8
TÓTH ET AL.
2. Gosmini R, Nguyen VL, Toum J, et al. The discovery of I‐
BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1
up‐regulator and selective BET bromodomain inhibitor. J Med
Chem. 2014;57(19):8111‐8131.
Acetylcholinesterase inhibitory activity of the prod-
ucts was tested, and rac‐7 was found to show moderate
AChE inhibitory activity with 35.4% inhibition at 40‐μM
concentration. The neuroprotective activities of the prod-
ucts were also tested against hydrogen peroxide (H2O2),
β‐amyloid‐25‐35 fragment (Aβ25‐35), and oxygen‐glucose
deprivation‐induced neurotoxicity in human neuroblas-
toma SH‐SY5Y cells. The preliminary screenings showed
that rac‐3 at 1‐μM concentration displayed neuroprotec-
tive activity against oxygen‐glucose deprivation‐induced
cellular injuries in human neuroblastoma SH‐SY5Y cells
with 18.6% increase in cell viability.
3. Wang T, Zhuo L‐G, Li Z, et al. Highly enantioselective hydroge-
nation of quinolines using phosphine‐free chiral cationic
ruthenium catalysts: scope, mechanism, and origin of
enantioselectivity. J Am Chem Soc. 2011;133(25):9878‐9891.
4. Meth‐Cohn O. The t‐amino effect: heterocycles formed by ring
closure of ortho‐substituted t‐anilines. In: Katriczky AR, ed.
Advances in heterocyclic chemistry. San Diego: Academic Press,
Inc; 1996:1‐37.
5. Mátyus P, Eliás O, Tapolcsányi P, Polonka‐Bálint A, Halász‐
Dajka B. Ring‐closure reactions of ortho‐vinyl‐tert‐anilines and
(di)aza‐heterocyclic analogues via the tert‐amino effect: recent
developments. Synthesis. 2006;2006(16):2625‐2639.
4 | CONCLUSION
6. Groenen LC, Verboom W, Nijhuis WHN, Reinhoudt DN, Van
Hummel GJ, Feil D. The tertiary amino effect in heterocyclic
synthesis: mechanistic and computational study of the forma-
tion of six‐membered rings. Tetrahedron. 1988;44(14):4637‐4644.
Eight chiral hexahydropyrrolo[1,2‐a]quinoline derivatives
were prepared in a Knoevenagel‐[1,5]‐hydride shift‐
cyclization cascade reaction. The enantiomers of 1 to 8
could be separated by chiral HPLC whose absolute con-
figuration was determined by means of HPLC‐ECD and
TDDFT‐ECD calculations. The correlation of the absolute
configuration with ECD data for hexahydropyrrolo[1,2‐a]
7. Rabong C, Hametner C, Mereiter K, Kartsev VG, Jordis U. Scope
and limitations of the T‐reaction employing some functionalized
C‐H‐acids and naturally occurring secondary amines. Heterocy-
cles. 2008;75(4):799‐838.
8. Platonova AY, Poluikova AA, Glukhareva TV, Morzherin YY.
Synthesis of fused 3‐cyano‐ and 3‐carbamoyl‐1,2,3,4‐
tetrahydroquinolines. Russ Chem Bull. 2014;63(7):1580‐1583.
quinoline
derivatives
may
help
the
future
enantioselective version of the domino reaction. For the
product obtained with 2‐nitro‐1‐phenylethanone, not
only enantiomers but also diastereomers could be distin-
guished by ECD calculations aiding the assignment of
the relative configuration.
9. Pearson WH, Fang W. Synthesis of benzo‐fused 1‐azabicyclo[m.
n.0]alkanes via the Schmidt reaction: a formal synthesis of
gephyrotoxin. J Org Chem. 2000;65(21):7158‐7174.
10. Lee J, Ha JD, Cha JK. New synthetic method for functionalized
pyrrolizidine, indolizidine, and mitomycin alkaloids. J Am
Chem Soc. 1997;119(34):8127‐8128.
ACKNOWLEDGMENTS
The authors thank the National Research, Development
and Innovation Office (grant nos. NKFI K120181,
K112951, and PD121020) for financial support and the
CPU time by the Governmental Information‐Technology
Development Agency (KIFÜ). The computational stereo-
chemical studies of 5 were realized in the frames of
TÁMOP 4.2.4. A/2‐11‐1‐2012‐0001 National Excellence
Program—Elaborating and operating an inland student
and researcher personal support system convergence
program.
12. Grimme S. Semiempirical GGA‐type density functional con-
structed with a longrange dispersion correction. J Comput
Chem. 2006;27(15):1787‐1799.
13. Sun P, Xu DX, Mándi A, et al. Structure, absolute configuration,
and conformational study of 12‐membered macrolides from the
fungus Dendrodochium sp. associated with the sea cucumber
Holothuria nobilis Selenka. J Org Chem. 2013;78(14):7030‐7047.
14. Yanai T, Tew D, Handy N. A new hybrid exchange‐correlation
functional using the Coulomb‐attenuating method (CAM‐
B3LYP). Chem Phys Lett. 2004;393(1‐3):51‐57.
15. Pescitelli G, Bari DL, Berova N. Conformational aspects in the
studies of organic compounds by electronic circular dichroism.
Chem Soc Rev. 2011;40(9):4603‐4625.
ORCID
16. Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 09, Revision
B.01. Wallingford CT, Gaussian; 2010.
17. Stephens PJ, Harada N. ECD cotton effect approximated by
the Gaussian curve and other methods. Chirality. 2010;22(2):
229‐233.
REFERENCES
1. Sridharan V, Suryavanshi PA, Menendez JC. Advances in the
chemistry of tetrahydroquinolines. Chem Rev. 2011;111(11):
7157‐7259.
18. Varetto U. MOLEKEL, v. 5.4, Swiss National Supercomputing
Centre, Manno, Switzerland, 2009.