Synthesis of Optically Active Hydroxyalkyl Cycloheptatrienes: A Key Step in the Total Synthesis of 6,11-Methylene-LXB4

AbstractStarting from methyl cycloheptatrienyl-1-carboxylate, 6-acylation was successfully achieved employing glutaryl chloride in the presence of AlCl3 under controlled reaction conditions to furnish keto carboxylic acid product. After protection of this keto carboxylic acid as tert-butyl ester, reagent-controlled enantioselective reductions delivered configuration-defined methyl-6-hydroxylalkyl cycloheptatriene-1-carboxylates with up to 80% ee. Whereas simple NaBH4 reduction of the keto carboxylic acid and subsequent lactonization afforded a methyl-6-tetrahydropyranonyl cycloheptatriene-1-carboxylate. Resolution using chiral HPLC delivered the product enantiomers with up to >99% ee Fin…

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

AbstractThe synthesis of Lipoxin B4 analogues (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 methyl cycloheptatriene-1-carboxylate (C6–C11, C21) and glutaryl chloride (C1–C5) as described earlier. The ω-segment was generated via a five-step sequence starting from 4-…

Synthesis of Optically Active N-(4-Hydroxynon-2-enyl)pyrrolidines: Key Building Blocks in the Total Synthesis of Streptomyces coelicolor Butanolide 5 (SCB-5) and Virginiae Butanolide A (VB-A)

AbstractStarting from 5-methylhexanal and (S)-configured N-propargylprolinol ethers, coupling delivered N-(4-hydroxynon-2-ynyl)prolinol derivatives as mixtures of C4 diastereomers. Resolution of the epimers succeeded after introduction of an (R)-mandelic ester derivative and subsequent HPLC separation. Alternatively, suitable oxidation gave the corresponding alkynyl ketone. Midland reagent controlled diastereoselective reduction afforded a defined configured propargyl alcohol with high selectivity. LiAlH4 reduction and Mosher analyses of the allyl alcohols enabled structure elucidation. The suitably protected products are used as key intermediates in enantioselective Streptomyces γ-butyrola…

Synthesis of (+) and (‐)‐Streptomyces coelicolor Butanolide 5 (SCB‐5)

Synthesis of 1-Palmitoyl-2-((E)-9- and (E)-10-nitrooleoyl)-sn-glycero-3-phosphatidylcholines

Extensive investigation of nitrated phospholipids in connection with various biologically important processes requires reliable access to suitable material. A selective chemical synthesis introducing a defined nitrofatty acid at the sn-2 position of a 2-lyso sn-glycero-3-phosphatidylcholine was developed. Given that the nitroalkene moiety of both reactant nitrofatty acid derivative and the product esters is characterised by particular sensitivity to nucleophile addition and, depending on the intermediate, subsequent olefin isomerisation and retro-Henry-type reaction, a reliable two-step ester formation was introduced. The activation of the nitrofatty acid succeeded after reaction with trich…

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Synthesis of Enantiopure 6,11‐Methylene Lipoxin B4Methyl Ester

CCDC 2077847: Experimental Crystal Structure Determination

Related Article: Lukas Trippe, Analuisa Nava, Andrea Frank, Dieter Schollmeyer, Udo Nubbemeyer|2021|Synthesis|53|3760|doi:10.1055/a-1512-1763

CCDC 2076144: Experimental Crystal Structure Determination

Related Article: Jonas Donges, Sandra Hofmann, Moritz Brüggemann, Andrea Frank, Dieter Schollmeyer, Udo Nubbemeyer|2021|Eur.J.Org.Chem.|2021|3345|doi:10.1002/ejoc.202100497

CCDC 2076145: Experimental Crystal Structure Determination

Related Article: Jonas Donges, Sandra Hofmann, Moritz Brüggemann, Andrea Frank, Dieter Schollmeyer, Udo Nubbemeyer|2021|Eur.J.Org.Chem.|2021|3345|doi:10.1002/ejoc.202100497