Efficient Synthesis of Nicotianamine and Non‐Natural Analogues

Abstract

An efficient synthesis of nicotianamine has been achieved by using a new strategy based on N‐alkylation. Sulfonamide activation proved to be necessary for the alkylation of the primary amine and the 2‐(trimethylsilyl)ethanesulfonyl group was easily introduced and found to provide the best compromise for the N‐alkylation and deprotection reactions. This new strategy enabled the preparation of several unnatural analogues including original molecules that will be useful as tools for plant physiology studies.

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

“…This key precursor for this strategy was prepared in three steps using L-tert-butyl aspartate (4) as a starting material (Scheme 1), like in a previously reported synthesis of azetidine. 10 Compound 4 was treated with benzyl chloroformate under usual conditions (NaHCO 3 , H 2 O/dioxane) to afford the Z derivative, which was readily reduced using the McGeary conditions 11 (preactivation of the acid with BOP then reduction with NaBH 4 ) to afford the desired alcohol 5 in 93% yield. Then, the alcohol 5 was converted into the iodide 6 using iodine, triphenylphosphine and imidazole.…”

Synthesis of Two Epimers of Pseudopaline

“…Recently, Zhang et al proposed a synthesis for 3 and 4 . Their strategy, similarly to the synthesis that we previously published for compound 5 , relies on the conversion of amines in sulfonamides, followed by N ‐alkylations for the construction of the main chain of the molecule. This approach implies drastic conditions for the final deprotection reaction (i.e.…”

Does the Exception Prove the Rule? A Comparative Study of Supramolecular Synthons in a Series of Lactam Esters

“…In detail we discuss here the synthesis and the X-ray structures of pyroglutamates 1 (iso-propylester) and 2 (tert-butylester), pyrohomoglutamic acid methyl ester (3) and its respective acid (4), the Nα disubstituted caprolactam [20][21][22][23][24][25] 5 and the three enantholactam 26,27 esters 6-8 ( Figure 2); additionally, we deliver full analytic a l characterization. Some of the title compounds are already known as useful building blocks and/or are part of biologically active compounds, such as pyroglutamic acid, 28,29 iso-propyl pyroglutamate (1), [30][31][32] tert-butyl pyroglutamate (2) [33][34][35][36][37] and pyrohomoglutamic acid (4) 38,39 and enantholactam 7. 40 The aim of this study was to learn how the ring size of the respective lactam and the nature of the carboxyl pendant affect the overall conformation and the hydrogen bonding pattern in the crystal packing.…”

“…In detail we discuss here the synthesis and the X-ray structures of pyroglutamates 1 ( iso -propylester) and 2 ( tert -butylester), pyrohomoglutamic acid methyl ester ( 3 ) and its respective acid ( 4 ), the N α -disubstituted caprolactam − 5 , and the three enantholactam , esters 6 – 8 (Figure ); additionally, we deliver full analytical characterization. Some of the title compounds are already known as useful building blocks and/or are part of biologically active compounds, such as pyroglutamic acid, , iso -propyl pyroglutamate ( 1 ), − tert -butyl pyroglutamate ( 2 ), − and pyrohomoglutamic acid ( 4 ) , and enantholactam ( 7 )…”