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We report an intramolecular conjugate addition/Truce‐Smiles/E1cb cascade of 2‐nitrobenzenesulfonamide‐functionalized cyclohexenones as a new entry to the core scaffold of monoterpene indole alkaloids. The method was applied to the asymmetric total synthesis of (−)‐limaspermidine, (−)‐kopsinilam, and (−)‐kopsinine, as well as the framework of the kopsifoline alkaloids, thus highlighting its complementarity to existing approaches involving the use of indole‐based starting materials or the interrupted Fischer indole synthesis. Furthermore, we show that the cascade tolerates various substituents on the nitroarene, opening the way to other natural products as well as non‐natural analogues.

The common para regioselectivity in Pictet–Spengler reactions with dopamine derivatives is redirected to the ortho position by a simple change of solvents. In combination with a chiral auxiliary on nitrogen, this ortho-selective Pictet–Spengler produced the 1-benzyltetrahydroisoquinoline alkaloids (S)-crassifoline and (S)-norcrassifoline and the bioactive 1,2-dioxygenated tetrahydroprotoberberine alkaloids (S)-govaniadine, (S)-caseamine, and (S)-clarkeanidine with high enantiopurity. Ortho/para ratios up to 89:19 and diastereomeric ratios up to 85:15 were obtained during formation of the B-ring. The general applicability of this solvent-directed regioselectivity was demonstrated with a second Pictet–Spengler reaction as required for C-ring formation of caseamine (o/p = 14:86 in trifluoroethanol) and clarkeanidine (o/p = 86:14 in toluene).

We report a new synthesis of the Covid-19 drug nirmatrelvir featuring a highly enantioselective biocatalytic desymmetrization and a diastereoselective multicomponent reaction as the key steps. Our route avoids the use of transition metals and peptide coupling reagents, resulting in an overall highly atom-economic process.

Background This study aimed to compare laparoscopic lavage and sigmoidectomy as treatment for perforated diverticulitis with purulent peritonitis during a 36 month follow-up of the LOLA trial. Methods Within the LOLA arm of the international, multicentre LADIES trial, patients with perforated diverticulitis with purulent peritonitis were randomised between laparoscopic lavage and sigmoidectomy. Outcomes were collected up to 36 months. The primary outcome of the present study was cumulative morbidity and mortality. Secondary outcomes included reoperations (including stoma reversals), stoma rates, and sigmoidectomy rates in the lavage group. Results Long-term follow-up was recorded in 77 of the 88 originally included patients, 39 were randomised to sigmoidectomy (51%) and 38 to laparoscopic lavage (49%). After 36 months, overall cumulative morbidity (sigmoidectomy 28/39 (72%) versus lavage 32/38 (84%), p = 0·272) and mortality (sigmoidectomy 7/39 (18%) versus lavage 6/38 (16%), p = 1·000) did not differ. The number of patients who underwent a reoperation was significantly lower for lavage compared to sigmoidectomy (sigmoidectomy 27/39 (69%) versus lavage 17/38 (45%), p = 0·039). After 36 months, patients alive with stoma in situ was lower in the lavage group (proportion calculated from the Kaplan–Meier life table, sigmoidectomy 17% vs lavage 11%, log-rank p = 0·0268). Eventually, 17 of 38 (45%) patients allocated to lavage underwent sigmoidectomy. Conclusion Long-term outcomes showed that laparoscopic lavage was associated with less patients who underwent reoperations and lower stoma rates in patients alive after 36 months compared to sigmoidectomy. No differences were found in terms of cumulative morbidity or mortality. Patient selection should be improved to reduce risk for short-term complications after which lavage could still be a valuable treatment option. Graphical abstract