Matthew M. Abelman

Cyclic ketones and substituted α-keto acids as alternative substrates for novel Biginelli-like scaffold syntheses

The reactions of benzocyclic ketones and α-ketoacids as carbonyl components in the Biginelli reaction were investigated. These unusual Biginelli substrates furnished novel drug-like dihydropyrimidinone scaffolds suitable for further elaboration.

Claisen-rearrangement-mediated ring contraction of macrocyclic lactones : A new approach to carbocycles and heterocycles

Abstract Macrocyclic ketene acetals 3 undergo Claisen rearrangements smoothly and constitute a viable and general approach to hetero- or carbocyclic ring systems 4 . This novel ring contraction process is subject to high internal asymmetric induction (cf. lactones 7 → carbocycles 8 ) as well as relative asymmetric induction in the rearrangements of ketene acetals derived from lactones 18 , 23 and 27 . Finally, N-benzoylmeroquinene methyl ester ( 37 ) was prepared to demonstrate the potential of this methodology in heterocycle synthesis.

Architecturally diverse heterocycle formation by N-acyliminium ion initiated cyclization

Enaminoesters containing a tethered indole or aryl moiety on the amine react with substituted maleic anhydrides or acryloyl chlorides to provide pyrrolinone or dihydropyridone products, respectively. The indole-tethered dihydropyridones can be induced to undergo a one-pot cyclization whereas, the indole-tethered pyrrolinone intermediates are readily cyclized with HCl. The aryl-tethered pyrrolinones or dihydropyridones can be isolated and subsequently induced to cyclize with triflic acid. This methodology culminates in the synthesis of erythrane-like and other natural products that are readily amenable to combinatorial library production.

Preparation of bridged bicycloalkanes via intramolecular [2+2] cycloadditions of ketenes a short total synthesis of (±)-clovene

Abstract The preparation of a bridged bicyloalkane via an intramolecular ketene-olefin cycloaddition reaction in the context of a total synthesis of clovene is described.

The synthesis of 2-ketopiperazine acetic acid esters and amides from ethylenediamines with maleates and maleimides

The reaction of substituted ethylenediamines with various fumarates, maleates, and maleimides to form substituted ketopiperazine acetic acid esters and amides was investigated. This method affords a straightforward, high yield approach to a variety of potential peptidomimetics and can yield surprising results with regard to regio- and stereoselectivity.

Synthesis and agrochemical screening of a library of natural product-like bicyclo[2,2,2]octenones

A general route to a series of differentially substituted bicyclo[2,2,2]octenones has been developed, making use of the in situ intramolecular Diels Alder reaction of masked ortho-benzoquinones. This approach was used to synthesize a series of thirteen key acid-containing templates from which a solution phase discovery library of 1126 diverse amides was then constructed. The rigid polycyclic nature of the templates and the prevalence of oxygenated functionality confer natural product-like qualities and three-dimensional diversity. The library was screened in HTS in vivo against a number of weed, insect and fungal model organisms leading to the discovery of a novel series of herbicidally active compounds. The development, production and biological activity of the library are described.