TY - JOUR
T1 - Isocyanide-based multicomponent reactions for the synthesis of heterocycles
AU - Váradi, András
AU - Palmer, Travis C.
AU - Dardashti, Rebecca Notis
AU - Majumdar, Susruta
N1 - Funding Information:
This work was supported by research grants from the National Institute on Drug Abuse (DA034106) to S.M. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and bioconjugation. Traditional isocyanide-based MCRs utilize an external nucleophile attacking the reactive nitrilium ion, the key intermediate formed in the reaction of the imine and the isocyanide. However, when reactants with multiple nucleophilic groups (bisfunctional reactants) are used in the MCR, the nitrilium intermediate can be trapped by an intramolecular nucleophilic attack to form various heterocycles. The implications of nitrilium trapping along with widely applied conventional isocyanide-based MCRs in drug design are discussed in this review.
AB - Multicomponent reactions (MCRs) are extremely popular owing to their facile execution, high atom-efficiency and the high diversity of products. MCRs can be used to access various heterocycles and highly functionalized scaffolds, and thus have been invaluable tools in total synthesis, drug discovery and bioconjugation. Traditional isocyanide-based MCRs utilize an external nucleophile attacking the reactive nitrilium ion, the key intermediate formed in the reaction of the imine and the isocyanide. However, when reactants with multiple nucleophilic groups (bisfunctional reactants) are used in the MCR, the nitrilium intermediate can be trapped by an intramolecular nucleophilic attack to form various heterocycles. The implications of nitrilium trapping along with widely applied conventional isocyanide-based MCRs in drug design are discussed in this review.
KW - Heterocycles
KW - Nitrilium trapping
KW - Ugi reaction
UR - http://www.scopus.com/inward/record.url?scp=85000788446&partnerID=8YFLogxK
U2 - 10.3390/molecules21010019
DO - 10.3390/molecules21010019
M3 - Review article
C2 - 26703561
AN - SCOPUS:85000788446
SN - 1420-3049
VL - 21
JO - Molecules
JF - Molecules
IS - 1
M1 - 19
ER -