Joullie synthesis

The Joullie, Zhu, and Wessjohann groups reported the synthesis of different M-alkyl ansa-cyclopeptides and the corresponding ansa-cyclopeptoids. These are inspired by natural cyclopeptide alkaloids. The first approaches to combine the Ugi reaction with a macrocyclization toward cyclopeptide alkaloids was done by Joullie and coworkers [73-75]. 

Schumacher KK, Hauze DB, Jiang J, Szewczyk J, Reddy RE, Davis FA, Joullie MM (1999) First Total Synthesis of Astin G. Tetrahedron Lett 40 455... 

Scheme 12.34. Synthesis of furanomycin using a Ugi 4CR, by Joullie and co-workers [122] THF = tetrahydrofuran.

Deprotection of a robust MOM ether amidst a welter of polar and hydrolytically sensitive groups was a challenge confronted by the Joulli group in their synthesis of the antitumour Didemnins.464 Treatment of 249,1 [Scheme 4 249 with bromodimethylborane in dichloromethane at low temperature liberated the desired hydroxyl in 249,2 in 93% yield ... 

This is also a traditional peptide synthesis procedure. Joullie and coworkers [79] used it in the synthesis of the cyclopeptide alkaloid dihydromauritine A (142). As shown in Scheme 47, the linear precursor 140 was treated with p-nitrophenyl trifluoroacetate in pyridine to give the p-nitrophenyl ester. After cleavage of the Boc group, the amino ester was subjected to cyclization in dilute DMF in the presence of hydroxybenztriazole (HOBt) and diisopropylethylamine at 25 °C for 5 days. The cyclic product 141 v/as obtained in 10% yield only. 

In the final stages of the total synthesis of ustiloxin D, M.M. Joullie and co-workers had to install the amide side-chain onto the already assembled macrocycle.To achieve this goal, the macrocyclic primary alcohol was treated with the Dess-Martin periodinane to generate the corresponding aldehyde, which was subsequently treated with sodium chlorite to afford the carboxylic acid. The carboxylic acid was then coupled with the benzyl ester of glycine to complete the installation of the side-chain in 66% yield for three steps. 

The first total synthesis of the 14-membered para ansa cyclopeptide alkaloid (-)-nummularine F was accomplished in the laboratory of M.M. Joullie. The A/3 nitrogen atom was introduced by using the Henry reaction between the 4-formylphenoxy group and the anion of nitromethane, followed by reduction of the nitro group to the corresponding amine. The epimeric benzyl alcohols did not pose a problem since they were dehydrated at the end of the synthetic sequence to give the C1-C2 double bond. 

Cyclopropylamines and their substituted derivatives are important building blocks in a large number of biologically active compounds. The synthesis of potentially biologically active A/,A/-dimethyl bicyclic cyclopropylamines from N-allylamino acid dimethylamides by the intramolecular variant of the Kulinkovich reaction was accomplished by M.M. Joullie and co-workers. 

The Sharpless regioreversed asymmetric aminohydroxylation protocol was used as a key step in the total synthesis of ustiloxin D by M.M. Joullie and co-workers.The ( )-ethyl cinnamate derivative was subjected to in situ generated sodium salt of the N-Cbz chloroamine in the presence of catalytic amounts of the anthraquinone-based chiral ligand to afford the desired A/-Cbz protected (2S,3R)-(3-hydroxy amino ester in good yield and with good diastereoselectivity. 

The potential application of the Ugi four-component reaction for amino acid and polypeptide natural product synthesis was recognized and utilized early on by M.M. Joullie." " A representative example is the total synthesis of (+)-furanomycin, a naturally occurring antibiotic. As the exact stereochemistry of the compound was not confirmed, total synthesis of the natural product and its stereoisomers was used to elucidate the stereochemistry. 

Cao, B., Xiao, D., Joullie, M. M. Synthesis of Bicyclic Cyclopropylamines by Intramolecular Cyclopropanation of N-Allylamino Acid Dimethylamides. Org. Lett. 1999, 1, 1799-1801. 

Joullie et al.m have developed a totally novel and very elegant approach to the synthesis of proline peptides that is based on the Ugi reaction of pyrroline derivatives. 

Joullie et al.10 have synthesized (+)-furanomycin (131) by an asymmetric Ugi reaction. This synthesis led to revision of the assumed structure. 

Li, R, Evans, C.D. and Joullie, M.M. (2005) A convergent total synthesis of ustiloxin D via an unprecedented copper-catalysed ethynyl aziridine ring-opening by phenol derivatives. Organic Letters, 7, 5325-5327. 

The total syntheses of (+)-muscarine chloride, its optically active or racemic diastereoisomers, and analogs have been carried out independently in several laboratories. In most cases carbohydrates or, rarely, amino acids were used as chiral starting materials, enabling stereoselective synthesis. The different synthetic approaches as well as other aspects of muscarine chemistry, occurrence, and pharmacology were discussed in an excellent review by Wang and Joullie (18) in this treatise and earlier by Wilkinson (23). 

Heffner, R.J., and M.M. Joullie Studies Directed Toward the Total Synthesis of 14-Membered Cyclopeptide Alkaloids Synthesis of a Cyclic Precursor to Nummu-larine-F. Tetrahedron Lett., 30, 7021 (1989). 

The ustiloxins, isolated from the fungus Ustilaginoidea virens associated with rice plants, show antimitotic properties by inhibiting microtubule formation (7S0, 781). Structurally, they are characterized by the presence of two peptide bonds and one tmusual tertiary alkyl-aryl ether connection. The first total synthesis of ustiloxin D (1205) was achieved in 2002 (782) by Joullie et al., followed by a shorter synthesis by Wandless et al. (783, 784). Later on, its synthesis was conducted again (785) along with ustiloxin F (1206) (786) in a more convergent manner than previously by Joullie et al. (Scheme 15.2). 

Li P, Evans CD, Joullie MM (2005) A Convergent Total Synthesis of Ustiloxin D via an Unprecedented Copper-Catalyzed Ethynyl Aziridine Ring-Opening by Phenol Derivatives. Org Lett 7 5325... 

Li P, Evans CD, Forbeck EM, Park H, Bai R, Hamel E, Joullie MM (2006) Total Synthesis and Biological Evaluation of Ustiloxin Natural Products and Two Analogs. Biowg Med... 

Joullie MM, Thompson TR, and Nemeroff NH (1991) Ninhydrin and ninhydrin analogs. Synthesis and applications. Tetrahedron 47 8791-8830. 

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