Synthesis of Cyclic Hydrazino α-Carboxylic Acids

Abstract

We present a review of different methods for the preparation of five-and six-membered cyclic hydrazino a-carboxylic acids and their derivatives. These heterocycles are common building blocks in pharmaceuticals and many natural products. In addition, hydrazino carboxylic acids have been used as auxiliaries and intermediates in organic syntheses and selected applications are highlighted in this summary. For six-membered heterocycles (piperazic acids), the literature since 1998 is covered as a follow-up to the review by Ciufolini and Xi.

Catalytic N-radical cascade reaction of hydrazones by oxidative deprotonation electron transfer and TEMPO mediation

“…It should be noted that the groups of Han 29 30 and Chiba 31 have also independently reported stoichiometric amounts of tetramethylpiperidine-1-oxyl (TEMPO)-mediated intramolecular cyclization of hydrazonyl radicals for pyrazoline synthesis. Inspired by these studies, we considered exploration of the reactivity of hydrazones in catalytic N-radical cascade reactions to assemble biologically and synthetically important dihydropyradazine scaffolds 32 , inaccessible using other thermal methods 29 30 31 33 or our own previous protocols.…”

Synthesis of Dihydropyrazoles via Ligand-Free Pd-Catalyzed Alkene Aminoarylation of Unsaturated Hydrazones with Diaryliodonium Salts

“…The synthesis of privileged N–N bond-containing dihydropyrazoles has gained a great deal of research effort from the synthetic community due to their prevalence in many natural products and pharmacologically active molecules as well as versatile utility as building blocks in organic synthesis (Figure ). Many recent methods for their preparation have mainly focused on catalytic cyclization or cycloaddition reactions using organocatalysts or metal catalysts . Given the important effects of the substitution patterns and structural diversity on their biological profile, development of general, efficient and operationally simple methods for the construction of such a class of nitrogen heterocycles is still highly desirable.…”

Stereoselective synthesis of (R)- and (S)-1,2-diazetidine-3-carboxylic acid derivatives for peptidomimetics

“…Cyclic α-hydrazino acids and their derivatives have been shown to possess a diverse set of biological activities. 1 They have been isolated from numerous natural sources, including plants, marine organisms and bacteria. Examples include the potent cytotoxins piperazimycin A–C from Streptomyces sp.…”