PhD Project - PhD in Chemistry: Sustainable Main Group Catalysis Using Frustrated Lewis Pairs at Cardiff University, listed on FindAPhD.com

Traditionally, a retrosynthesis aims to disconnect a molecular target into simpler precursors as quickly as possible, prioritizing the early deconstruction of primary contributors to the molecule’s overall structural complexity (i.e., primary complexity elements). The complementary approach, which rapidly constructs complexity early in the forward synthesis, is much less common. Herein, we report a 14-step protective group-free total synthesis of the polycyclic sesquiterpenoid alkaloid hispidospermidin, which exploits an early-stage complexity-generating bicycle formation to forge the carbon skeleton, followed by subsequent peripheral functionalizations. Specifically, a key Giese conjugate addition of a bridgehead radical established the quaternary center, and a novel isomerization was discovered, which enabled a one-pot protocol to establish the trans-hydrindane moiety, and application of a C–H desaturation/etherification sequence constructed the tetrahydrofuran moiety at a late stage. Uniquely, our strategy generates the primary complexity element, the bicyclo[3.3.1]nonane core, in the first step of the synthesis, whereas the three previous syntheses feature mid- to late-stage bicycle construction (total of 23–31 steps). Analysis of the structural complexity landscape of the four syntheses of hispidospermidin suggests that building a molecule from the “Inside-Out”, as described here, may be a broadly applicable strategy to expedite the total synthesis of topologically complex molecules.

Over the past decade, the synthesis of alkynyl sulfones and alkynyl chalcogen derivatives has witnessed significant advances. Modern methodologies have increasingly focused on sustainable protocols, c...

Upon catalysis (1 mol %) by a chiral cobalt porphyrin, quinazolinones with a tethered diazo alkane precursor underwent an enantioselective C–H alkylation at carbon atom C4. Formation of five-, six-, a...

We are delighted to kick off 2026 by welcoming Dr. Philipp Schoch as a new postdoctoral researcher in our team! Philipp joins us from the University of Konstanz, and we’re excited to have him on board...

Iron’s abundance motivates its use in sustainable catalyst systems that also offer complementary reactivity manifolds compared to precious metals. However, the challenging reduction of benchmark iron ...

A full year of total synthesis, retrosynthesis, and mechanistic problems! 🧪 With 20 new additions this year, the #LCSOSynthesisProblem collection has reached a milestone of 200+ exercises! Explore al...

Peptide drugs are a powerful modality in modern drug discovery. Synthetic methods that enable the late-stage diversification of native peptides through amino acid-specific modifications are thus in high demand. In this work, we demonstrate the epimerization-free, chemoselective late-stage diversification of tryptophan-containing native peptides through nitrogen atom insertion in solution. The direct application of this rapid and straightforward method to structurally complex peptide drugs underscores the broader potential of atom insertion reactions in drug discovery beyond small molecules.

Last week on the #LCSOSynthesisProblem, Valentas challenged us to the total synthesis of Glycinoeclepin A by Hu and co-workers. 💡 Want to challenge yourself or your team with this synthesis problem? ...

PhD Project - PhD in Chemistry: Single or Double? A Radical Approach to Catalysis - Competitive EPSRC funded post at Cardiff University, listed on FindAPhD.com

Last week, LCSO gathered for our annual Christmas dinner!🧀 We shared a delicious raclette, put our teamwork (and competitive spirit!) to the test with a fun quiz, and wrapped up the night with the ver...