Deamination of 1-Aminoalkylphosphonic Acids: Reaction Intermediates and Selectivity.

Deamination of 1-aminoalkylphosphonic acids in the reaction with HNO2 (generated "in situ" from NaNO2) yields a mixture of substitution products (1-hydroxyalkylphosphonic acids), elimination products (vinylphosphonic acid derivatives), rearrangement and substitution products (2-hydroxylkylphosphonic acids) as well as H3PO4. The variety of formed reaction products suggests that 1-phosphonoalkylium ions may be intermediates in such deamination reactions.

Synthesis and stability of 1-aminoalkylphosphonic acid quaternary ammonium salts.

An effective protocol for the quaternization of simple 1-aminoalkylphosphonic acids under basic conditions using Me2SO4 as a convenient alkylating agent is reported. During the course of the reaction, phosphonic acid quaternary ammonium derivatives, along with their corresponding monoesters are formed. Subsequent direct acidic hydrolysis of the crude reaction mixture leads to the desired novel N,N,N-trialkyl-N-(1-phosphonoalkyl)ammonium salts with overall yields of up to 88%. The developed protocol is general in scope and the products are purified by simple crystallization to give stable solids. Novel quaternary ammonium salts bearing a phosphonic group are generally unreactive in acidic and alkaline media. However, some of them undergo Hofmann elimination and substitution reactions in the presence of a base.

The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm.

Prediction errors are thought to drive associative fear learning. Surprisingly little is known about the possible contribution of the cerebellum. To address this question, healthy participants underwent a differential fear conditioning paradigm during 7T magnetic resonance imaging. An event-related design allowed us to separate cerebellar fMRI signals related to the visual conditioned stimulus (CS) from signals related to the subsequent unconditioned stimulus (US; an aversive electric shock). We found significant activation of cerebellar lobules Crus I and VI bilaterally related to the CS+ compared to the CS-. Most importantly, significant activation of lobules Crus I and VI was also present during the unexpected omission of the US in unreinforced CS+ acquisition trials. This activation disappeared during extinction when US omission became expected. These findings provide evidence that the cerebellum has to be added to the neural network processing predictions and prediction errors in the emotional domain.

Aminophosphonates and aminophosphonic acids with tetrasubstituted stereogenic center: diastereoselective synthesis from cyclic ketimines.

New chiral tetrasubstituted aminophosphonic acid derivatives of hexahydroquinoxalin-2(1H)-one were synthesised via highly diastereoselective hydrophosphonylation of the corresponding imines with tris(trimethylsilyl) phosphite as phosphorus nucleophile. High asymmetric induction, good yields, mild reaction conditions, and ease of purification of the final products are the key advantages of the presented protocol.