- Synthesis of tetrahydrofuran-based natural products and their carba analogs via stereoselective enzyme mediated Baeyer–Villiger oxidation
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In this work we present efficient formal syntheses of several biologically interesting natural products (showdomycin, goniofufurone, trans-kumausyne) and their novel carba analogs by applying different Baeyer–Villiger monooxygenases. This strategy provides access to tetrahydrofuran-based natural products, C-nucleosides and both antipodes of the corresponding carba analogs in high optical purities (up to >95% ee) starting from simple achiral and commercially available building blocks (tetrabromoacetone, furan and cyclopentadiene). The striking key features of this chemo-enzymatic approach are the introduction of four stereogenic centers in as few as three reaction steps within a desymmetrization approach and the short-cut of several reaction sequences by the implementation of a biocatalytic step.
- Rudroff, Florian,Bianchi, Dario A.,Moran-Ramallal, Roberto,Iqbal, Naseem,Dreier, Dominik,Mihovilovic, Marko D.
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- Changes in Regioselectivity of H Atom Abstraction during the Hydroxylation and Cyclization Reactions Catalyzed by Hyoscyamine 6β-Hydroxylase
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Hyoscyamine 6β-hydroxylase (H6H) is an αKG-dependent nonheme iron oxidase that catalyzes the oxidation of hyoscyamine to scopolamine via two separate reactions: hydroxylation followed by oxidative cyclization. Both of these reactions are expected to involve H atom abstraction from each of two adjacent carbon centers (C6 vs C7) in the substrate. During hydroxylation, there is a roughly 85:1 preference for H atom abstraction from C6 versus C7; however, this inverts to a 1:16 preference during cyclization. Furthermore, 18O incorporation experiments in the presence of deuterated substrate are consistent with the catalytic iron(IV)-oxo complex being able to support the coordination of an additional ligand during hydroxylation. These observations suggest that subtle differences in the substrate binding configuration can have significant consequences for the catalytic cycle of H6H.
- Ushimaru, Richiro,Ruszczycky, Mark W.,Liu, Hung-Wen
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p. 1062 - 1066
(2019/01/23)
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- A Desymmetrization-Based Total Synthesis of Reserpine
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Reported herein is a desymmetrization-based synthetic approach to the fused polycyclic indole alkaloid reserpine. The centerpiece of the developed strategy features an internal desymmetrization process that enabled the use of a readily accessible and nonstereogenic reserpine E-ring precursor, in contrast to the synthesis-intensive and stereodefined E-ring intermediates employed in all past reserpine syntheses. Utilization of inexpensive reagents through an orchestrated sequence of carefully selected chemical transformations further highlight the overall effectiveness of the developed pathway.
- Park, Jisook,Chen, David Y.-K.
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supporting information
p. 16152 - 16156
(2018/11/23)
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- Stereocontrolled synthesis of a Cn-Cn+7 building block ("eastern moiety") for the unnatural enantiomers of important polyol,polyene antibiotics based on a ring-closing metathesis and an aldol addition of a lactone enolate
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A stereocontrolled synthesis of epoxide 6, which represents the C n-Cn+7 or "eastern moiety" building block for the title compounds, has been realized in 19 steps. Our synthesis started from tetrabromoacetone 26 and afforded dibromotriene 33b in six steps. The latter was subjected to a ring-closing metathesis, which gave the dibromovinyl-substituted lactone 34 in high yield. A highly stereoselective conjugate addition/enolate aldolization sequence established the additional stereocenters with perfect selectivity. Epoxide 47b was reached in another eight steps, which included a C-SiMe2Pha€‰→a€‰C-OH oxidation in the presence of an acetal group. The final structure 6 was completed by hydrostannylation/brominolysis. A dibromovinyl-substituted unsaturated δ-lactone obtained by ring-closing metathesis underwent a highly diastereoselective silyl cuprate 1,4-addition/aldolization sequence. Tamao-Fleming oxidation transformed the silyl into a hydroxy group. Alkyne formation, hydrostannylation, and N-bromosuccinimidolysis converted the dibromovinyl into a trans-bromovinyl moiety. Copyright
- Kamptmann, Sonja B.,Brueckner, Reinhard
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supporting information
p. 6584 - 6600
(2013/11/06)
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- Synthesis of the C38-C44 segment of altohyrtin A - with an addendum on the preparation of 8-oxabicyclo[3,2.1]oct-6-en-3-one
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The densely funtionalized C38-C44 segment F of altohyrtin A with its five contiguous stereogenic centers was prepared in 10 steps and in 28% overall yield (two steps per stereogenic center), from 8- oxabicyclo[3.2.1]oct-6-en-3-one as a template. The preparation of the title compound 1, m.p. 38 °C, is described on a 0.5 m scale in a three-step-two- stage reaction from acetone anti furan. The oxacycle was stored without change at room temperature.
- Kim,Hoffmann
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p. 2195 - 2201
(2007/10/03)
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