Isomerization-Free Matteson Homologations of Substituted Allylboronic Esters.

Substituted allyl derivatives with an internal double bond can be homologated under standard conditions via a 1,2-shift, whereas allylboronic esters with terminal double bonds can also be homologated via a SN' reaction. This allyl isomerization is catalyzed by ZnCl2 and can be suppressed by omitting ZnCl2 during the formation of α-chloroboronic ester. However, in the second step with Grignard reagents, ZnCl2 was added to suppress side reactions of the product formed.

Stereoselective Synthesis of Highly Substituted O-Heterocycles via Matteson Homologation: A Ring-Closing Metathesis Approach.

Matteson homologations of chiral boronic esters with the aid of unsaturated nucleophiles are powerful for gaining access to a range of different O-heterocycles via subsequent ring-closing metatheses. Using this protocol, six- to eight-membered rings become available and almost any position of the ring can be substituted and/or functionalized.

Application of Vinyl Nucleophiles in Matteson Homologations.

The Matteson homologation with vinyl nucleophiles was found to be a versatile tool for the synthesis of highly substituted and functionalized allyl boronic esters. High yields and stereoselectivities are obtained with sterically demanding alkyl boronic esters and/or Grignard reagents. With the application of such vinyl Matteson homologations, the polyketide fragment of lagunamide B is synthesized.

A rapid synthesis of low-nanomolar divalent LecA inhibitors in four linear steps from d-galactose pentaacetate.

Chronic infections with Pseudomonas aeruginosa are associated with the formation of bacterial biofilms. The tetrameric P. aeruginosa lectin LecA is a virulence factor and an anti-biofilm drug target. Increasing the overall binding affinity by multivalent presentation of binding epitopes can enhance the weak carbohydrate-ligand interactions. Low-nanomolar divalent LecA ligands/inhibitors with up to 260-fold valency-normalized potency boost and excellent selectivity over human galectin-1 were synthesized from d-galactose pentaacetate and benzaldehyde-based linkers in four linear steps.

Mono-selective ß-C-H arylation of N-methylated amino acids and peptides promoted by the 2-(methylthio)aniline directing group.

2-(Methylthio)aniline (MTA) directed C(sp3)-H functionalisations are efficient and straightforward protocols for the selective ß-modification of N-methylated amino acids. The decreased reactivity of MTA in comparison with the 8-aminoquinoline (AQ) directing group allows for selective monoarylations in high yields without the formation of side products. The protocol is also suitable for the introduction of highly functionalised side chains onto the C-terminal alanines of dipeptides. The MTA directing group can easily be removed, providing free carboxylic acids as valuable building blocks.

C-H Functionalization of N-Methylated Amino Acids and Peptides as Tool in Natural Product Synthesis: Synthesis of Abyssenine A and Mucronine E.

N-Methylated amino acids and peptides with an 8-aminoquinoline (AQ) directing group can be subjected to stereoselective Pd-catalyzed ß-functionalizations. The best results are obtained with aryl iodides, but alkyl and alkenyl side chains can also be introduced. The AQ protecting group can easily be removed, providing the free carboxylic acid, which can be used directly in peptide couplings. This protocol was used successfully as a key step in the synthesis of the cyclopeptide alkaloids abyssenine A and mucronine E.