Highly Diastereoselective α-Hydroxylation of Fox Chiral Auxiliary-Based Amide Enolates with Molecular Oxygen

Lubin, Hodney; Tessier, Arnaud; Chaume, Grégory; Pytkowicz, Julien; Brigaud, Thierry

doi:10.1021/ol100211s

Cited by 50 publications

(22 citation statements)

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“…A Mukaiyama aldol reaction of aldehyde 16 , derived from d ‐phenylalanine, with silyl ketene acetal 15 in the presence of SnCl 4 (1.1 eq.) provided the corresponding adducts 22 as a 1:1 mixture of diastereomers (Scheme ).…”

Section: Figurementioning

confidence: 99%

A Total Synthesis of Prunustatin A

et al. 2015

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At otal synthesis of prunustatin A, aG RP78 molecular chaperone down-regulator,h as been achieved. The key step in the synthesis is an intramolecular transesterification of the b-keto ester alcohol intermediate to construct the 15-membered tetralactone core of the natural product.Microbial species have the capability to produce aw ide variety of bioactive compounds with previously unknown structures and variousb iological activities. Prunustatin A( 1,F igure 1), a1 5-memberedt etralactone antibiotic with a3 -formamidosalicylic moiety first isolatedi n2 005 by Shin-ya and co-workers from as train of Streptomycesv iolaceoniger 4521-SVS3, showed inhibitory activity against GRP78 expression inducedb y2 -deoxyglucose stimulationi nH T1080 cells.[1] Subsequents tudies established that the tetralactone moiety is made up of four subunits,( 4 S)-2,2-dimethyl-4-hydroxy-3-oxo-5-phenylpentanoic acid, (S)-lactic acid, l-threonine, and (2S,3S)-2-hydroxy-3-methylpentanoic acid, as shown in Figure 1.[2] Prunustatin A( 1)i s similar in structure to SW-163A (2) [3] and neoantimycin (3). [4] neoantimycin (3)i sarare and unusualr ing-extended member of the antimycin class. The recent discoveryo f1 as as elective GRP78 molecular chaperone down-regulator,w hichc ould lead to the development of new approaches towards treating cancer,h ighlights the potential of this class as research probes.Antimycin A 3 ,o ne of the first knowna nd most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc 1 complex. Since UK-2A, an antimycin-class antibiotic, was first isolatedi n1 996 from as oil sample collecteda to ur campus by Shibata, Ta niguchi and co-workers, [5] we have been attempting to establish the structure-activity relationshipsa mong antimycin A 3 and UK-2A (Figure 2).[6] As an extension of our research, we have been engaged in studies towardt he synthesis and biological evaluation of 1.Herein, we report atotal synthesis of prunustatin A( 1).Our initial access to construct the tetralactone core of 1 was based on an intramolecular Mitsunobu reaction of 4 as previously reported (Scheme 1), [7] where we have developedt he CÀ Cb ond formation reactionb etween C1 and C11v ia Reformatsky reaction. However,a ll attempts at cyclizationsb etween O2 and C2 via intramolecular Mitsunobu reaction and other lactonization procedures resulted in the formation of undesired five-membered lactones.T his would be caused by the gem-dimethylg roups at C11.Recently,t he first total synthesis of 1 was reported, [8] where cyclized point was selected at O4 and C5 by conformational Scheme1.Our initial access to construct the tetralactone core of 1.Boc = tert-butyloxycarbonyl.[ analysisa nd molecular dynamics. With these results in mind, we embarkedo nanew synthetic strategy towards 1 that involved cyclization via transesterification of b-keto ester 8 followed by introduction of the gem-dimethyl groups at C11 (Scheme2). Conceptually,r ing-closure precursor 8 would be prepared by condensat...

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Section: Figurementioning

confidence: 99%

A Total Synthesis of Prunustatin A

et al. 2015

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“…Based on the correlation of the optical rotation value with the literature [observed [α] D +80.5 (c 0.8 in EtOH), reported [α] D +72.5 (c 0.8 in EtOH)], an R configuration was unambiguously assigned. 8 The chiral auxiliary was recovered in 88% yield after the hydrolysis. A plausible mechanism for the stereoselectivity in glycolate alkylation is proposed in fig.…”

Section: Resultsmentioning

confidence: 99%

A highly efficient and enantioselective synthesis of EEHP and EMHP: intermediates of PPAR agonists

Gangar

Harikrishnan

Goyal

et al. 2016

Tetrahedron Letters

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“…Initially, Michael addition of 2-oxindole to enone affords the Michael adduct 3 . Under basic conditions, the reaction of 3 with O 2 generates peroxide A . , Intramolecular attacks of peroxide anion on the amide group produce the dioxetane intermediate B , which undergoes dissociation to generate C . Decarboxylation of C formed the product 4 .…”

Section: Resultsmentioning

confidence: 99%

2-Oxindole Acts as a Synthon of 2-Aminobenzoyl Anion in the K₂CO₃-Catalyzed Reaction with Enones: Preparation of 1,4-Diketones Bearing an Amino Group and Their Further Transformations

et al. 2015

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Highly Diastereoselective α-Hydroxylation of Fox Chiral Auxiliary-Based Amide Enolates with Molecular Oxygen

Cited by 50 publications

References 47 publications

A Total Synthesis of Prunustatin A

A Total Synthesis of Prunustatin A

A highly efficient and enantioselective synthesis of EEHP and EMHP: intermediates of PPAR agonists

2-Oxindole Acts as a Synthon of 2-Aminobenzoyl Anion in the K₂CO₃-Catalyzed Reaction with Enones: Preparation of 1,4-Diketones Bearing an Amino Group and Their Further Transformations

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Highly Diastereoselective α-Hydroxylation of Fox Chiral Auxiliary-Based Amide Enolates with Molecular Oxygen

Cited by 50 publications

References 47 publications

A Total Synthesis of Prunustatin A

A Total Synthesis of Prunustatin A

A highly efficient and enantioselective synthesis of EEHP and EMHP: intermediates of PPAR agonists

2-Oxindole Acts as a Synthon of 2-Aminobenzoyl Anion in the K2CO3-Catalyzed Reaction with Enones: Preparation of 1,4-Diketones Bearing an Amino Group and Their Further Transformations

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2-Oxindole Acts as a Synthon of 2-Aminobenzoyl Anion in the K₂CO₃-Catalyzed Reaction with Enones: Preparation of 1,4-Diketones Bearing an Amino Group and Their Further Transformations