Ginger (Zingiber officinale Roscoe) has been used as a spice and as a traditional remedy since ancient times, especially in traditional Chinese medicine. It has been applied as a treatment for many diseases either alone or in combination with other remedies. Many studies were conducted on ginger and its constituents and a wide array of bioactivities were reported, e.g., antioxidant, anti-inflammatory, antiemetic, and anticancer activity. Most of these had been correlated to gingerols and shogaols, the most abundant secondary metabolites in ginger. This inspired several research groups to explore the biomedical value of the chemical space around these compounds, and many of their synthetic or semi-synthetic analogues have been prepared and studied for various bioactivities. Thanks to this, many valuable structure activity relationships have been revealed for such compounds. Herein, we provide a brief summary on the synthetic derivatization efforts that had so far been implemented on 6-gingerol, the main constituent of fresh ginger. This review covers 160 natural, semisynthetic, or synthetic 6-gingerol derivatives and their reported bioactivities.

Ginger (Zingiber officinale) is widely used as a spice and a traditional medicine. Many bioactivities have been reported for its extracts and the isolated compounds, including cardiovascular protective effects. Different pathways were suggested to contribute to these effects, like the inhibition of platelet aggregation. In this study, we synthesised fourteen 6-gingerol derivatives, including eight new compounds, and studied their antiplatelet, COX-1 inhibitor, and antioxidant activities. In silico docking of selected compounds to h-COX-1 enzyme revealed favourable interactions. The investigated 6-gingerol derivatives were also characterised by in silico and experimental physicochemical and blood–brain barrier-related parameters for lead and preclinical candidate selection. 6-Shogaol (2) was identified as the best overall antiplatelet lead, along with compounds 3 and 11 and the new compound 17, which require formulation to optimize their water solubility. Compound 5 was identified as the most potent antioxidant that is also promising for use in the central nervous system (CNS).

Previously undescribed steroids vernomigeodiins A-D (1-4), were isolated from the African medicinal plant Vernoniastrum migeodii along with known sterols 5-10 and the tripeptide aurantiamide acetate (11). The isolated steroids featured a stigmastane skeleton with a unique conjugated Δ^7,9(11)-diene segment and a highly oxidized side chain, occasionally forming a bi- or tricyclic ring system. Sterols 1-3, 5-9 are glucosylated, whereas 4 and 10 are aglycons. The structures of the compounds were elucidated on the basis of 1D and 2D NMR spectroscopy and HRESIMS analyses. The isolated sterols were evaluated for their antiviral activities against Herpes simplex virus type 2. First, their cytotoxicity was assessed in Vero cells using the standard MTT assay, and direct quantitative PCR was then used to evaluate the antiviral activity. Vernomigeodiins A (1) and B (4) and vernonioside B₁ (6) were not cytotoxic up to a concentration of 10 μM but reduced the HSV-2 viral DNA levels with IC₅₀ values between 0.25 and 0.56 μM. In addition, vernoamyoside B (9) showed a direct virucidal effect (IC₅₀ = 1.23 ± 0.15 μM). The interactions between the antiviral compounds and specific viral targets were investigated using molecular docking.