Yu Ge

Novel and general method for the preparation of peptidyl argininals

Abstract A general method for the synthesis of peptidyl argininals was developed which utilizes the novel building block N g -nitro-L-argininal ethyl aminal·HCl. The final aldehyde structure is generated by hydrolysis of the peptidic aminal moiety and can be applied to highly functionalized peptidic structures. The method is amenable to the preparation of large quantities of enantiomerically pure peptidyl argininals and was applied to the synthesis of two potent thrombin inhibitors.

A convenient large-scale chiral synthesis of protected 2-substituted 4-oxo-piperidine derivatives

Abstract A convenient large-scale chiral synthesis of protected 2-substituted-4-oxo-piperidine derivatives is described. Hetero Diels–Alder reaction between trifluoroacetic acid–boron trifluoride activated (1-phenyl-ethylimino)acetic acid ethyl ester and 2-trimethylsilyloxy-1,3-butadiene gave rise to a mixture of two diastereomers of 4-oxo-1-(1-phenyl-ethyl)-piperidine-2-carboxylic acid ethyl ester. Starting from (S)-1-phenyl-ethylamine pure adduct can be obtained by crystallization of the diastereomeric mixture. Reduction of the ester group gave rise to the corresponding hydroxymethyl analogue, which was subjected to further functional group transformations to yield the desired protected 2-aminomethyl-4-oxo-piperidine derivative without any racemization being observed.

A Facile Synthesis of Racemic 2-Aminomethyl-4-oxo-piperidine Intermediates

Abstract Facile access to the 2-substituted piperidine nucleus was achieved by a 3-component hetero Diels-Alder reaction. The use of an appropriately functionalized imine allowed the installation of a protecting group for both the piperidine and 2-position side chain nitrogens in one step. Also, by employing 2-trimethylsiloxy-1,3-butadiene, a reduction step was avoided, thus providing rapid entry into the piperidine core structure. This protocol led to the synthesis of some racemic 2-aminomethyl-4-oxo-piperidines; intermediates that were synthesized in multigram quantities.