Hugues Bienayme

A New Heterocyclic Multicomponent Reaction For the Combinatorial Synthesis of Fused 3-Aminoimidazoles

When general and reliable, multicomponent reactions are among the most powerful tools in modern drug discovery. The principle of chemical ligation of reactive partners (see reaction scheme) has been employed to find a new, highly efficient synthesis of fused 3-aminoimidazoles.

A Five-Component Synthesis of Hexasubstituted Benzene†

A one-pot, 5-component, domino process was used to prep. 7 hexasubstituted benzenes, e.g., I, in 32-67% yield. The 5 components for I were BuNH2, heptanal, isocyanide II, PhC==CCO2C6F5, and N-phenylmaleimide. The process creates 7 chem. bonds and delivers 5 elements of diversity into the compact polyheterocycle. [on SciFinder (R)]

Synthesis of rigid hydrophobic tetrazoles using an Ugi multi-component heterocyclic condensation

Abstract A highly convergent four-component, two-step, one-pot reaction between an aldehyde, a primary amine, an alkyl-β-(N,N-dimethylamino)-α-isocyanoacrylate and hydrazoic acid to form a substituted bicyclic tetrazole is disclosed. Vast arrays of small organic « drug-like a molecules can be combinatorially prepared with such transformation.

Eine neue heterocyclische Mehrkomponentenreaktion für die kombinatorische Synthese von anellierten 3‐Aminoimidazolen

Mehrkomponentenreaktionen gehoren – wenn sie allgemein anwendbar sind und zuverlassig ablaufen – wohl zu den leistungsfahigsten Werkzeugen der modernen Wirkstoffsuche. Dem Prinzip der chemischen Verknupfung reaktiver Partner (siehe Schema) folgend wurde nun eine neue, hocheffiziente Synthese anellierter 3-Aminoimidazole entwickelt.

Total Synthesis of (+)-Crocacin C Using Hidden Symmetry

A highly convergent and protecting-group-free synthesis of (+)-crocacin C, featuring an enzymatic enantioselective desymmetrization of a meso-diol, a base-induced ring opening of a THP ring, and a one-pot hydrostannylation/Stille coupling as the key steps, is reported. The natural product was obtained in 11 steps and 22.3% overall yield starting from readily available oxabicycle 1. Finally, a unique enantioselective step, an enzymatic desymmetrization, revealed four stereogenic centers and created one in C4 of the THP furnishing the dense building block 4 with high enantioselectivity (ee >98%).

Library Generation via Postcondensation Modifications of Isocyanide-Based Multicomponent Reactions

Publisher Summary This chapter focuses on a particular branch of multicomponent condensation reaction (MCR) methodologies— namely, the postcondensation modifications (or secondary reactions) of isocyanide-based multicomponent reactions (IMCRs). One attractive feature of the multicomponent reaction is the relative ease of its automation. Discrete reactions may be run in parallel by either solution- or solid-phase protocols in a standard 96-well format. One of the methodologies discussed in the chapter is the UDC (Ugi/De-Boc/Cyclize) methodology. The biological utility of 1,4-benzodiazepine-2,5-diones (BDPs) appears in many areas, including the applications as antagonists of the platelet glycoprotein IIb-IIIa, anticonvulsant agents, antihypnotic agents, reverse transcriptase inhibitors, and selective cholecystokinin (CCK) receptor subtype A or B antagonists. The chapter presents three miscellaneous postcondensation modification reactions: (1) TMSN 3 modified Ugi Reactions, (2) postcondensation Passerini reactions, and (3) TMSN 3 -modified Passerini reaction. The TMSN 3 -modified Ugi reaction involves the condensation of an appropriately substituted aldehyde or ketone with a primary or secondary amine.

“Reagent explosion”: an efficient method to increase library size and diversity

Abstract Methyl-β-(N, N-dialkylamino)-α-isocyanoacrylates, readily prepared from the reaction between various secondary amines, N-formylimidazole diethylacetal and methyl isocyanoacetate, can be used to increase the diversity of the isonitrile input in multi-component condensation, such as the Passe´rini reaction.

Palladium-catalysed vinylation of tertiary allylic alcohols: a new protocol for the synthesis of isoprenoid aldehydes.

Abstract Heck vinylation of tertiary allylic alcohols with iodo-acetal Ic , followed by an acid catalysed acetal hydrolysis-dehydration reaction, furnished isoprenoid aldehydes regioselectively in high yields.

Enantioselective enzymatic desymmetrization of highly functionalized meso tetrahydropyranyl diols.

The enantioselective enzymatic desymmetrization of several highly substituted meso-tetrahydropyranyl diols is described. This transformation leads to valuable building blocks containing up to five stereogenic centers, which are revealed in a single step with both high yields and excellent enantiomeric excesses. Moreover, it was shown that this kind of building blocks could provide an easy access to both enantiomers of highly functionalized stereotetrads.

Efficiency of organometallic catalysis in a new “ecological” synthesis of retinal

Abstract Isoprenoid aldehydes (such as retinal) are readily obtained from propargylic alcohols by a three step protocol involving the key palladium-catalysed transformation 1 → 2