Madeleine M. Joullié

Grignard reactions to chiral oxazolidine aldehydes

Abstract Modest to high levels of asymmetric induction are observed with Grignard additions to Garner type aldehydes. The resultant secondary alcohols are important precursors of chiral building blocks for asymmetric synthesis and we have demonstrated that they can be readily converted into their respective γ-hydroxy-β-amino alcohols and β-hydroxyamino acids. Additionally, aryloxy ethers, important components of many natural products, can be obtained from these precursors.

The development of novel ninhydrin analogues.

Following its discovery by Siegfried Ruhemann in 1910, ninhydrin rapidly became a practical analytical tool. In 1954 it was found to be an important reagent to develop fingerprints on porous surfaces. Since its use in forensic chemistry, many efforts have focused on improving the reagent. Many of the shortcomings of ninhydrin have been met by the synthesis of a variety of ninhydrin analogues. This tutorial review provides a short introduction to ninhydrin and highlights the different synthetic approaches used in the development of analogues for the detection of latent fingerprints.

A central strategy for converting natural products into fluorescent probes

A Central Strategy for Converting Natural Products into Fluorescent Probes Matthew D. Alexander, Michael D. Burkart, Michael S. Leonard, Padma Portonovo, Bo Liang, Xiaobin Ding, Madeleine M. Joulli!, Brian M. Gulledge, James B. Aggen, A. Richard Chamberlin, Joel Sandler, William Fenical, Jian Cui, Santosh J. Gharpure, Alexei Polosukhin, Hai-Ren Zhang, P. Andrew Evans, Adam D. Richardson, Mary Kay Harper, Chris M. Ireland, Binh G. Vong, Thomas P. Brady, Emmanuel A. Theodorakis, and James J. La Clair*

1,2-INDANEDIONES : NEW REAGENTS FOR VISUALIZING THE AMINO ACID COMPONENTS OF LATENT PRINTS*

A new class of reagents, 1,2-indanediones, was evaluated for latent print visualization on paper. Tests were carried out for fingerprints and amino acid stains. Selected 1,2-indanediones give fluorescent development superior to DFO. Zinc salt treatment further enhances the sensitivity. The new reagents can be obtained from inexpensive starting materials in a short reaction sequence.

Cyclopeptide alkaloids: chemistry and biology

Recent progress in the synthesis and investigation of the biological activities of cyclopeptide alkaloids is reviewed. New strategies have been devised to overcome some of the synthetic challenges inherent in the formation of strained paracyclophanes. However, issues remain which offer opportunities for the application of catalytic enantioselective organometallic reactions. Members of this class of natural products have been isolated from various parts of a wide variety of plants and researchers will likely continue to show great interest in their formation and function. The biological properties of certain members of this class warrant further investigation. To gain additional insight into these areas, continuing development of synthetic methodology will be essential.

Model studies directed toward the total synthesis of 14-membered cyclopeptide alkaloids: synthesis of prolyl peptides via a four-component condensation

The general applicability of a four-component condensation for the formation of N-acyl-β-aryloxyprolines has been demonstrated in several model studies. The relative stereochemistry of the diastereoisomers obtained has been assigned from 1H n.m.r. studies, and confirmed by an X-ray analysis of one of the stereoisomers.

Synthetic studies of didemnins. II. Approaches to statine diastereomers

Abstract A short and efficient route to (3S,4R)-statine has been developed in connection with synthetic studies toward didemnins A,B and C.

Structural plasticity of tubulin assembly probed by vinca-domain ligands.

Vinca-domain ligands are compounds that bind to tubulin at its inter-heterodimeric interface and favour heterogeneous protofilament-like assemblies, giving rise to helices and rings. This is the basis for their inhibition of microtubule assembly, for their antimitotic activities and for their use in anticancer chemotherapy. Ustiloxins are vinca-domain ligands with a well established total synthesis. A 2.7 Å resolution structure of ustiloxin D bound to the vinca domain embedded in the complex of two tubulins with the stathmin-like domain of RB3 (T(2)R) has been determined. This finding precisely defines the interactions of ustiloxins with tubulin and, taken together with structures of other vinca-ligand complexes, allows structure-based suggestions to be made for improved activity. These comparisons also provide a rationale for the large-scale polymorphism of the protofilament-like assemblies mediated by vinca-domain ligands based on local differences in their interactions with the two tubulin heterodimers constituting their binding site.

Evolution of the total syntheses of ustiloxin natural products and their analogues.

Ustiloxins A-F are antimitotic heterodetic cyclopeptides containing a 13-membered cyclic core structure with a synthetically challenging chiral tertiary alkyl-aryl ether linkage. The first total synthesis of ustiloxin D was achieved in 31 linear steps using an S(N)Ar reaction. An NOE study of this synthetic product showed that ustiloxin D existed as a single atropisomer. Subsequently, highly concise and convergent syntheses of ustiloxins D and F were developed by utilizing a newly discovered ethynyl aziridine ring-opening reaction in a longest linear sequence of 15 steps. The approach was further optimized to achieve a better macrolactamization strategy. Ustiloxins D, F, and eight analogues (14-MeO-ustiloxin D, four analogues with different amino acid residues at the C-6 position, and three (9R,10S)-epi-ustiloxin analogues) were prepared via the second-generation route. Evaluation of these compounds as inhibitors of tubulin polymerization demonstrated that variation at the C-6 position is tolerated to a certain extent. In contrast, the S configuration of the C-9 methylamino group and a free phenolic hydroxyl group are essential for inhibition of tubulin polymerization.

Synthesis of functionalized tetrahydrofurans

Abstract A novel cyclization reaction is described which affords readily manipulable 3(2H)-dihydrofuranone ethylene ketals, useful in the total synthesis of an ascofuranone model, bullatenone, and muscarine analogs.