  
Metabolic Pathways ◽  
Anticancer Agent ◽  
Complex Molecules ◽  
Dna Cleaving ◽  
Metabolic Plasticity ◽  
Salinosporamide A ◽  
Salinispora Tropica ◽  
Marine Actinomycete ◽  
Key Genes

In recent years, members of the marine actinomycete genus Salinispora have proven to be a precious source of structurally diverse secondary metabolites, including the potent anticancer agent salinosporamide A and the enediyne-derived sporolides. The tremendous potential of these marine-dwelling microbes for natural products biosynthesis, however, was not fully realized until sequencing of the Salinispora tropica genome revealed the presence of numerous orphan biosynthetic loci besides a plethora of rare metabolic pathways. This contribution summarizes the biochemical exploration of this prolific organism, highlighting studies in which genome-based information was exploited for the discovery of new enzymatic processes and the engineering of unnatural natural products. Inactivation of key genes within the salinosporamide pathway has expanded its inherent metabolic plasticity and enabled access to various salinosporamide derivatives by mutasynthesis. New insights into the biosynthesis of the sporolides allowed us to increase production titers of these structurally complex molecules, thereby providing the means to search for the DNA cleaving presporolide enediyne.

scholarly journals Coupled Biosynthesis of Volatiles and Salinosporamide A in Salinispora tropica

ChemBioChem ◽  
2016 ◽  
Vol 17 (20) ◽  
pp. 1978-1985 ◽  
Author(s):  
Ulrike Groenhagen ◽  
Ana Ligia Leandrini De Oliveira ◽  
Elisha Fielding ◽  
Bradley S. Moore ◽  
Stefan Schulz
Keyword(s):  
Salinosporamide A ◽  
Salinispora Tropica

Coupling of sterically hindered aldehyde with fluorinated synthons: Stereoselective synthesis of fluorinated analogues of salinosporamide A

2012 ◽  
Vol 136 ◽  
pp. 12-19 ◽  
Author(s):  
Zeng-Hao Chen ◽  
Bing-Lin Wang ◽  
Andrew J. Kale ◽  
Bradley S. Moore ◽  
Ruo-Wen Wang ◽  
...  
Keyword(s):  
Stereoselective Synthesis ◽  
Salinosporamide A ◽  
Sterically Hindered

scholarly journals (−)-Homosalinosporamide A and Its Mode of Proteasome Inhibition: An X-ray Crystallographic Study

Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 240 ◽  
Author(s):  
Michael Groll ◽  
Henry Nguyen ◽  
Sreekumar Vellalath ◽  
Daniel Romo
Keyword(s):  
Natural Product ◽  
Active Site ◽  
Late Stage ◽  
Enzyme Assay ◽  
Proteasome Inhibition ◽  
Fine Tuning ◽  
Synthetic Approach ◽  
X Ray ◽  
Salinosporamide A ◽  
Crystallographic Study

Upon acylation of the proteasome by the β-lactone inhibitor salinosporamide A (SalA), tetrahydrofuran formation occurs by intramolecular alkylation of the incipient alkoxide onto the choroethyl sidechain and irreversibly blocks the active site. Our previously described synthetic approach to SalA, utilizing a bioinspired, late-stage, aldol-β-lactonization strategy to construct the bicyclic β-lactone core, enabled synthesis of (–)-homosalinosporamide A (homoSalA). This homolog was targeted to determine whether an intramolecular tetrahydropyran is formed in a similar manner to SalA. Herein, we report the X-ray structure of the yeast 20S proteasome:homoSalA-complex which reveals that tetrahydropyran ring formation does not occur despite comparable potency at the chymotrypsin-like active site in a luminogenic enzyme assay. Thus, the natural product derivative homoSalA blocks the proteasome by a covalent reversible mode of action, opening the door for further fine-tuning of proteasome inhibition.

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