Veratrum spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of Veratrum plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17–45 Veratrum spp., Veratrum californicum alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied V. californicum alkaloids are cyclopamine (1), veratramine (2), isorubijervine (3), muldamine (4), cycloposine (5), and veratrosine (6). Recent inspection of the ethanolic extract from V. californicum root and rhizome via liquid chromatography–mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine (7), etioline (8), tetrahydrojervine (9), dihydrojervine (10), 22-keto-26-aminocholesterol (11). For each alkaloid identified or proposed in V. californicum, this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.

4‐Oxo‐trans‐decahydrochinolin (I) kondensiert mit den Anilinen (II) in Hexan/Benzol unter Tos‐OH‐Katalyse zu den Iminen (III), die mit Hydrid überwiegend zu den axialen Aminen (IV) reduziert werden.

Titelverbindungen vom Typ (I)‐(IV) wurden nach Literatur‐Metho‐ den synthetisiert und auf ihre β‐ und /oder α‐antiadrenergischen Eigenschaften ‐ in Beziehung zu den Strukturen ‐ untersucht.

N‐Alkylierung des axialen trans‐4‐Hydroxy‐decahydrochinolins (I) mit den Aryloxypropylchloriden (II) gibt die Derivate (III), deren Chlorcarbonyloxy‐Derivate (IV) in situ mit den Aminen (V) zu den Carbamaten (VI) umgesetzt werden.

The native Idaho plant Veratrum californicum is known to contain steroidal alkaloids that function as inhibitors of hedgehog signaling, a pathway utilized for the growth and differentiation of cells as well as proper tissue development. Veratrum californicum was originally noticed when pregnant ewes consumed the plant and later gave birth to lambs with craniofacial mutations such as a cyclopean eyes. These malformations were caused by the plant’s steroidal alkaloid cyclopamine blocking the hedgehog signaling pathway. This same pathway is used by more than 20 types of cancer for multiplication of cells. Additional alkaloids have been found in Veratrum californicum, which are being studied in order to identify additional hedgehog signaling inhibitors. There are at least seven compounds detected in extracts that are completely uncharacterized, twelve with proposed identities, and the six known alkaloids veratrosine, cycloposine, veratramine, cyclopamine, isorubijervine, and muldamine all within Veratrum californicum. In this thesis these molecules were extracted together from the root and rhizome of the plant, and then separated into five fractions using high performance liquid chromatography. Mass spectrometry analysis identified the presence of twenty five alkaloids (nine more than literature precedent), and software processing of the data predicted the molecular formulas for each known, suspected, and unknown alkaloid. The bioactivity of the raw extract and each fraction was assessed by comparison to 0.1 μM cyclopamine, and it was found that three fractions suppressed hedgehog signaling to a greater extent, indicating the presence of bioactive constituents worthy of further investigation. Five fractions were collected at 2.5 min intervals, beginning at 10.25 min from time of raw extract injection. Fraction 1 was most potent at Hh signal inhibition, and was determined to contain veratrosine, cycloposine, and an isomer of each, followed by fractions 2 and 4, which possessed elevated bioactivity, but to a lesser extent than fraction 1. Fraction 2 was predicted to be comprised of cycloposine, its isomer, an isomer of veratrosine, tetrahydrojervine, veratramine, dihydrojervine, its isomer, etioline, and five unknown compounds. Fraction 4 was composed of cyclopamine, and suspected to contain isomers of veratramine and cyclopamine, isorubijervine, and muldamine, as well as two unknown alkaloids.