- Total Synthesis of Proteasome Inhibitor (-)-Omuralide through Asymmetric Ketene [2 + 2]-Cycloaddition
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The total synthesis of (-)-omuralide, a potent specific proteasome inhibitor, has been achieved through an unprecedented route. The C3 and C4 chiral centers of the natural product have been selectively installed by an asymmetric [2 + 2]-cycloaddition betw
- Rullière, Pauline,Cannillo, Alexandre,Grisel, Julien,Cividino, Pascale,Carret, Sébastien,Poisson, Jean-Fran?ois
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p. 4558 - 4561
(2018/08/09)
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- Application of Two Direct C(sp3)-H Functionalizations for Total Synthesis of (+)-Lactacystin
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(Figure Presented). Herein, we report a new synthetic route from (S)-pyroglutaminol to (+)-lactacystin, a potent inhibitor of the 20S proteasome. The photoinduced intermolecular C(sp3)-H alkynylation and intramolecular C(sp3)-H acylation chemo- and stereoselectively constructed the tetra- and trisubstituted carbon centers, respectively. The obtained bicycle was transformed into the target compound in a concise manner. The present total synthesis demonstrates the power of the direct C(sp3)-H functionalizations for the assembly of multiple functionalized structures of natural products.
- Yoshioka, Shun,Nagatomo, Masanori,Inoue, Masayuki
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- Stereospecific total syntheses of proteasome inhibitors omuralide and lactacystin
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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
- Gu, Wenxin,Silverman, Richard B.
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p. 8287 - 8293
(2012/04/10)
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- Enantioselective total syntheses of (-)-clasto-lactacystin β-lactone and 7-epi-(-)-clasto-lactacystin β-lactone
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An alkylidene carbene 1,5-CH insertion has been used as a key step in an efficient enantioselective total synthesis of (-)-clasto-lactacystin β-lactone, and its C7-epimer. An additional noteworthy feature of the synthesis is the use of a novel oxidative deprotection procedure, utilizing DMDO, for the conversion of a late-stage benzylidene acetal into a primary alcohol and a secondary benzoate ester. The Royal Society of Chemistry 2006.
- Hayes, Christopher J.,Sherlock, Alexandra E.,Selby, Matthew D.
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p. 193 - 195
(2007/10/03)
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- Catalytic asymmetric total synthesis of (+)-lactacystin
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Total synthesis of (+)-lactacystin, a potent and selective proteasome inhibitor, was accomplished using a catalytic enantioselective Strecker reaction of a ketoimine as the initial key step. An enone-derived N-phosphinoyl ketoimine 7 was selected as a sta
- Fukuda, Nobuhisa,Sasaki, Kazuki,Sastry,Kanai, Motomu,Shibasaki, Masakatsu
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p. 1220 - 1225
(2007/10/03)
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- A concise route to (+)-lactacystin
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A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3- dioxan-5-ylcarbamate, e
- Ooi, Hidenori,Ishibashi, Norihisa,Iwabuchi, Yoshiharu,Ishihara, Jun,Hatakeyama, Susumi
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p. 7765 - 7768
(2007/10/03)
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- Total synthesis of (+)-lactacystin
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A double stereodifferentiating crotylation between aldehyde 1 and silane (S)-2 to afford homoallylic alcohol 3 is the key diastereoselective step (anti:syn > 30:1) in an efficient asymmetric synthesis of (+)-lactacystin. This compound is a metabolite isol
- Panek, James S.,Masse, Craig E.
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p. 1093 - 1095
(2007/10/03)
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- A novel and efficient synthesis of a highly active analogue of clasto-lactacystin β-lactone
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Herein, we describe a new convergent synthesis of a more potent analogue of clasto-lactacystin β-lactone (2), PS-519 compound 4, which is currently in preclinical development for the treatment of ischemia-reperfusion injury in stroke and myocardial infarction. The synthetic strategy relies on building two intermediates (an oxazoline and an aldehyde) which are joined through a doubly diastereoselective aldol reaction, setting up the requisite unichiral centers in the final product (4). The facial selectivity and ultimate stereocontrol are achieved by employing a trivalent aluminum Lewis acid, Me2AlCl, in a chelation-induced reaction which yields a single aldol adduct. The efficiency of the synthetic approach has allowed for the preparation of multigram quantities of clinical grade material, which will support Phase I studies.
- Soucy, Francois,Grenier, Louis,Behnke, Mark L.,Destree, Antonia T.,McCormack, Teresa A.,Adams, Julian,Plamondon, Louis
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p. 9967 - 9976
(2007/10/03)
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- A new magnesium-catalyzed doubly diastereoselective anti-aldol reaction leads to a highly efficient process for the total synthesis of lactacystin in quantity
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A new process is described for metal-catalyzed doubly diastereoselective Mukaiyama aldol coupling of a chiral tertiary α-amino aldehyde and an achiral silyl enol ether to form selectively an anti-aldol product. The metal requirement is strict, since of se
- Corey,Li, Weidong,Reichard, Gregory A.
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p. 2330 - 2336
(2007/10/03)
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- Stereoselective total synthesis of (+)-lactacystin from D-glucose
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The chiral and stereoselective synthesis of (+)-lactacystin 1, the first non-protein neurotrophic factor having an α,α-disubstituted α- amino acid structure, is described. The highly functionalized γ- lactam portion possessing a tetra-substituted carbon w
- Chida, Noritaka,Takeoka, Jun,Ando, Kohji,Tsutsumi, Noriko,Ogawa, Seiichiro
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p. 16287 - 16298
(2007/10/03)
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- Total synthesis of (+)-lactacystin
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A total synthesis of the novel neurotrophic agent (+)-lactacystin (1) has been achieved in 11 steps and 14% overall yield from (2R,3S)-3-hydroxyleucine [(+)-16]. The construction and bioassay of several active analogs are also described. A new asymmetric approach furnished the four stereoisomers of 3-hydroxyleucine, as required starting materials in high overall yield and enantiomeric purity.
- Nagamitsu, Tohru,Sunazuka, Toshiaki,Tanaka, Haruo,Omura, Satoshi,Sprengeler, Paul A.,Smith III, Amos B.
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p. 3584 - 3590
(2007/10/03)
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- Total Synthesis of (+)-Lactacystin from D-Glucose
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The chiral and stereoselective synthesis of (+)-lactacystin 1, the first non-protein neurotrophic factor, is described; the γ-lactam portion possessing a quaternary carbon in 1 was constructed stereoselectively from D-glucose using the allylic trichloroac
- Chida, Noritaka,Takeoka, Jun,Tsutsumi, Noriko,Ogawa, Seiichiro
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p. 793 - 794
(2007/10/02)
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- STUDIES ON THE TOTAL SYNTHESIS OF LACTACYCLIN. AN IMPROVED ALDOL COUPLING REACTION AND A β-LACTONE INTERMEDIATE IN THIOL ESTER FORMATION
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The recently developed total synthesis of lactacystin (1) has been improved by using the zirconium enolate derived from (R)- or (S)-2-silyloxy-1,2,2-triphenylpropionate which lead stereospecifically to either (6S,7R) or (6R,7S) lactacystin, respectively.T
- Corey, E. J.,Reichard, Gregory, A.,Kania, Robert
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p. 6977 - 6980
(2007/10/02)
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