Rapid and diverse route to natural product-like biaryl ether containing macrocycles

A two-step sequence involving an Ugi four-component reaction and an intramol. nucleophilic arom. substitution (SNAr) has been developed for the rapid access to biaryl-ether contg. macrocycles. For example, reacting heptanal with butylamine, (3-hydroxyphenyl)acetic acid, and isonitrile I in dry toluene in the presence of NH4Cl gave dipeptide II. II was then cyclized using an intramol. SNAr sequence to give cyclic ether III as a mixt. of 4 diastereomers. In the course of this study, we documented that ammonium chloride can promote the Ugi-4CR in non-polar aprotic solvent (toluene) without the interference of an alternative Passerini reaction. Solid phase synthesis of macrocycles by this two-step sequence was also developed using polymer (Wang resin) supported alpha -(4'-fluoro-3'-nitro)phenethyl isocyanoacetate as one of the inputs. [on SciFinder (R)]


Published in:
Tetrahedron, 59, 40, 7859-7870
Year:
2003
Keywords:
Note:
CAN 140:5292
34-3
Amino Acids, Peptides, and Proteins
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0040-4020
written in English.
75-31-0 (2-Propylamine); 78-84-2 (2-Methylpropanal); 100-46-9 (Benzylamine); 100-52-7 (Benzaldehyde); 104-53-0 (3-Phenylpropanal); 104-94-9 (4-Methoxyaniline); 109-73-9 (Butylamine); 111-71-7 (Heptanal); 120-20-7; 621-37-4 ((3-Hydroxyphenyl)acetic acid); 621-54-5 (3-(3-Hydroxyphenyl)propanoic acid); 3173-56-6 (Benzyl isocyanate); 6326-44-9 (Diethyl formamidomalonate); 7188-38-7 (tert-Butyl isocyanide); 15017-52-4 (4-Fluoro-3-nitrobenzyl bromide); 42564-51-2 (4-Fluoro-3-nitrobenzaldehyde); 58885-60-2; 202120-56-7; 389635-00-1 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of natural-product like biaryl ether macrocycles by soln. and solid-phase Ugi reaction-intramol. nucleophilic arom. substitution); 389634-80-4P; 389634-81-5P; 389634-82-6P; 389634-83-7P; 389635-01-2P; 389635-04-5P; 604004-12-8DP; 604004-12-8P; 604004-13-9P; 627535-77-7P; 627535-78-8P; 627535-81-3DP; 627535-82-4DP; 627535-83-5P; 627535-90-4P; 628308-40-7P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of natural-product like biaryl ether macrocycles by soln. and solid-phase Ugi reaction-intramol. nucleophilic arom. substitution); 389634-85-9P; 389634-86-0P; 389634-89-3P; 389635-02-3P; 389635-05-6P; 389635-06-7P; 390360-55-1P; 390360-57-3P; 390360-59-5P; 390360-61-9P; 604004-08-2P; 604004-09-3P; 604004-10-6P; 604004-14-0P; 604004-15-1P; 604799-74-8P; 604799-75-9P; 627535-74-4P; 627535-79-9P; 627535-80-2P; 627535-85-7P; 627535-86-8P; 627535-87-9P; 627535-88-0P; 627535-89-1P; 627535-91-5P; 627535-92-6P; 627535-93-7P; 628308-41-8P; 628308-42-9P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of natural-product like biaryl ether macrocycles by soln. and solid-phase Ugi reaction-intramol. nucleophilic arom. substitution)
Laboratories:




 Record created 2010-11-25, last modified 2018-03-17


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