Synthetic studies towards the novel neurotrophic diterpenoids neovibsanins A and B: construction of the ABC core

A concise, general approach to the tricyclic furo-furan-based core structure present in the bioactive natural products neovibsanins A and B, from readily available Baylis-Hillman adducts, is delineated.     

Synthetic studies towards atkamine

Atkamine is a complex marine pyrroloiminoquinone alkaloid that comprises a heptacyclic scaffold bearing five different heterocycles and four contiguous stereocenters,and therefore it is a highly challenging target for synthetic chemists.We herein reported a modular synthetic strategy toward this alkaloid,featuring a formal [5+2] annulation and an asymmetric Michael addition.The efficient synthesis of the long-chain aliphatic aldehyde and chiral amino acetal fragments have been achieved.A simplified tetracyclic intermediate bearing the core structure of atkamine has been successfully constructed through the formal [5+2] annulation.     

Synthetic studies towards the pectenotoxins: a review

In this article we provide an overview of synthetic studies towards pectenotoxins (PTXs) that have been reported by several research groups. The difficulties encountered in the synthesis of these series of polyketides are highlighted by the fact that only one total synthesis of PTX4 and PTX8 has been completed to date. The strategies used in the critical bond forming steps and the introduction of key stereogenic centres are compared and contrasted.     

Synthetic studies towards picrasane quassinoids

An advanced intermediate 40 with the ABC ring of the picrasane quassinoid skeleton has been synthesised from ent-halimic acid. The bicyclic system of the starting material has been incorporated as the BC part of the ABC system. Until date, no diterpenes of the antipode series have been used in this kind of approach.     

Synthetic studies towards diazepanone scaffolds

The synthesis of new enantiopure polyfunctionalised diazepanone scaffolds is described. The key steps involve the opening of an azido-epoxide C4 building block derived from l-ascorbic or d-isoascorbic acid by a l-serine derivative followed by a lactonisation–lactamisation two-step sequence.     

Synthetic studies towards ptilomycalin A: total synthesis of crambescidin 359

A potentially biomimetic synthesis of the guanidine-containing marine natural product crambescidin 359 via a double Michael addition of guanidine to a suitably functionalised bis-enone is reported.     

Synthetic studies towards the ent-labdane diterpenoids: rearrangement of ent-halimanes

For the first time ent-labdanes have been synthetised starting from ent-halimic acid, following a route that is the reverse of the biosynthetic one leading to the former compounds.     

Synthetic studies toward FR182877. Remarkable solvent effect in the vinylogous morita-baylis-hillman cyclization

[reaction: see text]. The intramolecular vinylogous Morita-Baylis-Hillman reaction was explored to access the central cyclopentane ring of FR182877. The reaction manifold and product distribution is strikingly solvent and substrate dependent.     

Synthetic studies towards the benzophenone precursor for balanol

Synthesis of 4-carboxy-2,6-dimethoxyphenyl 2′-carboxy-6′-methoxyphenyl ketone, an important precursor for balanol's benzophenone portion, has been achieved via a short and efficient route in three steps using ortho-lithiation as the key step. In another approach aromatization of 2-(2′-methoxy-6′-methylbenzoyl)-5-methyl-1,3-cyclohexanedione afforded benzophenone precursor 2,6-dimethoxy-4-methylphenyl 2′-methoxy-6′-methylphenyl ketone along with the formation of substituted xanthone.     

Synthetic studies towards lagunamide C: Polyketide assembly investigations

Lagunamide C is a depsipeptide natural product with low nM cytotoxicity towards numerous cancer cell lines. Synthetically, it is disconnected to a pentapeptide backbone and polyketide unit that possesses four stereogenic centers, of which two of centers are in question (C38 & 40). Our model system highlights a high-selective aldol addition via a Crimmin’s auxiliary setting the C40 ester linkage, and a non-facially selective cyclopropanation with subsequent ring opening for the installation of the C38 methyl center.     

Equilibrium between a vinylogous ylide and a phosphonium dienolate zwitterion: vinylogous Wittig olefination versus vinylogous aldol-type reaction

This paper describes the equilibrium established between a phosphonium dienolate zwitterion and a vinylogous phosphorus ylide, and their reactions with aldehydes. The reactions between ethyl 2-methyl-2,3-butadienoate and various aldehydes occur through either a phosphonium dienolate or a vinylogous ylide intermediate, depending on the presence/absence of a Lewis acid and the nature of the phosphine. We observed a rare vinylogous Wittig olefination from the reaction between ethyl 2-methyl-2,3-butadienoate and an electron-deficient aromatic aldehyde in the presence of a stoichiometric amount of an electron-deficient triarylphosphine and a catalytic amount of a Lewis acid (e.g., BF₃·Et₂O). On the other hand, the use of triphenylphosphine, in the absence of a Lewis acid, facilitated vinylogous aldol addition, accompanied by a rare 1,2-aryl phosphorus-to-carbon migration.     

Synthetic studies towards the novel fomannosane sesquiterpenoid illudosin: framework construction

A synthetic approach to the novel fomannosane sesquiterpene natural product illudosin 2 from the diquinane precursor 5, readily available in turn from commercial 1,5-cyclooctadiene, is delineated. The key steps are the stereoselective construction of the cis, anti, cis-tricyclo[6.2.0.0^2,6]decane system, strategic C-C bond disengagement through Baeyer-Villiger oxidation and functional group adjustments to deliver the carbocyclic core 18 present in the natural product.     

Synthetic studies towards furanocembrane diterpenes. A total synthesis of bis-deoxylophotoxin

Synthetic approaches to the furanocembrane family of natural products, e.g. lophotoxins, pukalides, bipinnatins, based on: i) an intramolecular cyclisation of an alpha,beta-unsaturated acyl radical intermediate into a conjugated enone, and ii) an intramolecular Stille coupling reaction involving a 2-stannylfuran and a vinyl iodide, are described. A total synthesis of bis-deoxylophotoxin , the probable biological precursor to the neurotoxin lophotoxin, isolated from species of the Pacific sea whip Lophogorgia, is then presented.     

Synthetic studies towards the acyltetronic acid iohophore M 139603

The synthesis of the optically pure tetrahydrofuran fragment of the acyltetronic acid ionophore M139603 from (S)-(+)-methyl-3-hydroxy-2-methylpropionate is described and its comparison made with authentic material derived from the natural product by degradation.     

Synthetic Studies towards the Calcium-Dependent Lipopeptide Antibiotic Cadaside B

In the current global crisis of antimicrobial resistance, antimicrobial peptides represent a promising source of alternative antibiotics. Recently discovered cadaside B, a novel calcium-dependent antibiotic, exhibits potent antimicrobial activity towards Gram-positive pathogens including multi-drug resistant strains. These properties, coupled with a novel structure, non-cytotoxicity, and low likelihood of developing resistance render cadaside B an important synthetic target. Herein, a synthetic strategy towards cadaside B is reported with the key steps involving on-resin depsipeptide bond formation and solution-phase macrolactamization. Good agreement of the synthetic cadaside B MS/MS fragmentation pattern was observed with the natural product, but a different ¹H NMR spectrum and absence of antimicrobial activity suggest an undetected epimerization event took place during the synthesis. Herein the findings of our synthetic journey and suggestions for future directions are presented.     

Synthetic studies towards dendridine A: synthesis of hemi-dendridine A acetate by Fischer indolization

A short synthesis of hemi-dendridine A acetate has been accomplished. The synthesis is based on a modified Fischer indolization that represents a rare example of the single-step synthesis of a 7-oxytryptamine from an ortho-oxygenated phenylhydrazine. The synthetic route required developing an efficient synthesis of N-acetyl-2-pyrroline, the key coupling partner for the modified Fischer indolization. Some interesting chemistry associated with the abnormal Fischer indolization has been uncovered, whereby two molecules of the phenylhydrazine substrate combined along the abnormal reaction pathway, affording an unusual N-phenylindoleamine product.     

A new three-step domino Knoevenagel-hetero-Diels-Alder oxidation reaction

A new catalyst-free domino Knoevenagel-hetero-Diels-Alder oxidation reaction is reported. 6H-Chromeno[4′,3′:4,5]thiopyrano[2,3-d][1,3]thiazol-4-ium-2-olates are formed in good yields via reaction of 2-(2-propynyloxy)benzaldehydes with 4-thioxo-1,3-thiazolidin-2-one.     

The organocatalytic vinylogous aldol reaction: recent advances

Over the past decade, organocatalysis has emerged as a powerful tool for stereoselective carbon-carbon bond formation under exceptionally mild conditions. The organocatalytic versions of a large number of traditional synthetic transformations are now well established and the quest for new applications of the basic concepts of organocatalysis continues. This review addresses the emergent interest in the organocatalytic vinylogous aldol reaction. While noteworthy progress has been made in this area, significant challenges lie ahead.     

Synthetic studies towards the mulberry Diels-Alder adducts: H-bond accelerated cycloadditions of chalcones

The methyl ether derivatives 2, 4 and 6 of the mulberry Diels-Alder adducts chalcomoracin (1) and mulberrofuran C (3) and kuwanon J (5) respectively have been synthesized by a thermal [4 + 2]-cycloaddition reaction between a chalcone and dehydroprenyl diene. A H-bonded ortho OH substituent on the chalcone was found to be essential for Diels-Alder reactivity. Density functional theory calculations show that the OH group lowers the barrier for the Diels-Alder reaction by 2-3 kcal mol(-1) compared with OMe. The acceleration by the OH group is traced to two transition-state effects: a stronger diene-chalcone interaction and better planarity of the aryl-diene unit.