Stereodivergent synthesis of β-trifluoromethyl-α- amino acids by sequential catalytic processes

In this work, a sequential organocatalytic process for the stereodivergent synthesis of β-trifluoromethyl-α-amino acids using Erlenmeyer azlactones as starting material is presented. The strategy developed consists of a sequential catalytic approach, employing two catalysts that act independently to control the absolute configuration of two different stereocenters. The first step is a catalytic asymmetric hydrogen transfer of the activated double bond of the azlactone promoted by a Jacobsen type thiourea and Hantzsch ester as hydride donor. The second step involves a nucleophilic addition of an alcohol to the carbonyl moiety controlled by a chiral bifunctional catalyst typically used in the dynamic kinetic resolution of azlactones. The catalyst structure for the second synthetic step was thoroughly investigated in order to maximize the selectivity. Both products were achieved with a good diastereoselectivity and high enantioselectivity. Taking into account the obtained result it was possible to set up an initial study for the feasibility of straightforward one-pot procedure. In conclusion, with this work it was possible to set up a synthetic strategy for the synthesis of all four diastereoisomers starting from the set of starting material

Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone

Type I diabetes mellitus is caused by autoimmune destruction of pancreatic β cells, and effective treatment of the disease might require rescuing β cell function in a context of reinstalled immune tolerance. Sertoli cells (SCs) are found in the testes, where their main task is to provide local immunological protection and nourishment to developing germ cells. SCs engraft, self-protect, and coprotect allogeneic and xenogeneic grafts from immune destruction in different experimental settings. SCs have also been successfully implanted into the central nervous system to create a regulatory environment to the surrounding tissue which is trophic and counter-inflammatory. We report that isolated neonatal porcine SC, administered alone in highly biocompatible microcapsules, led to diabetes prevention and reversion in the respective 88 and 81% of overtly diabetic (nonobese diabetic [NOD]) mice, with no need for additional β cell or insulin therapy. The effect was associated with restoration of systemic immune tolerance and detection of functional pancreatic islets that consisted of glucose-responsive and insulin-secreting cells. Curative effects by SC were strictly dependent on efficient tryptophan metabolism in the xenografts, leading to TGF-β–dependent emergence of autoantigen-specific regulatory T cells and recovery of β cell function in the diabetic recipients

Front Cover: Adsorption of a Chiral Amine on Alginate Gel Beads and Evaluation of its Efficiency as Heterogeneous Enantioselective Catalyst (Eur. J. Org. Chem. 24/2019)

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