Synthesis of 2,3-Benzobicyclo[3.3.1]non-2-enes via a Cascade of Domino Carbocation Migration/Interrupted Ritter Reaction and Dienone-Phenol Rearrangement.

The 2,3-benzobicyclo[3.3.1]non-2-ene scaffold is a bridged backbone of many bioactive natural products.

Reconstituted CD74 NK cells trigger chronic graft versus host disease after allogeneic bone marrow transplantation.

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients with pulmonary cGVHD in particular have a very poor prognosis. NK cells are the first reconstituted lymphocyte subset after allo-HSCT; however, the impact of reconstituted NK cells on cGVHD is unclear.

Oxidative Dehydroxycyclization of Catechols with -Mercaptoanilines to Access 1-Hydroxyphenothiazines.

The protocol of aerobic oxidative dehydroxycyclization installed in the synthesis of rarely studied 1-hydroxyphenothiazines from catechols and -mercaptoanilines is presented. Utilizing a natural renewable low-toxicity gallic acid as an organocatalyst, this established transformation proceeded smoothly in an aqueous ethanol solution under mild conditions with good functional group compatibility and up to a 94% isolated yield. This protocol is also characterized by its operational simple workup involving only recrystallization, revealing its sustainability and synthetic practicability.

Total Synthesis of Ophiorrhine A, G and Ophiorrhiside E Featuring a Bioinspired Intramolecular Diels-Alder Cycloaddition.

We report the first total synthesis of the monoterpene indole alkaloids ophiorrhine A via a late stage bioinspired intramolecular Diels-Alder cycloaddition to form the intricate bridged and spirannic polycyclic system. Several strategies were investigated to construct the indolopyridone moiety of ophiorrhiside E, the postulated biosynthetic precursor of ophiorrhine A. Eventually, the Friedel-Crafts-type coupling of N-methyl indolyl-acetamide with a secologanin-derived acid chloride delivered ophiorrhine G.

Pictet-Spengler Reaction for the Chemical Synthesis of Strictosidine.

Strictosidine is the common biosynthetic precursor of Monoterpene Indole Alkaloids (MIA). A practical single-step procedure to assemble strictosidine from secologanin is described via a bioinspired Pictet-Spengler reaction. Mild conditions and purification by crystallization and flash chromatography allow access to the targeted product in fair yield.

Facile and scalable synthesis of baphicacanthin A by a two-pot procedure.

Facile two-pot total synthesis of baphicacanthin A, a natural phenoxazinone alkaloid isolated from the roots of which has been utilized as a traditional chinese medicine to effectively treat disease caused by coronavirus, has been developed from simple and commercially available starting materials. Catalytic aerobic oxidative cross-cyclocondensation of equimolar 2-aminophenol and 3-methoxy-2-hydroxylphenol in water was used to construct the key molecular skeleton 2-hydroxy-3-phenoxazin-3-one. Gram scale synthesis was realized in 80% overall yield with practical convenience.

Rapamycin Pretreatment Rescues the Bone Marrow AML Cell Elimination Capacity of CAR-T Cells.

Purpose: Ongoing clinical trials show limited efficacy for Chimeric antigen receptor (CAR) T treatment for acute myeloid leukemia (AML). The aim of this study was to identify potential causes of the reported limited efficacy from CAR-T therapies against AML.

Experimental Design: We generated CAR-T cells targeting Epithelial cell adhesion molecule (EpCAM) and evaluated their killing activity against AML cells.

Bioinspired Divergent Oxidative Cyclization from Strictosidine and Vincoside Derivatives: Second-Generation Total Synthesis of (-)-Cymoside and Access to an Original Hexacyclic-Fused Furo[3,2-b]indoline.

The second-generation synthesis of (-)-cymoside as well as the formation of a new hexacyclic-fused furo[3,2-b]indoline framework is reported. After a Pictet-Spengler condensation between secologanin tetraacetate and tryptamine, the course of the cyclization of the 7-hydroxyindolenine intermediate, generated by oxidation with an oxaziridine, depended on the stereochemistry of the 3-position. The 3-(S)-strictosidine stereochemistry delivered efficiently the scaffold of cymoside via intramolecular coupling with the C16-C17 enol ether, while the 3-(R)-vincoside stereochemistry directed towards the reaction with the C18-C19 terminal alkene and the formation of the unexpected caged compound.

Enantioselective Total Synthesis of Cymoside through a Bioinspired Oxidative Cyclization of a Strictosidine Derivative.

The first total synthesis of the caged monoterpene indole alkaloid cymoside is reported. This natural product displays a unique hexacyclic-fused skeleton whose biosynthesis implies an early oxidative cyclization of strictosidine. Our approach to the furo[3,2-b]indoline framework relied on an unprecedented biomimetic sequence which started by the diastereoselective oxidation of the indole ring into a hydroxyindolenine which triggered the addition of an enol ether and was followed by the trapping of an oxocarbenium intermediate.

Electrochemical Dearomative 2,3-Difunctionalization of Indoles.

We report the use of electrochemistry to perform a direct oxidative dearomatization of indoles leading to 2,3-dialkoxy or 2,3-diazido indolines under undivided conditions at a constant current. This operationally simple electro-oxidative procedure avoids the use of an external oxidant and displays excellent functional group compatibility. The formation of the two C-O or C-N bonds is believed to arise from the oxidation of the indoles into radical cation intermediates.