Synthesis of 1, 5‐ Disubstituted Tetrazole via Ugi Azide Reaction: An Asymmetric Induction Approach

Abstract

The Ugi‐azide reaction of an enantiopure amino acid derived isocyanides, amino acid esters, aldehydes and TMS‐N3 in MeOH:THF solvent system at 50 °C yielded peptidomimetics comprising tetrazole as amide bond isostere. Both N‐terminal (α‐isocyanoesters) and C‐terminal isocyanides (Nβ‐Cbz‐protected amino alkyl isocyanides) have been employed to yield diversified tetrazole peptidomimetics, having the possibility of further derivatization through either N‐ or C‐terminal chain elongation. Ugi‐azide reaction is a isocyanide based multi‐component reaction (IMCR), as a result, change in amino acid derived isocyanides had given structurally diverse products of biological interest. Good yields of products were obtained after column purification and were stable for shelf storage. The products are novel and were well characterized by Mass, 1H NMR and 13C NMR spectral studies. The present method offers several advantages such as one‐pot simple procedure, high yields and easy purification of products.

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

“…Our previous work shows that Charette's methodology is also not applicable in this case, as it does not lead to the formation of an imine [23]. Luckily, we were able to use a formerly established strategy based on Georg's procedure with standard Ugi-azide reaction conditions [35][36][37][38][39] in a one-pot, tandem process. Subjecting glucose-derived lactam 1 to such a procedure gave the desired product in good yield, but with virtually no diastereoselectivity, as shown in Scheme 2.…”

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

“…Our previous work shows that Charette’s methodology is also not applicable in this case, as it does not lead to the formation of an imine [ 23 ]. Luckily, we were able to use a formerly established strategy based on Georg’s procedure with standard Ugi–azide reaction conditions [ 35 – 39 ] in a one-pot, tandem process. Subjecting glucose-derived lactam 1 to such a procedure gave the desired product in good yield, but with virtually no diastereoselectivity, as shown in Scheme 2 .…”

Synthesis of Nβ-Protected Amino Sulfenyl Methyl Formamides and Sulfonyl Methyl Formamides: A Simple Protocol

“…It is important to note that amino acid- and peptide-derived formamides and its isocyanides have gained attention in MCRs for medicinal chemistry and drug discovery applications . We also explored the C-terminal modification of amino acids to prepare formamides and isocyanides (Figure ) and employed in MCRs for the construction of a new class of peptidomimetics . With a view toward enabling a new class of formamides as well as isocyanides, we considered that sulfonyl formamides derived from chiral amino acids (Figure b) might be useful for generating a novel class of peptidomimetics.…”