The modification of highly oxygenated forskolin as well as manoyl and epi-manoyl oxide, two less functionalized model substrates sharing the same polycyclic skeleton, via intermolecular carbon-centered radical addition to the vinyl moiety has been investigated. Highly regio- and reasonably stereoselective iodine atom transfer radical addition (ATRA) reactions were developed. Unprotected forskolin afforded an unexpected cyclic ether derivative. Protection of the 1,3-diol as an acetonide led the formation of the iodine ATRA product. Interestingly, by changing the mode of initiation of the radical process, in situ protection of the forskolin 1,3-diol moiety as a cyclic boronic ester took place during the iodine ATRA process without disruption of the radical chain process. This very mild radical-mediated in situ protection of 1,3-diol is expected to be of interest for a broad range of radical and non-radical transformations. Finally, by using our recently developed tert-butyl­catechol-mediated hydroalkylation procedure, highly efficient preparation of forskolin derivatives bearing an extra ester or sulfone group was achieved.

The bicyclic core of the halimanic framework is synthesized in optically active form by an acid-induced rearrangement of a homo­drimanic epoxide. The substrate can follow two different pathways under acidic treatment. Using fluorosulfonic acid as a promoter at low temperature favors ring contraction to a perhydrindanic structure. In contrast, milder acids at higher temperatures bring about predominantly an angular methyl migration and formation of the halimanic bicyclic system. In particular, an acidic pillared clay selectively promoted this transformation.

A convenient strategy for molecular editing of available ent-kauranic natural scaffolds has been developed based on radical mediated C–C bond formation. Iodine atom transfer radical addition (ATRA) followed by rapid ionic elimination and radical azidoalkylation were investigated. Both reactions involve radical addition to the exo-methylenic double bond of the parent substrate. Easy transformations of the obtained adducts lead to extended diterpenes of broad structural diversity and artificial diterpene-alkaloid hybrids possessing lactam and pyrrolidine pharmacophores. The cytotoxicity of selected diterpenic derivatives was examined by in vitro testing on several tumor cell lines. The terpene-alkaloid hybrids containing N-heterocycles with unprecedented spiro-junction have shown relevant cytotoxicity and promising selectivity indexes. These results represent a solid basis for following research on the synthesis of such derivatives based on available natural product templates.

Background/Objectives: Psoriasis is a chronic, recurrent inflammatory skin disorder with a steadily rising prevalence worldwide. Current therapeutic strategies include topical and systemic treatments selected based on disease severity and associated comorbidities; however, no therapy provided a definitive cure. Topical therapy is associated with a lower risk of systemic adverse effects, although the altered skin barrier observed in psoriasis may significantly reduce the bioavailability of active pharmaceutical ingredients. The aim of this study was to develop and evaluate the efficacy of a topical formulation containing triterpenoid acids derived from lavender extract (Lavandula angustifolia Mill.) as a potential adjunctive approach for symptom management in patients with psoriasis and chronic kidney disease (CKD). Methods: Following removal of the volatile oil, oleanolic, ursolic, pomolic, and rosmarinic acids were identified and quantified. The preparation was analyzed in terms of organoleptic properties, colloidal stability, pH determination, and rheological characteristics. The clinical study included 18 patients (both sexes) aged 28 to 71 years, with psoriasis and CKD of varying etiologies. Urinary albumin/creatinine ratio (uACR) and estimated glomerular filtration rate (eGFR) were used as renal biomarkers, while high-sensitive C-reactive protein (hs-CRP), hs-CRP/albumin, and neutrophil–lymphocyte ratio (NLR) were selected as inflammatory biomarkers. Laboratory assessments were performed at baseline and after 60 days of topical treatment with the lavender extract-based formulation. Clinical outcomes were evaluated using validated measures of psoriasis severity and patient impact, including the Psoriasis Area and Severity Index (PASI), the Investigator Global Assessment (IGA), and the Dermatology Life Quality Index (DLQI). Results: The formulation contained 1.4% rosmarinic acid and up to 8% ursolic acid (extract mass) and demonstrated good stability, a pH of 5.5, favorable local tolerability, antiproliferative activity, reduction in pruritus, and no treatment-related adverse effects. Efficacy and tolerability scores showed statistically significant improvements at 60 days (T2) after topical terpenoid administration compared with baseline (T0): PASI (0.722 ± 0.714 vs. 2.044 ± 0.690 at T0, p < 0.001), DLQI (3.889 ± 1.997 vs. 13.333 ± 3.361 at T0, p < 0.001), and IGA (0.556 ± 0.616 at T2 vs. 2.167 ± 0.618, p < 0.001). uACR decreased significantly over the study period (308.714 ± 240.782 after 60 days vs. 379.78 ± 308.81 at T0, p < 0.001), while eGFR values remained similar at baseline and follow-up. All evaluated inflammatory biomarkers showed significant reductions: hs-CRP (4.33 ± 2.127 at T2 vs. 9.7 ± 10.045 at T0, p < 0.009), hs-CRP/albumin ratio (0.105 ± 0.052 at T2 vs. 0.241 ± 0.225, p < 0.011), and NLR (2.154 ± 2.171 vs. 2.253 ± 0.256 at baseline, p = 0.027). Linear regression analysis identified no predictors of responsiveness to topical triterpenoid therapy in patients with psoriasis and CKD. Conclusions: This topical lavender extract-based formulation showed promising clinical and anti-inflammatory effects and favorable local tolerability in this pilot cohort of psoriasis patients with CKD. However, these findings should be considered preliminary and require confirmation in larger randomized controlled studies.