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.

We present an optimized procedure for the synthesis of (S)-vinylglycine from (S)-methionine. The key step is a solvent free pyrolysis of an intermediate sulfoxide at high temperature. Using our optimized reaction conditions, Cbz-protected vinylglycine was obtained in high yield and with almost no side products. The protocol is scalable, fast and avoids the use of poisonous reagents.

Dialkyl phosphinates are valuable peptide mimics for metallopeptidase targets. Despite their large pharmaceutical potential, the synthesis of many phosphinates remains challenging. An additional drawback for many applications is the high polarity of the phosphinate group. Herein we describe the synthesis of stereoisomerically pure GPI (1), a phosphinate with high binding affinity for the cancer specific zinc peptidase PSMA (prostate specific membrane antigen). In addition, analogous cyclic phosphinate esters 13, 16 and 23 are reported that might be useful as less polar ligands for metallo peptidase binding. The key step to these new 1,2-oxaphosphorinan-2-ones is an intramolecular cyclization of an intermediate H-phosphinate. The cyclizations work with modest diastereoselectivities of ~2:1 in favor of the trans arrangement of substituents at 2-and 4-position of the 1,2-oxaphosphorinan-2-one scaffolds.

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