Enantiodivergent Preparation of Chiral 2,5-Cyclohexadienone Synthons

Takano, Seiichi; Higashi, Youichirou; Kamikubo, Takashi; Moriya, M.; Ogasawara, Kunio

doi:10.1055/s-1993-25973

Cited by 56 publications

(28 citation statements)

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“…Through their research this compound is now readily available in both enantiomeric forms. 5–7 Ogasawara, Takano, and coworkers, as well as other research groups, have shown that the versatile building block 2 can be transformed into an extraordinary variety of structures in just a few steps, one of these being an obligate high-temperature retro-Diels–Alder reaction that expels cyclopentadiene. 8 …”

Section: Retrosynthetic Analysismentioning

confidence: 99%

A practical, convergent route to the key precursor to the tetracycline antibiotics

Kummer

Dion

et al. 2011

Chem. Sci.

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Here we describe a 5-step sequence to prepare the AB enone 1, the key precursor to fully synthetic tetracyclines, that begins with a diastereoselective Michael–Claisen coupling of two simple starting materials, a cyclohexenone (compound 2 or, in a refinement, a substituted variant, vide infra) and the isoxazole ester 3. This advance defines an 8-step linear sequence to 6-deoxytetracycline antibiotics from three components of similar complexity (cyclohexenone 2, isoxazole ester 3, and structurally diverse D-ring precursors) in which sequential diastereoselective Michael–Claisen cyclization reactions form the A- and C-rings, respectively, of the linearly fused ABCD tetracycline skeleton. In addition to providing a readily scalable, practical route to fully synthetic tetracyclines of broad structural diversity, the sequence reported comprises a series of non-obvious stereoselective transformations, including a novel means for C12a hydroxylation.

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Section: Retrosynthetic Analysismentioning

confidence: 99%

A practical, convergent route to the key precursor to the tetracycline antibiotics

Kummer

Dion

et al. 2011

Chem. Sci.

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“…4) to construct a 10-membered lactone moiety, and they started from the known endo-tricyclic Diels-Alder adduct 58 67) of cyclopentadiene and pbenzoquinone. Asymmetric centers were introduced by lipase-mediated enzymatic desymmetrization 68,69) of meso-diol, 70,71) which was obtained by reduction of 58. After oxidation to cyclohexanone 59, zinc-mediated Barbier-type allylation and subsequent oxy-Cope rearrangement 72) provided the allylated product as a single diastereomer.…”

Section: Synthetic Approaches To Sch 642305mentioning

confidence: 99%

Synthetic Studies of Natural 10-Membered Lactones, Mueggelone, Microcarpalide, and Sch 642305, Which Have Interesting Bioactivities

Ishigami

2009

Bioscience, Biotechnology, and Biochemistry

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A number of 10-membered lactones have been isolated as secondary metabolites, and many of them have interesting and potent activities. Because of synthetic and biological interests, many synthetic studies of these compounds have been made. This review summarizes synthetic approaches to three natural 10-membered lactones, mueggelone, microcarpalide, and Sch 642305. Mueggelone is an inhibitor of fish development, microcarpalide is a microfilament disrupting agent, and Sch 642305 is an inhibitor of bacterial DNA primase.

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“…2 Asymmetric approaches to these compounds have included whole cell oxidations of arenes to cis -arene diols, 3 Baker’s yeast reduction of β-ketoesters, 4 stoichiometric 5 and catalytic 6 asymmetric Diels-Alder reactions, asymmetric epoxidation, 2a,7 use of a sulfoxide chiral auxiliary, 8 enzymatic resolution of racemic 9 or meso diols, 10 from quinic acid, 11 and by catalytic alkene isomerization of a meso bis -silyl ether. 12 …”

Section: Introductionmentioning

confidence: 99%

“…Thus, while racemic 1a has been prepared in 4 steps from benzoquinone, 16 the reported asymmetric synthesis of the corresponding silyl ether 1i required eight steps from benzoquinone, a high enzyme loading for the desymmetrization step (lipase PS-D, 1 eq by weight), and a long reaction time (16 days). 17,18 …”

Section: Introductionmentioning

confidence: 99%

Efficient, scalable asymmetric synthesis of an epoxy quinol via Noyori desymmetrization of a meso diketone

Clay

Rosenberg

McIntosh

2011

Tetrahedron: Asymmetry

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Epoxy quinol 1a was prepared on a multi-gram scale by Noyori transfer hydrogenative desymmetrization of the readily available meso epoxy diketone 4. Although the intrinsic enantioselectivity for the desymmetrization was modest (82:18 er at 4% conversion), a highly enantiopure product (99.6:0.4 er) could be obtained in one operation in 44% yield via kinetic resolution of the minor enantiomer with long reaction times (48 h), or in 73% yield by combination with an enzymatic resolution of a 93:7 er mixture.

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Enantiodivergent Preparation of Chiral 2,5-Cyclohexadienone Synthons

Cited by 56 publications

References 0 publications

A practical, convergent route to the key precursor to the tetracycline antibiotics

A practical, convergent route to the key precursor to the tetracycline antibiotics

Synthetic Studies of Natural 10-Membered Lactones, Mueggelone, Microcarpalide, and Sch 642305, Which Have Interesting Bioactivities

Efficient, scalable asymmetric synthesis of an epoxy quinol via Noyori desymmetrization of a meso diketone

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