Synthesis of 3-alkyl-2-benzamido-4-hydroxy-2-butenoic acid .gamma.-lactones from alkyl cuprates. Attempted transformation to 2,3-diaminocarboxylic acids by hydrogenation and Curtius rearrangement

Abstract

The reaction of lithium dialkylcuprate reagents with 2-benzamido-3-bromo-4-hydroxybut-2-enoic acid 7-lactone (8) gave the corresponding 3-alkylbut-2-enoic acid 7-lactone derivatives 3. With lithium dimethylcuprate, a low yield of product was obtained; however, use of a new combined cuprate reagent, (CHg^CuLi-CK^Li-BF^, provided 3-methylbut-2-enoic acid 7-lactone (10) in good yield. Reaction with lithium di-n-butylcuprate, and subsequent oxidative quenching with nitrobenzene, furnished in good yield the 3-n-butyl derivative 11. The cuprate prepared from the acetonide of (S)-4-chlorobutane-l,2-diol, when coupled by the same procedure, gave the chiral lactone 15; product 15 is of interest as a synthetic precursor to streptolutine, the amino acid component of the dioxopiperazine antibiotic 593A. Two key steps, reduction and Curtius rearrangement, were studied for the conversion of 2-(acylamino)but-2-enoic acid 7-lactones to 2,3-diamino carboxylic acids. The unsaturated lactone 10 underwent reduction with palladium on carbon at 80 °C and 300 psi of hydrogen; under these conditions the benzamido aromatic ring also was reduced. The Curtius rearrangement was studied for conversion of the aspartic acid monoamide 18 and related compounds to the corresponding 2,3-diamino carboxylic acids. The effect of selected amino and carboxyl protecting groups on the course of the rearrangement reaction was determined.

Synthesis of a Nitrogen Analogue of Sphingomyelin as a Sphingomyelinase Inhibitor

“…In this reaction, the intermediary isocyanate was successfully trapped with the vicinal amide nitrogen to afford the corresponding cyclic imidazolidinone. In the literature, few examples can be found that use this intramolecular imidazolidinone formation method in natural product synthesis ).…”

Stereoselective Bromination−Suzuki Cross-Coupling of Dehydroamino Acids To Form Novel Reverse-Turn Peptidomimetics: Substituted Unsaturated and Saturated Indolizidinone Amino Acids

“…The stereoselective β-bromination of dehydroamino acid esters has been well documented . Nunami and co-workers described that the Z -selectivity of the bromination was improved by increasing the bulkiness of β-substituents …”