Solution- and solid-phase, modular approaches for obtaining different natural product-like polycyclic architectures from an aminoindoline scaffold for combinatorial chemistry.
With the goal of developing a modular approach leading to different indoline alkaloid natural-product-like tricyclic derivatives having an unsaturated lactam (see compounds 13, 14, and 16), an aminoindoline-based bicyclic scaffold 10 was obtained from 9. The selective deprotection of the indoline NTeoc or benzylic NHAlloc in compound 10, followed by N-acryloylation and then subjection to a ring-closing metathesis reaction, successfully led to obtaining two different architectures (13/14 and 16) having an unsaturated lactam functionality. This modular solution-phase methodology was then developed on solid phase. To achieve this objective, the aminoindoline bicyclic scaffold having an additional hydroxyl group could be immobilized onto the solid support using alkylsilyl linker-based polystyrene macrobeads, giving 18. By applying a ring-closing metathesis approach, 20 (tricyclic derivative with seven-membered-ring unsaturated lactam) and 23 (tricyclic derivative with eight-membered-ring unsaturated lactam) were then obtained from 18 in a number of steps.
Reddy
P Thirupathi
PT
Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Ontario, Canada, K1A 0R6.
Quevillon
S
S
Gan
Zhonghong
Z
Forbes
Nauzer
N
Leek
Donald M
DM
Arya
Prabhat
P
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012680:Sensitivity and Specificity; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism
D007211:Indoles; D011083:Polycyclic Compounds; D012996:Solutions