The Long, Long Way to Bottromycin

Although discovered already in the middle of last century, the bottromycins are a unique class of natural products, and a real challenge for all kind of researchers trying to get familiar with them. The structure elucidation was a tour de force and last over 50 years. Synthetic approaches were also painful and it was actually the first and so far only synthesis which confirmed/revised the previously proposed structures. Recent investigations on the biosynthetic pathway indicate that the bottromycins belong to the ribosomally synthesized and posttranslational modified peptides, but that also the biosynthesis does not proceed along the “usual way”. This review will cover the development of bottromycin research from the beginning until today, with a focus on synthetic studies, total synthesis and modifications

A Straightforward Synthesis of Polyketides via Ester Dienolate Matteson Homologation

Application of ester dienolates as nucleophiles in Matteson homologations allows for the stereoselective synthesis of highly substituted α,β‐unsaturated δ‐hydroxy carboxyl acids, structural motifs widespread found in polyketide natural products. The protocol is rather flexible and permits the introduction of substituents and functionalities also at those positions which are not accessible by the commonly used aldol reaction. Therefore, this ester dienolate Matteson approach is an interesting alternative to the “classical” polyketide syntheses

Combining Matteson Homologations and Claisen Rearrangements : An Efficient Protocol for Amino Acid Synthesis

The Matteson homologation with vinyl nucleophiles was found to be an efficient and versatile protocol for the synthesis of substituted chiral allyl alcohols in a highly stereoselective fashion. These alcohols can be coupled with N-protected glycine and subsequently subjected to zinc-chelated esterenolate Claisen rearrangements to yield highly substituted unsaturated amino acids. By varying the nucleophiles used in the Matteson homologations, the method allows control over not only the stereogenic centers but also the side-chain substitution pattern in the newly formed γ,δ-unsaturated amino acids

Matteson Homologation of Arylboronic Esters

Commercially available arylboronic acids can easily be converted into chiral boronic esters which can be subjected to Matteson homologations using Grignard reagents. The best results are obtained in one pot protocols without isolation of the α-chloroboronic ester intermediates. Alkoxides can also be used as nucleophiles, but the corresponding homologated boronic esters are found to be not stable

Synthesis of modified miuraenamides : the Ugi approach

Miuraenamides, a group of marine cyclodepsipeptides, closely related to jasplakinolide and geodiamolide are found to accelerate nucleation and polymerization of actin, and therefore interfere with cell division processes, at concentrations in the low nanomolar range. For SAR studies derivatives are synthesized via Ugi reaction, which provides the complete tripeptide fragment in only one step. While a wide range of modifications are possible at the C-terminus of the peptide, variations at the central position are not tolerated. Neither modifications in the polyketide

The Allylic Alkylation of Ketone Enolates

The palladium-catalyzed allylic alkylation of non-stabilized ketone enolates was thought for a long time to be not as efficient as the analogous reactions of stabilized enolates, e. g. of malonates and β-ketoesters. The field has experienced a rapid development during the last two decades, with a range of new, highly efficient protocols evolved. In this review, the early developments as well as current methods and applications of palladium-catalyzed ketone enolate allylations will be discussed

Total synthesis of apratoxin A and B using Matteson's homologation approach

Apratoxin A and B, two members of an interesting class of marine cyclodepsipeptides are synthesized in a straightforward manner via Matteson homologation. Starting from a chiral boronic ester, the polyketide fragment of the apratoxins was obtained via five successive homologation steps in an overall yield of 27% and very good diastereoselectivity. This approach is highly flexible and should allow modification also of this part of the natural products, while previous modifications have been carried out mainly in the peptide fragment

Stereoselective synthesis of five- and six-membered carbocycles via Matteson homologation/ring closing metathesis

The Matteson homologation is found to be a versatile tool for the stereoselective synthesis of polyunsaturated alkyl boronic esters, which are excellent precursors for the construction of five- and six-membered carbocycles via ring-closing metathesis. The high diversity of the Matteson reaction allows for the preparation of highly substituted cyclic boronic esters, which are also suitable for further homologations

A Matteson Homologation‐Based Synthesis of Doliculide and Derivatives

Doliculide belongs to a group of marine cyclodepsipeptides with interesting biological properties. Apart from a halogenated dipeptide, a polyketide fragment containing 5 stereogenic centers is the most eye-catching element. This building block can be synthesized in a highly stereoselective fashion using only one key reaction: the Matteson homologation. This straightforward protocol allows for the introduction of a wide range of substituents at almost any position of a growing carbon chain and it is therefore perfectly suited for the synthesis of derivatives for structure-activity relationship studie

Stereoselective Allylic Alkylations of Amino Ketones and Their Application in the Synthesis of Highly Functionalized Piperidines

Chelated ketone enolates are excellent nucleophiles for allylic alkylations. Electron-withdrawing groups on the allyl moiety allow subsequent intramolecular Michael additions giving rise to piperidines with up to five stereogenic centers