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Abstract A total synthesis of balgacyclamide A was reported for the first time in 2020, however, after multiple epimerization studies of β‐hydroxy amides dehydrative cyclization to access oxazolines, we proposed a configurational reassignment from the previous synthetic pathway. Balgacyclamide A is a macrocyclic hexapeptide with antiparasitic activity againstPlasmodium falciparumandTrypanosoma brucei rhodesiense. Chemically, its core contains six amino acids that undergo heterocyclization to form one thiazole and two oxazoline rings. Two of the six amino acids areL‐threonines that play an important role in their synthetic pathway to achieve oxazolines with the right configuration upon epimerization at the β‐carbon. Thus, we investigated the effect ofL‐threonine andL‐allothreonine β‐carbon epimerization via the Burgess reagent, diethylaminosulfur trifluoride (DAST), and (NH₄)₆Mo₇O₂₄•4H₂O catalyst to support previous oxazoline synthetic studies. Furthermore, the first total synthesis of balgacyclamide A and an epimer is reported via multiple synthetic key steps that involve a tandem sulfur incorporation, cyclization, and aromatization of the thiazole, and a late‐stage β‐hydroxy amide Walden inversion to access both oxazolines. 

Balgacyclamide A−C are a family of cyanobactin natural products isolated from freshwater cyanobacteriaMicrocystis aeruginosa. These macrocyclic peptides are characterized by their oxazoline‐thiazole core, their 7 or 8 stereocenters, and their antiparasitic activities. Balgacyclamide B is known for its activity towardsPlasmodium falciparumchloroquine‐resistant strain K1,Trypanosoma brucei rhodesiense, andLeishmania donovani. In this report, the first total synthesis of Balgacyclamide B is described in a 17‐steps pathway and a 2 % overall yield. The synthetic pathway toward balgacyclamide B can be adapted for the future syntheses of balgacyclamide A and C. In addition, a brief history background of oxazolines syntheses is shown to emphasize the importance of the cyclization conditions used to interconvert or retain configuration of β‐hydroxy amides via dehydrative cyclization. 

The synthesis of a new Nile red derivative incorporating a reactive aldehyde moiety (NR-CHO) is reported and its use in spectroscopic studies of heterogeneous catalyst activity in crossed aldol reactions is demonstrated. 1 H and 13 C NMR, and high-resolution mass spectrometry confirmed the desired NR-CHO was obtained. Mg-Zr-Cs doped silica (Cs(Zr,Mg)-SiO 2 ) was employed as the catalyst and its performance was compared to that of commercially available MgO. Fumed silica was used as a control. Aldol reactions with acetone and acetophenone were run in 4 : 1 (v/v) DMSO : ketone solutions in the presence of both dilute (1 μM) and concentrated (1 mM) NR-CHO. NR-CHO fluorescence spectra were acquired as the reactions progressed. Shifts in its emission spectrum are used to distinguish the products formed and to characterize the reaction rate. The dye exhibits different behavior that defines whether the reaction stops at the addition (alcohol) product, or forms both addition and condensation (olefin) products, providing valuable initial information on catalyst activity. The assignment of addition and condensation products is supported by thin layer chromatography, high performance liquid chromatography (HPLC), and HPLC-mass spectrometry data. Product formation is shown to depend upon the catalyst employed, with the Cs(Zr,Mg)-SiO 2 yielding both addition and condensation products, while MgO yields primarily addition products. The advantages of NR-CHO in spectroscopic studies of aldol reactions are also demonstrated relative to commercially available 3-perylenecarboxaldehyde. The NR-CHO reported here and the results obtained will facilitate a broad range of both ensemble and single molecule spectroscopic investigations of heterogeneous catalysis in crossed aldol reactions in the future.