## 3 Alkaloids
### Indole Alkaloids
#### 3.1.3. \(\beta\)-Carboline Alkaloids  
Indole alkaloids possessing the \(\beta\)-carboline subclass have been more recently isolated from _U. tomentosa_, with the first study identifying and structurally determining their presence in plant extracts established by [PERSON] and colleagues in 2000 [4, 5]. This group of indole alkaloids have a tricyclic structure highlighted in blue in Figure 2. This characteristic scaffolding is composed of an indole structure fused to a pyridine ring, where primary structural differences within the subclass arise from the saturation of this pyridine-type ring. In all cases, a carbon skeleton branches from C-3.  
The simplest of these alkaloids found in _U. tomentosa_ is harman (**10**). This molecule represents the core scaffolding of the \(\beta\)-carboline alkaloid subclass, with a fully aromatic ring system and a simple methyl substitution at C-3. Compound **10** was first isolated by [PERSON] and colleagues along with other \(\beta\)-carboline structures **11**, **12**, and **13**[4]. Compound **10** has demonstrated antibacterial activity against both Gram-negative and Gram-positive bacteria, exhibiting minimum inhibitory concentration (MIC) values of 500 \(\upmu\)g/mL against _Escherichia coli_ and _Bacillus subtilis_, and 1000 \(\upmu\)g/mL for _Staphylococcus aureus_[52]. Compound **10** has also been utilized as a scaffold for the development of antibacterial candidates, with some analogues exhibiting MIC values below 10 \(\upmu\)g/mL for _S. aureus_, methicillin-resistant _Staphylococcus aureus_ (MRSA), _B. cereus_, _B. subtilis_, and _Ralstonia solanacearum_[53]. Substitutions of the harman structure that improve antibacterial activity include substituting C-6 with a hemoz[d][1,3]dioxE group, and the quaternization of N-2 with a _para_-substituted benzyl group and a complexed bromine anion [53].  
The gluco-\(\beta\)-carboline-type alkaloids **11-13** were also isolated by [PERSON] and colleagues in a previous study [5]. The structures were determined utilizing UV, \({}^{1}\)H and \({}^{13}\)C NMR spectroscopy, and MS, with the absolute configuration of compound **12** solved through a total synthesis based upon the biosynthetic precursors _L_-tryptophan and secologanin [4, 5, 7]. Compounds **12** and **13** differ only by the bond between C-3 and N-4, which is saturated in **13** and unsaturated in **12**. The saturation of this bond produces a stereocenter at C-3 for **13**, in the \(S\) configuration. Compound **11** possesses both the same skeletal structure and \(\beta\)-linked glucose molecule as **12** and **13**, with the fully conjugated \(\beta\)-carboline core, but lacks the carboxylic acid.  
There is only one study confirming the isolation of an additional glycosylated \(\beta\)-carboline alkaloid **14** from micropropagated plantlets and root cultures [50]. This structure possesses some unique features, including a methyl-substituted nitrogen and a stereocenter at C-3 in the \(S\) configuration. The glycosyl portion of the molecule is identical to that of compounds **11-13**. Compound **14** and a derivative of compound **13** have been identified as precursor molecules in the biosynthesis of tetracycline indolequinolizidine and pentacyclic indolequinolizidine alkaloids [47]. Antibacterial activity has been noted for compound **13**. When isolated from _Psychotria nuda_ ([PERSON] and Schltdl.) Wawra, **13** exhibited in vitro antimycobacterial activity against _Mycobacterium tuberculosis_ strain H37 Rv with a reported MIC value of 26.3 \(\upmu\)g/mL [54].