Synthesis of a unique isoindoline/tetrahydroisoquinoline-based tricyclic sultam library utilizing a Heck-aza-Michael strategy.
The synthesis of a unique isoindoline- and tetrahydroisoquinoline (THIQ)-containing tricyclic sultam library, utilizing a Heck-aza-Michael (HaM) strategy is reported. Both isoindoline and THIQ rings are installed through a Heck reaction on a vinylsulfonamide, followed by one-pot deprotection and intramolecular aza-Michael reaction. Subsequent cyclization with either paraformaldehyde condensation or 1,1'-carbonyldiimidazole coupling generates a variety of tricyclic sultams. Overall, a 160-member library of these sultams, together with their isoindolines/THIQ and secondary sulfonamides precursors, were constructed using this strategy.
Department of Chemistry, University of Kansas, Lawrence, 66045-7582, United States.
Qin
Q
Zang
Salim
S
Javed
Patrick
P
Porubsky
Farman
F
Ullah
Benjamin
B
Neuenswander
Gerald H
GH
Lushington
Fatima Z
FZ
Basha
Michael G
MG
Organ
Paul R
PR
Hanson
D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry*; D044005:Tetrahydroisoquinolines / Q000737:chemistry*
D054852:Small Molecule Libraries; D013449:Sulfonamides; D044005:Tetrahydroisoquinolines; C480101:beta-sultam