Synthesis and NMR spectroscopic studies of optically active derivatives of γ‐aminobutenoic acids and 2‐amino‐pyrrolin‐4‐ones

Abstract

An efficient method for the preparation of optically active derivatives of γ-amino-butenoic acids and their cyclic derivatives, 2-amino-pyrrolin-4-ones, from α-amino acids is described. Partial racemization accompanies the formation of initial unsaturated γ-amino-β-hydroxy esters 5-8, as determined by chiral HPLC.

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

“…Accordingly, our route began with the addition [ 31 – 33 ] of 2-lithiopropionitrile to methyl N- Boc-prolinate ( 15 ) to give α-cyanoketone 16 which was used in crude form or purified by chromatography to a colorless solid, albeit with significant loss in yield. The removal of the Boc protecting group under acidic conditions was accompanied by cyclization in situ [ 14 – 15 34 – 35 ] and pyrrolizinone derivative 17 was obtained efficiently on a multigram scale over two steps.…”

A Novel Access to 2-Aminofuranones via Cyclization of Functionalized γ-Hydroxy-α,β-butenoates Derived fromN-Hydroxybenzotriazole Esters of α-Hydroxy Acids

“…3 Sotolone (3-hydroxy-4,5-dimethyl-2-furanone), a powerful flavour compound found in several foods and spices, was synthesized from 3-amino-4,5-dimethyl-2-furanone. 4 Our experience in the synthesis of 2-aminopyrrolinone derivatives (Figure 1, II) 5,6 prompted us to investigate the construction of the novel class of 2-amino furanones (Figure 1, III) with potential biological activity.…”

Solid Phase Synthesis of Substituted 2-Amino-4-Pyrrolinones via Spontaneous Postcleavage Cyclization

“…The derived 4-amino-2butenoates were cyclized to optically active 2-substituted-4-pyrrolinones either in acidic medium or upon standing in CDCl 3 . 10,11 During the course of our research programme involving the use of activated esters of N-substituted-L-a-amino acids in the C-acylation reactions of active methylene compounds, we have demonstrated the powerful acylating properties of benzotriazolyl esters and used them as starting material for the synthesis of optically active tetramic acids and 4-amino-functionalized 2-butenoates. 12,13 These results encouraged us to explore the transfer of our well-established solution phase methodology to the solid phase.…”

“…17 The NMR spectroscopic data as well as the physical data are in full accordance with those previously reported for these compounds. 10,18 The enantiomeric excess (ee) of the 2-amino-4-pyrrolinones 8-11 was as determined by HPLC analysis using a chiral stationary phase (Table 1). 19 It is postulated that, in the acidic medium, the release of the nitrogen atom from the resin is followed by nucleophilic attack to the carbon of the protonated CN group, leading to the formation of the stable five-membered amino-pyrrolinone ring.…”