RASHID ET AL.
18. Bailey PD, Clingan PD, Mills TJ, Price RA, Pritchard RG. Total synthesis
sabbatical fellowship award of Higher Education Commission
(HEC), Pakistan for research in the University of Debrecen.
of (ꢁ)-raumacline. Chem Commun 2003;22:2800–2801.
19. Hino T, Nakagawa M. Total synthesis of fumitremorgins and verruculo-
gens. Heterocycles 1997;46:673–704.
20. Pictet A, Spengler T. Über die Bildung von Isochinolin-derivaten durch
Einwirkung von Methylal auf Phenyl-äthylamin, Phenyl-alanin und Tyrosin.
Ber Dtsch Chem Ges 1911;44:2030–2036.
LITERATURE CITED
1. Rabindran SK, He HY, Singh M, Brown E, Collins KI, Annable T,
Greenberger LM. Reversal of a novel multidrug resistance mechanism
in human colon carcinoma cells by fumitremorgin C. Cancer Res
1998;58:5850–5858.
2. He HY, Rabindran SG, Greenberger LM, Carter GT. Fumitremorgin C
analogs that reverse mitoxantrone resistance in human colon carcinoma
cells. Med Chem Res 1999;9:424–437.
3. Sunder-Plassmann N, Sarli V, Gartner M, Utz M, Seiler J, Huemmer S,
Mayer TU, Surrey T, Giannis A. Synthesis and biological evaluation of
new tetrahydro-beta-carbolines as inhibitors of the mitotic kinesin Eg5.
Bioorg Med Chem 2005;13:6094–6111.
4. Gupta L, Srivastava K, Singh S, Puri SK, Chauhan PMS. Synthesis of 2-[3-
(7-Chloro-quinolin-4-ylamino)-alkyl]-1-(substituted phenyl)-2,3,4,9-tetrahydro-
1H-beta-carbolines as a new class of antimalarial agents. Bioorg Med Chem
Lett 2008;18:3306–3309.
21. Royer J, Bonin M, Micouin L. Chiral heterocycles by iminium ion cycliza-
tion. Chem Rev 2004;104:2311–2352.
22. Cox ED, Cook JM. The Pictet-Spengler Condensation: A New Direction
for an Old Reaction. Chem Rev 1995;95:1797.
23. Stöckigt J, Antonchick AP, Wu F, Waldmann H. The Pictet–Spengler
Reaction in Nature and in Organic Chemistry. Angew Chem Int Ed
2011;50:8538.
24. Szabó LF. Rigorous biogenetic network for a group of indole alkaloids
derived from strictosidine. Molecules 2008;13:1875–1896.
25. Stöckigt J, Zenk MH. Strictosidine (Isovincoside) - Key Intermediate
in Biosynthesis of Monoterpenoid Indole Alkaloids. J Chem Soc Chem
Commun 1977;18:646–648.
26. Bailey PD, Hollinshead SP, McLay NR, Morgan K, Palmer SJ, Prince SN,
Reynolds CD, Wood SD. Diastereoselectivity and Enantioselectivity in the
Pictet-Spengler Reaction. J Chem Soc Perkin Trans 1 1993;3:431–439.
27. Maresh JJ, Giddings LA, Friedrich A, Loris EA, Panjikar S, Trout BL,
Stöckigt J, Peters B, O’Connor SE. Strictosidine synthase: Mechanism
of a Pictet-Spengler catalyzing enzyme. J Am Chem Soc 2008;130:710–723.
28. Xiao S, Lu X, Shi XX, Sun Y, Liang LL, Yu XH, Dong J. Syntheses of
chiral 1,3-disubstituted tetrahydro-beta-carbolines via CIAT process:
highly stereoselective Pictet-Spengler reaction of D-tryptophan ester
hydrochlorides with various aldehydes. Tetrahedron: Asymmetry
2009;20:430–439.
29. Soerens D, Sandrin J, Ungemach F, Mokry P, Wu GS, Yamanaka E,
Hutchins L, DiPierro M, Cook JM. Study of the Pictet-Spengler Reaction in
Aprotic Media - Synthesis of the Beta-Galactosidase Inhibitor, Pyridindolol.
J Org Chem 1979;44:535–545.
30. Alberch L, Bailey PD, Clingan PD, Mills TJ, Price RA, Pritchard RG. The
cis-specific Pictet-Spengler reaction. Eur J Org Chem 2004;1887–1890.
31. Bailey PD, Beard MA, Phillips TR. Unexpected cis selectivity in the Pictet-
5. Bi W, Cai J, Liu S, Baudy-Floc’h M, Bi LR. Design, synthesis and cardio-
protective effect of a new class of dual-acting agents: Phenolic tetrahydro-
beta-carboline RGD peptidomimetic conjugates. Bioorg Med Chem
2007;15:6909–6919.
6. Tonin LTD, Barbosa VA, Bocca CC, Ramos ERF, Nakamura CV, da Costa
WF, Basso EA, Nakamura TU, Sarragiotto MH. Comparative study of the
trypanocidal activity of the methyl 1-nitrophenyl-1,2,3,4-9H-tetrahydro-
beta-carboline-3-carboxylate derivatives and benznidazole using theoretical
calculations and cyclic voltammetry. Eur J Med Chem 2009;44:1745–1750.
7. Srivastava SK, Agarwal A, Chauhan PMS, Agarwal SK, Bhaduri AP, Singh
SN, Fatima N, Chatterjee RK. Potent 1,3-disubstituted-9H-pyrido[3,4-b]
indoles as new lead compounds in antifilarial chemotherapy. J Med Chem
1999;42:1667–1672.
8. Srivastava SK, Agarwal A, Chauhan PMS, Agarwal SK, Bhaduri AP, Singh
SN, Fatima N, Chatterjee RK. Potent 1,3-disubstituted-9H-pyrido[3,4-b]
indoles as new lead compounds in antifilarial chemotherapy. Bioorg
Med Chem 1999;7:1223–1236.
Spengler reaction. Tetrahedron Lett 2009;50:3645–3647.
9. Riederer P, Foley P, Bringmann G, Feineis D, Bruckner R, Gerlach M.
Biochemical and pharmacological characterization of 1-trichloromethyl-1,
2,3,4-tetrahydro-beta-carboline: a biologically relevant neurotoxin? Eur
J Pharmacol 2002;442:1–16.
32. Saha B, Sharma S, Sawant D, Kundu B. Water as an efficient medium for
the synthesis of tetrahydro-beta-carbolines via Pictet-Spengler reactions.
Tetrahedron Lett 2007;48:1379–1383.
33. Yen YH, Chu YH. Synthesis of tetrahydro-beta-carbolinediketopiperazines
in [bdmim][PF6] ionic liquid accelerated by controlled microwave heating.
Tetrahedron Lett 2004;45:8137–8140.
34. Kuo FM, Tseng MC, Yen YH, Chu YH. Microwave accelerated
Pictet-Spengler reactions of tryptophan with ketones directed toward
the preparation of 1,1-disubstituted indole alkaloids. Tetrahedron
2004;60:12075–12084.
10. Trujillo JI, Meyers MJ, Anderson DR, Hegde S, Mahoney MW, Vernier WF,
Buchler IP, Wu KK, Yang SL, Hartmann L, Reitz DB. Novel tetrahydro-
beta-carboline-1-carboxylic acids as inhibitors of mitogen activated
protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem Lett
2007;17:4657–4663.
11. Daugan A, Grondin P, Ruault C, Le Monier de Gourville AC, Coste H,
Linget JM, Kirilovsky J, Hyafil F, Labaudinière R. The discovery of
tadalafil: A novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-
hexahydropyrazino[1 ′,2 ′: 1,6]pyrido[3,4-b]indole-1,4-dione analogues.
J Med Chem 2003;46:4533–4542.
35. Peng SQ, Guo M, Winterfeldt E. Synthesis of Enantiomerically Pure
Tetrahydro-2-Methylharman. Liebigs Ann Chem 1993;137–140.
36. Ungemach F, Soerens D, Weber R, Dipierro M, Campos O, Mokry P,
Cook JM, Silverton JV. General-method for the assignment of stereo-
chemistry of 1,3-disubstituted 1,2,3,4-tetrahydro-beta-carbolines by C-13
spectroscopy. J Am Chem Soc 1980;102:6976–6984.
12. Maw GN, Allerton CMN, Gbekor E, Million WA. Design, synthesis and
biological activity of beta-carboline-based type-5 phosphodiesterase inhibi-
tors. Bioorg Med Chem Lett 2003;13:1425–1428.
13. Yu X, Lin W, Li J, Yang M. Synthesis and biological evaluation of novel
beta-carboline derivatives as Tat-TAR interaction inhibitors. Bioorg Med
Chem Lett 2004;14:3127–3130.
14. Formagio ASN, Tonin LTD, Foglio MA, Madjarof C, de Carvalho JE, da
Costa WF, Cardoso FP, Sarragiotto MH. Synthesis and antitumoral activity
of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-
3-yl) beta-carboline derivatives. Bioorg Med Chem 2008;16:9660–9667.
37. Yokoya M, Masubuchi K, Kitajima M, Takayama H, Aimi N. Synthesis
and CD measurement of chiral 1-ethyl-3-carboxy-1,2,3,4-tetrahydro-beta-
carbolines: C1 configuration and second sphere chirality. Heterocycles
2003;59:521–526.
38. Bringmann G, Feineis D, God R, Maksimenka K, Mühlbach J, Messer K,
Münchbach M, Gulden KP, Peters EM, Peters K. Resolution and
chiroptical properties of the neurotoxin 1-trichloromethyl-1,2,3,4-
tetrahydro-beta-carboline (TaClo) and related compounds: quantum
chemical CD calculations and X-ray diffraction analysis. Tetrahedron
2004;60:8143–8151.
15. Kawasaki T, Higuchi K. Simple indole alkaloids and those with a non-
rearranged monoterpenoid unit. Nat Prod Rep 2005;22:761–793.
16. Li J, Cook JM. General approach to the synthesis of sarpagine and
ajmaline alkaloids. Enantiospecific total synthesis of (+)-ajmaline and
alkaloid G via the asymmetric Pictet-Spengler reaction. J Org Chem
1998;63:4166–4167.
39. Tóth G, Szántay C, Kalaus G, Thaler G, Snatzke G. Stereochemistry of
1,2,3-trisubstituted tetrahydro-beta-carbolines. J Chem Soc Perkin Trans
2 1989;1849–1853.
40. Brossi A, Focella A, Teitel S. Alkaloids in mammalian tissues. 3. Conden-
sation of L-tryptophan and L-5-hydroxytryptophan with formaldehyde and
acetaldehyde. J Med Chem 1973;16:418.
41. Jacobs WA, Craig LC. The ergot alkaloid VIII. The Synthesis of 4-carbo-
line carbonic acids. J Biol Chem 1936;113:759.
17. Li J, Wang T, Yu P, Peterson A, Weber R, Soerens D, Grubisha D, Bennett
D, Cook JM. General approach for the synthesis of ajmaline/sarpagine
indole alkaloids: Enantiospecific total synthesis of (+)-ajmaline, alkaloid
G, and norsuaveoline via the asymmetric Pictet-Spengler reaction. J Am
Chem Soc 1999;121:6998–7010.
Chirality DOI 10.1002/chir