Pharmacological Importance of Optically Active Tetrahydro-β-carbolines and Synthetic Approaches to Create the C1 Stereocenter

Abstract

1,2,3,4-Tetrahydro-β-carbolines (THβCs) are a pharmacologically important group of compounds belonging to the indole alkaloids. C1-Substituted optically active THβCs have been the target of extensive synthetic efforts due to the presence of the scaffold in numerous natural products and synthetic targets. This review briefly summarizes the methods to obtain the C1 stereocenter and concentrates on evaluating the pharmacological importance of optically active C1-substituted THβCs, including their PDE5-inhibitory, antimalarial, antiviral and antitumor activities.

Enantiospecific gram scale synthesis of (S)-eleagnine

“…(2) A, V¼3349.4(5) A 3 , Z¼4, r(calcd)¼1.179 Mg m À3 , F(000)¼1264, m¼0.077 mm À1 , 7656 reflections (2q max ¼55 ), 7656 unique [R int ¼0.000], 383 parameters, 1 restraints, R1 (for 6137 I>2s(I))¼ 0.049, wR2 (all data)¼0.105, S¼1.04, largest diff. peak and hole 0.208 and À0.148 e A À3 , x¼À0.0(10), y¼0.3 (5).…”

“…2e4 We have previously been interested in the synthesis of alkaloids of the tetrahydro-b-carboline (THbC) family (Fig. 1), a privileged structural family showcasing a rich array of bioactivities, 5,6 starting from amino acids, as an alternative to the standard Pictet-Spengler (PS) and Bischler-Napieralski (BN) approaches, by use of a Pf-protecting group strategy. 7e11 As an extension of this work we now wish to report a gram scale synthesis of the (S)-enantiomer of eleagnine, an alkaloid isolated from various plant sources, 12 originally isolated from Petalostyles labicheoides 13 and Elaeagnus angustifolia, 14 starting from L-alanine (Fig.…”

β-Carboline-functionalized dithioacetal as Hg2+-selective fluorescence probe in water

“…b-Carboline, with the common tricyclic pyrido [3,4-b]indole ring structure, has been widely used in the study of antitumor drugs [30][31][32][33]. It also has another merit, that of being a good luminophor, which derives from its aromatic planar configuration; however, this property has been largely ignored.…”

Synthesis and cytotoxicity of a novel series of saframycin-ecteinascidin analogs containing tetrahydro-β-carboline moieties

“…The tetrahydro-β-carboline (THβC) ring system occurred in many indole alkaloids and showed widespread biological properties [12]. Furthermore, the tetrahydro-β-carboline (THβC) and the tetrahydroisoquinoline (THIQ) share the similar chemical structure and biosynthetic pathway (the Pictet-Spengler reaction) [1,13].…”