Direct Access to L‐Azetidine‐2‐carboxylic Acid

Abstract

A straightforward synthesis of L‐azetidine‐2‐carboxylic acid is described, leading to both orthogonally protected versions or totally deprotected L‐Aze. The starting material is a commercially available aspartic acid derivative, whose chirality is conserved. The (2‐trimethylsilyl)ethanesulfonyl protecting group (SES) acts as a leaving group on the hydroxy function and serves as an activator for the amine function, which is the key‐step of the reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The crystallographic structure of thermoNicotianamine synthase with a synthetic reaction intermediate highlights the sequential processing mechanism

“…The synthetic approach was based on the assembly of two building blocks by N-alkylation: 9 an activated amine derived from glutamic acid in one part and an iodine synthon, a mimic of the aminopropyl moiety of SAM, on the other part.…”

Efficient Synthesis of Nicotianamine and Non‐Natural Analogues

“…Then the alcohol 3 was converted into the iodide 4 by using iodine, triphenylphosphane and imidazole. [11] In the first alkylation step, tert-butyl l-azetidine-2-carboxylate [12] (5) was successfully N-alkylated with the iodide derivative 4. The optimized alkylation conditions, DIEA (2 equiv.)…”

“…We then extended this strategy to produce three synthetic analogues (Figure 2) by replacing the carboxy-azetidine ring with proline (10), silaproline (11) [18] and pyroglutamic acid (12), thus modifying the physicochemical properties of the molecules. These compounds were used as probes in plant experiments.…”

DISCUSSION ADDENDUM for: 2‐Trimethylsilylethanesulfonyl Chloride (SES‐Cl)

“…In addition to its use in introducing a protecting group, SES-Cl can also effectively acidify an amine nitrogen and simultaneously provide a leaving group, as demonstrated in a synthesis of L-azetidine-2-carboxylic acid (9), a naturally occurring non-proteogenic amino acid. 9 N-Sulfonylation of amino alcohol 4 with SES-Cl, followed by treatment of the resulting bis-SES compound 5 with base, gave the orthogonally-protected cyclic amino acid 6 (Scheme 2).…”