Progress Towards the Syntheses of Ortho-Farnesylated Phenolic Natural Products
Bibliographic record
Abstract
Natural products have been an important part of medicine for centuries, starting from traditional medicines and remaining significant in drug discovery today. This thesis will focus on ortho-farnesylated phenolic natural products. Chapter 1 is a comprehensive review of the literature concerning ortho-farnesylated phenolic natural products, their natural occurrence, biosynthesis, bioactive properties, and methodologies toward their de novo synthesis. Chapter 2 showcases the first total synthesis of isoindolinone natural product chartarutine B which was isolated from the fungi Stachybotrys chartarum and shown to have moderate anti-HIV bioactivity. The four-step synthetic route features the use of a cobalt-catalyzed C(sp2)-H carbonylation and novel regioselective alumina-templated phenol ortho-farnesylation developed by the Magolan group. Chapter 3 focuses on the progress towards the first total syntheses of highly substituted phenolic natural products tuaimenal A and H, which were isolated from the deep-sea sponge Duva florida. Both compounds are modestly cytotoxic to two cervical cancer cell lines (EC50 46 μM, 23 μM; CaSki). Additionally, tuaimenal A is a viral protease inhibitor (EC50 21 μM; SARS-CoV-2 3CLpro). The synthetic route includes another application of the Magolan group ortho-farnesylation chemistry. Chapter 4 describes the synthesis of a library of structural analogues of lead compound NP-BTA, a potent inhibitor of Gln4 in the fungal pathogen Candida albicans that was conducted in collaboration with the laboratory of Prof. Leah Cowen at the University of Toronto. In this chapter, the structure-activity relationship study is summarized, and all details of the synthetic chemistry involved in this collaborative project are reported.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".