Synthesis of Enantiopure ω-(4-Fluorophenyl) 6,11-Methylene Lipoxin B4 Methyl Ester

Synthesis ◽  
2021 ◽  
Author(s):  
Lukas Trippe ◽  
Analuisa Nava ◽  
Andrea Frank ◽  
Dieter Schollmeyer ◽  
Udo Nubbemeyer
Keyword(s):  
Methyl Ester ◽  
Building Blocks ◽  
Optically Active ◽  
Unsaturated Ketone ◽  
Methylene Bridge ◽  
Aromatic Moiety ◽  
Carbon Backbone ◽  
Gain Access

The synthesis of Lipoxin B4 analogs (LXB4) to gain access to stabilized inflammation resolving compounds is an active field of research. Focusing on variation and stabilization of the conjugated E,Z,E,E C6–C13 tetraene moiety of natural LXB4, a methylene bridge introduced between C6 and C11 suppresses any Z/E isomerization of the C8–C9 olefin. Furthermore, rapid ω-oxidation (C20) should be avoided by replacing the C18-C20 segment by an aromatic moiety. Optically active C1–C12 building blocks were accessed from cycloheptatriene 1-carbonester (C6–C11, C21) and glutaryl chloride (C1–C5) as described earlier. The ω-segment had been generated via a five-step sequence starting from 4-arylbutanoic acid. Horner key olefination enabled assembly of the carbon backbone. A final five step sequence including a chelate Cram reduction of the unsaturated ketone moiety afforded the target ω-aryl 6,11-methylene-LXB4 methyl ester.

Synthesis of Optically Active 15-epi-9,14-Methylene Lipoxin A4

Synthesis ◽  
2018 ◽  
Vol 50 (06) ◽  
pp. 1246-1258
Author(s):  
Udo Nubbemeyer ◽  
Adile Duymaz ◽  
Jochen Körber ◽  
Carolin Hofmann ◽  
Dorothea Gerlach
Keyword(s):  
Total Synthesis ◽  
Building Block ◽  
Building Blocks ◽  
Optically Active ◽  
Protecting Groups ◽  
Lipoxin A4 ◽  
Methylene Bridge ◽  
Type Coupling ◽  
Important Field ◽  
Gain Access

The synthesis of lipoxin A4 and B4 analogues (LXA4, LXB4) to gain access to stabilized inflammation resolving compounds is an important field of research. Starting from known structural requirements of the natural compounds displaying biological activity and a broad investigation of their rapid metabolism, various LXA4 derivatives have been developed and tested. Focusing on variation and stabilization of the conjugated E,E,Z,E C7–C14 tetraene moiety of natural LXA4, a methylene bridge introduced between C9 and C14 might suppress any Z/E isomerization of the C11–C12 olefin. Intending to enable at least known structure variations in connection with the C1–C7 and the C15–C20 fragments, a convergent total synthesis starting from a known cycloheptatriene is developed. The C1–C8 building blocks are generated via six-step ex-chiral pool sequences starting from 2-deoxy-d-ribose delivering two 5,6-dihydroxy carboxylic acid derivatives with C7 aldehyde functions. The synthesis of the C8–C21 building block starts from a known cycloheptatriene 1-carbonester (C8–C14, C21) and hexanoyl chloride (C15–C20). After Friedel–Crafts-type coupling, the defined configuration of the C15 OH group is introduced via enantioselective reduction of the ketone precursor. Following an additional four steps, an aryl sulfone C9–C21 building block is completed ready for a key Julia–Kocienski olefination with the C1–C7 compounds. Finally, removal of the protecting groups completes the synthesis of the target optically active 9,14-methylene LXA4 methyl ester.

The synthesis of optically active building blocks carrying an α, α-dihalogeno-β, β, β-trifluoroethyl group

1989 ◽  
Vol 42 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Tomoya Kitazume ◽  
Takeshi Ohnogi ◽  
Jenq Tain Lin ◽  
Takashi Yamazaki ◽  
Keizo Ito
Keyword(s):  
Building Blocks ◽  
Optically Active

Optically Active Functionalized Building Blocks for Peptidyl Olefin Peptidomimetics

2021 ◽  
Vol 6 (31) ◽  
pp. 7912-7918
Author(s):  
Ekaterina Lerman ◽  
Shlomo Levinger ◽  
Amnon Albeck
Keyword(s):  
Building Blocks ◽  
Optically Active

scholarly journals The structure of bacilysin and other products of Bacillus subtillis

1970 ◽  
Vol 118 (4) ◽  
pp. 563-570 ◽  
Author(s):  
J. E. Walker ◽  
E. P. Abraham
Keyword(s):  
Methyl Ester ◽  
Proton Magnetic Resonance Spectrum ◽  
Cotton Effect ◽  
Optical Rotatory Dispersion ◽  
Keto Group ◽  
Spin Splitting ◽  
Unsaturated Ketone ◽  
Epoxide Group ◽  
Group 4 ◽  
Optical Rotatory Dispersion Curve

1. Mass spectra of the trimethylsilyl derivative and the methyl ester of the N-trifluoroacetyl derivative of bacilysin indicated that the antibiotic had a molecular weight of 270. Several peaks in the spectrum of the methyl ester were consistent with the presence of an N-terminal alanine residue in the molecule. 2. The proton-magnetic-resonance spectrum of bacilysin confirmed that the antibiotic contained an epoxide group and the spin–spin splitting of the protons of the epoxide group indicated that the side chain of the epoxycyclohexanone ring was attached at C-4 and was αβ to the keto group. 3. The formation of an αβ-unsaturated ketone on reduction of bacilysin with chromous chloride also showed that the epoxide was αβ to the keto group. 4. The optical-rotatory-dispersion curve of bacilysin showed a positive Cotton effect. On the assumption that the reversed Octant rule for αβ-epoxyketones was applicable this revealed the absolute stereochemistry and enabled a definitive structure to be assigned to the molecule. 5. Similar measurements showed that substance AA1, isolated from culture supernatants, was the C-terminal amino acid of bacilysin. 6. Hydrolysis of substance P2 with leucine aminopeptidase and the mass spectrum of the methyl ester of its N-trifluoroacetyl derivative showed that this substance was l-analyl-l-alanine. 7. These results are discussed in relation to the biogenesis of bacilysin.

Asymmetric reduction of chlorinated 4-oxopentanoates with Bakers' yeast. Synthesis of optically active .gamma.-butyrolactones and useful chiral building blocks

1991 ◽  
Vol 56 (25) ◽  
pp. 7177-7179 ◽  
Author(s):  
Sadao Tsuboi ◽  
Junichi Sakamoto ◽  
Takayuki Kawano ◽  
Masanori Utaka ◽  
Akira Takeda
Keyword(s):  
Asymmetric Reduction ◽  
Building Blocks ◽  
Optically Active

Kinetic resolution of oxime esters with lipases — synthesis of enantiomerically enriched building blocks with quaternary carbon centers and formal total synthesis of perhydro histrionicotoxin

2002 ◽  
Vol 80 (6) ◽  
pp. 686-691 ◽  
Author(s):  
Nicole Diedrichs ◽  
Ralf Krelaus ◽  
Ina Gedrath ◽  
Bernhard Westermann
Keyword(s):  
Substrate Specificity ◽  
Total Synthesis ◽  
Solvent Effects ◽  
Kinetic Resolution ◽  
Building Blocks ◽  
Beckmann Rearrangement ◽  
Optically Active ◽  
Quaternary Carbon ◽  
Carbon Centers

Enantiomerically enriched oximes bearing stereogenic quaternary carbon centers can be obtained by lipase-catalyzed kinetic resolution of oxime esters. Substrate specificity, solvent effects, and the use of different lipases are discussed. Kinetic resolution of butyrylated oximes by lipase PS in the presence of n-butanol gave the best ee-values of both the saponified oxime and the residual oxime ester. Subsequent stereospecific Beckmann rearrangement of an enantiomerically enriched oxime provided lactams, which could be employed for the synthesis of optically active perhydro histrionicotoxin.Key words: oxime, lipase, kinetic resolution, Beckmann rearrangement, perhydro histrionicotoxin.

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