François Guibé

Use of Alloc-amino acids in solid-phase peptide synthesis. Tandem deprotection-coupling reactions using neutral conditions

Abstract The use of Alloc group in SPPS for the Nα protection of amino acids is an alternative to the Boc and Fmoc protecting groups. The smooth removal of Alloc group in neutral conditions with catalytic amounts of Pd(PPh3)4 in the presence of PhSiH3 as a scavenger for the allyl system permits orthogonality with the most common protecting groups. Furthermore, a tandem deprotection-coupling reaction allows the suppression of DKP formation in cases where this side reaction is troublesome.

New allyl group acceptors for palladium catalyzed removal of allylic protections and transacylation of allyl carbamates

Abstract Allyl carboxylates, carbamates and phenoxides may be cleaved or transacylated in the presence of palladium catalyst and either phenyltrihydrosilane or N-methyl-N-(trimethylsilyl)-trifluoroacetamide. These reactions are totally compatible with the presence of Boc and, as far as phenyltrihydrosilane is concerned, Fmoc protections.

On the use of silylated nucleophiles in the palladium catalysed deprotection of allylic carboxylates and carbamates

Abstract Palladium catalysts and silylamines, used together with a silylating electrophile (trimethylsilyl acetate), allow the deprotection of allyl carbamates under very mild and selective conditions.

Palladium-catalyzed reaction of tributyltin hydride. Selective and very mild deprotection of allyl and allyloxycarbonyl derivatives of amino-acids.

Abstract Allyl(All) and Allyloxycarbonyl(Alloc) amino-acid derivatives are deprotected through palladium-catalyzed hydrostannolysis by Bu 3 SnH in a highly selective manner. Benzyl and benzyloxycarbonyl groups are stable under these conditions. Moreover the allyl and Alloc groups seem orthogonal to the t-butyl and t-butoxycarbonyl protecting groups.

Solid-phase synthesis of peptides using allylic anchoring groups 2. Palladium-catalysed cleavage of Fmoc-protected peptides

Abstract High yields for the cleavage reaction of Fmoc-protected peptide segments from an allylic handle may be obtained using tributyltin hydride in the presence of (Ph3P)PdCl2 in a 1:1 mixture of DMF/DCM. Alternatively the cleavage reaction may be carried out using NMA as nucleophile in a 2:2:1 mixture of DMSO/THF/0.5M HCl in the presence of (Ph3P)4Pd. The Fmoc group is completely stable to both these cleavage methods.

Regio- and stereoselective reductive opening of diene-ester derived monoepoxides with palladium catalyst and dimethylamine–borane complex

Abstract Monoepoxides of diene-esters are regio- and stereoselectively reduced to homoallylic alcohols by dimethylamine–borane complex in the presence of acetic acid and catalytic amounts of Pd(PPh 3 ) 4 .

Cyclopropane ring formation by an SmI2 mediated cyclisation of δ-halo-α,β-unsaturated esters

Abstract δ-Iodo- and δ-bromo-α,β-unsaturated esters with various substituents at the β- and γ-positions readily cyclise to cyclopropane compounds in the presence of samarium diiodide and a proton source.

Tandem deprotection-coupling of Nα-Alloc-amino acids by use of ternary systems Pd cat./PhSiH3/carboxy-activated amino acid

Abstract Nα-allyloxycarbonyl derivatives of amino acids undergo smooth coupling with various carboxy-activated partners when treated with phenylsilane (PhSiH3) in the presence of catalytic amounts of tetrakis-(triphenylphosphine) palladium.

An access to (Z)-ethylenic pseudodipeptides based on ring-closing metathesis

Abstract A new access to enantiopure (Z)-ethylenic pseudopeptides, starting from the chiral pool of amino acids and enantiopure 2-substituted-but-3-enoic acids is proposed and illustrated by the syntheses of the (Z)-ethylenic pseudopeptidic analogs of l -Phe- l -Phe, l -Phe- d -Phe, l -Phe- l -Val, l -Phe- d -Val and racemic ( ll , dd ) and ( ld , dl ) (phenyl)Gly-Phe. The key-steps of these syntheses are a ring-closing metathesis, catalysed by Grubbs’ ruthenium alkykidene complexes, on diethylenic amides and the hydrolytic cleavage of the resulting dihydropyridones under mild conditions through intermediate formation of cyclic imidates.

Diastereoselective SmI2-mediated cyclisation of δ-oxo-α,β-unsaturated esters to cyclopropanols

In the presence of samarium diiodide and a proton source, δ-oxo-γ,γ-disubstituted-α,β-unsaturated esters readily cyclise with complete diastereocontrol to give anti-cyclopropanol products.