155975-72-7Relevant academic research and scientific papers
Utility of the ammonia-free birch reduction of electron-deficient pyrroles: Total synthesis of the 20S proteasome inhibitor, clasto-lactacystin β-lactone
Donohoe, Timothy J.,Sintim, Herman O.,Sisangia, Leena,Ace, Karl W.,Guyo, Paul M.,Cowley, Andrew,Harling, John D.
, p. 4227 - 4238 (2005)
A new synthesis of the 20S proteasome inhibitor clasto-lactacystin β-lactone is described. Our route to this important natural product involves the partial reduction of an electron deficient pyrrole as a key step. By judicious choice of enolate counterion, we were able to exert complete control over the stereoselectivity of the reduction/aldol reaction. Early attempts to complete the synthesis by using a C-4 methyl substituted pyrrole are described in full, together with our attempts to promote regioselective elimination of a tertiary alcohol. The lessons learnt from this first approach led us to develop another, and ultimately successful, route that introduced the C-4 methyl group at a late stage in the synthesis. Our successful route is then described and this contains several highly stereoselective steps including a cis-dihydroxylation and an enolate methylation. The final synthesis proceeds in just 13 steps and in 15% overall yield making it an extremely efficient route to this valuable compound.
An efficient synthesis of lactacystin β-lactone
Donohoe, Timothy J.,Sintim, Herman O.,Sisangia, Leena,Harling, John D.
, p. 2293 - 2296 (2004)
A key step in the synthesis of lactacystin β-lactone (3), an inhibitor of the 20 S proteasome, was the ammonia-free reductive aldol reaction of pyrrole 1 to form 2 with complete anti selectivity. This route to 3 takes just 13 steps (14% overall yield) and allows the late-stage stereoselective introduction of a methyl group at C4, which is crucial for the production of analogues. Boc = tert-butoxycarbonyl.
Total Synthesis of Proteasome Inhibitor (-)-Omuralide through Asymmetric Ketene [2 + 2]-Cycloaddition
Rullière, Pauline,Cannillo, Alexandre,Grisel, Julien,Cividino, Pascale,Carret, Sébastien,Poisson, Jean-Fran?ois
, p. 4558 - 4561 (2018/08/09)
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
Application of Two Direct C(sp3)-H Functionalizations for Total Synthesis of (+)-Lactacystin
Yoshioka, Shun,Nagatomo, Masanori,Inoue, Masayuki
, p. 90 - 93 (2015/07/28)
(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.
Stereospecific total syntheses of proteasome inhibitors omuralide and lactacystin
Gu, Wenxin,Silverman, Richard B.
, p. 8287 - 8293 (2012/04/10)
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
Enantioselective total syntheses of omuralide, 7-epi-omuralide, and (+)-lactacystin
Hayes, Christopher J.,Sherlock, Alexandra E.,Green, Martin P.,Wilson, Claire,Blake, Alexander J.,Selby, Matthew D.,Prodger, Jeremy C.
, p. 2041 - 2051 (2008/09/19)
(Chemical Equation Presented) An alkylidene carbene 1,5-CH insertion has been used as a key step in an enantioselective total syntheses of omuralide, its C7-epimer, and (+)-lactacystin. An additional noteworthy feature of the synthesis is the use of a nov
Stereogenic evolution of clasto-lactacystin β-lactone from L-serine
Yoon, Cheol H.,Flanigan, David L.,Yoo, Kyung S.,Jung, Kyung W.
, p. 37 - 39 (2007/10/03)
Reported herein is a novel synthesis of clasto-lactacystin β-lactone. The γ-lactam core was selectively prepared by an intramolecular C-H insertion to establish the stereocenter, C(6). The ensuing construction of the quaternary C(5) and carbinol C(9) cent
Enantioselective total syntheses of (-)-clasto-lactacystin β-lactone and 7-epi-(-)-clasto-lactacystin β-lactone
Hayes, Christopher J.,Sherlock, Alexandra E.,Selby, Matthew D.
, p. 193 - 195 (2007/10/03)
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.
SUBSTITUTED 2-PYRROLIDONE DERIVATIVES AS FUNGICIDES AND INSECTICIDES
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Page/Page column 109-110, (2010/02/15)
The use of a compound of formula (I) or a salt thereof, where the symbols have the meanings given in the description, for the control of phytopathogenic mircroorganisms of harmful animals.
Catalytic asymmetric total synthesis of (+)-lactacystin
Fukuda, Nobuhisa,Sasaki, Kazuki,Sastry,Kanai, Motomu,Shibasaki, Masakatsu
, p. 1220 - 1225 (2007/10/03)
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
