Concise Stereoselective Total Synthesis of (+)-Mueggelone

Kumar, D. Aravind; Meshram, H. M.

doi:10.1080/00397911.2011.624395

Cited by 10 publications

(5 citation statements)

References 10 publications

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“…First, aldehyde 6 was prepared from commercially available cis -hex-3-en-1-ol in several steps, including a Katsuki-Sharpless asymmetric epoxidation reaction (Supporting Information). 15 The absolute configuration set in the epoxidation process was assured via correlation with previously reported data. 16 An E -selective Wittig reaction 17 between 6 and the commercially available ylide (triphenylphosphoranylidene)acetaldehyde ( 7 ) furnished stereochemically pure aldehyde 8 in 61% yield after chromatographic purification.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of the 16S,17S-Epoxyprotectin Intermediate in the Biosynthesis of Protectins by Human Macrophages

et al. 2015

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The n-3 polyunsaturated fatty acids act as substrates during the resolution phase of acute inflammation for the biosynthesis of specialized pro-resolving lipid mediators. One premier example is the C22-dihydroxy-polyunsaturated fatty acid protectin D1 (1). The human 15-lipoxygenase type I, via stereoselective processes and with docosahexaenoic acid as the substrate, enables the formation of this specialized pro-resolving lipid mediator. Herein, based on results from LC/MS-MS metabololipidomics, support is presented for the apprehended biosynthesis of 1 in human macrophages occurs via the intermediate 16S,17S-epoxy-protectin (5). Stereochemical pure 5 was obtained using the Katsuki-Sharpless epoxidation protocol, establishing the chirality at the C16 and C17 atoms, one Z-selective reduction as well as E- and Z-stereoselective Wittig reactions. In addition, information on the non-enzymatic aqueous hydrolysis products and the half-life of 16S,17S-epoxy-protectin (5) is presented.

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Section: Resultsmentioning

confidence: 99%

Synthesis of the 16S,17S-Epoxyprotectin Intermediate in the Biosynthesis of Protectins by Human Macrophages

et al. 2015

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“…

Chiral allylic alcohols of w-alkenoic acids and derivatives thereof are highly important building blocks for the synthesis of biologically active compounds. [2] A chemoenzymatic route with an alcohol dehydrogenase catalyzed selective reduction as the key step was reported by our group and represents arguably the most efficient access nowadays (2 or 3 steps, 73-77 % overall yield, > 99 % ee, both enantiomers accessible). Described herein is an enzymatic approach using the P450 BM3 monooxygenase mutant A74G/L188Q, which catalyzes allylic hydroxylation with high to excellent chemo-and enantioselectivities providing the desirable secondary alcohols.

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mentioning

confidence: 99%

“…[1] Extensive research toward the enantioselective synthesis of these moieties has resulted in multistep approaches comprising prefunctionalization and protection group chemistry as well as functional group interconversions and oxidation state manipulations. [2] A chemoenzymatic route with an alcohol dehydrogenase catalyzed selective reduction as the key step was reported by our group and represents arguably the most efficient access nowadays (2 or 3 steps, 73-77 % overall yield, > 99 % ee, both enantiomers accessible). [3] Significant streamlining could be achieved by the direct asymmetric oxidation of readily available "unactivated" olefins at the allylic position, providing a highly atom-economic single-step process.…”

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confidence: 99%

Enantioselective Allylic Hydroxylation of ω‐Alkenoic Acids and Esters by P450 BM3 Monooxygenase

2014

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Chiral allylic alcohols of ω-alkenoic acids and derivatives thereof are highly important building blocks for the synthesis of biologically active compounds. The direct enantioselective C-H oxidation of linear terminal olefins offers the shortest route toward these compounds, but known synthetic methods are limited and suffer from low selectivities. Described herein is an enzymatic approach using the P450 BM3 monooxygenase mutant A74G/L188Q, which catalyzes allylic hydroxylation with high to excellent chemo- and enantioselectivities providing the desirable secondary alcohols.

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“…The methyl ester of 16 S ,17 S -ePD n-3 DPA was constructed via two key precursors ( Figure 3 A). These precursors were obtained using the following stereoselective reactions: a Katsuki-Sharpless epoxidation protocol ( Kumar and Meshram, 2013 ) and one Z - and two E -selective Wittig reactions ( Maryanoff and Reitz, 1989 ). The detailed description of the synthetic route is reported in Primdahl et al.…”

Section: Resultsmentioning

confidence: 99%

PDn-3 DPA Pathway Regulates Human Monocyte Differentiation and Macrophage Function

Pistorius

Souza

Matteis

et al. 2018

Cell Chemical Biology

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SummaryMacrophages are central in orchestrating the clearance of apoptotic cells and cellular debris during inflammation, with the mechanism(s) regulating this process remaining of interest. Herein, we found that the n-3 docosapentaenoic acid-derived protectin (PDn-3 DPA) biosynthetic pathway regulated the differentiation of human monocytes, altering macrophage phenotype, efferocytosis, and bacterial phagocytosis. Using lipid mediator profiling, human primary cells and recombinant enzymes we found that human 15-lipoxygenases initiate the PDn-3 DPA pathway catalyzing the formation of an allylic epoxide. The complete stereochemistry of this epoxide was determined using stereocontrolled total organic synthesis as 16S,17S-epoxy-7Z,10Z,12E,14E,19Z-docosapentaenoic acid (16S,17S-ePDn-3 DPA). This intermediate was enzymatically converted by epoxide hydrolases to PD1n-3 DPA and PD2n-3 DPA, with epoxide hydrolase 2 converting 16S,17S-ePDn-3 DPA to PD2n-3 DPA in human monocytes. Taken together these results establish the PDn-3 DPA biosynthetic pathway in human monocytes and macrophages and its role in regulating macrophage resolution responses.

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Concise Stereoselective Total Synthesis of (+)-Mueggelone

Cited by 10 publications

References 10 publications

Synthesis of the 16S,17S-Epoxyprotectin Intermediate in the Biosynthesis of Protectins by Human Macrophages

Synthesis of the 16S,17S-Epoxyprotectin Intermediate in the Biosynthesis of Protectins by Human Macrophages

Enantioselective Allylic Hydroxylation of ω‐Alkenoic Acids and Esters by P450 BM3 Monooxygenase

PDn-3 DPA Pathway Regulates Human Monocyte Differentiation and Macrophage Function

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