Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• Two kinds of [3 + 2] cycloaddition intermediates generated from the three-component reactions of 2-bromobenzaldehydes and maleimides with amino esters or amino acids were used for a one-pot N-allylation and intramolecular Heck reactions to form pyrrolidinedione-fused hexahydropyrrolo[2,1-a

• synthesis of hexahydropyrrolo[2,1-a]isoquinolines by employing stable 1,3-dilpolar compounds generated from amino esters [15][40] or isoquinolines [41][42][43][44][45][46][47][48][49]. We like to report in this paper our effort on the synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines

• synthesis of analogs of 9 (Scheme 4). A variety of [3 + 2] cycloaddition adducts 5 bearing different R, R1, R2 and R3 groups, derived from amino esters 1, 2-bromobenzaldehydes 3 and maleimides 4, were subjected to N-allylation followed by intramolecular Heck reaction to pyrrolidinedione-fused

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• -decyl-2,3-pyrrolidinedione ring linked to the ureido dipeptide L-Phe-L-Val. The 2,3-pyrrolidinedione ring is a quite unusual skeleton. A limited number of compounds containing this system have been synthesized so far [5][6][7] and, to the best of our knowledge, natural compounds with a 2,3

• -pyrrolidinedione nucleus are quite rare [8][9][10][11]. The lack of similar compounds may be due to the instability of the 2,3 pyrrolidinedione moiety [12]. Indeed, while developing the total synthesis of leopolic acid A, we encountered several difficulties in the construction of the ring, most of the

• intermediates being unstable [4]. In light of these results, we intended to investigate the role of the 2,3 pyrrolidinedione ring by replacing it with a more stable isomeric 2,4-pyrrolidinedione moiety. Actually, 2,4 pyrrolidinediones (tetramic acids) have recently attracted considerable attention for their

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• formaldehyde through [5 + 1] annulation to afford a novel polycyclic scaffold bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide in stereoselective fashion. Keywords: [5 + 1] annulation; [3 + 2] cycloaddition; one-pot reactions; stereoselective synthesis

• [12][13][14][15][16][17], our lab has introduced a series of synthetic methods for heterocyclic compounds I–VI bearing heterocyclic rings such as hydantoin, pyrrolidine, pyrrolidinedione, piperazinedione, and dihydrobenzodiazepinedione (Scheme 1) [4][18][19][20][21]. All these scaffolds were prepared

• new sequence initiated with a three-component [3 + 2] cycloaddition for preparing polycyclic scaffold 1 bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide rings. Those heterocyclic fragments could be found in bioactive compounds such as bromodomain, thrombin

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• Veterinary Medicine - Microbiology and Immunology, Università degli Studi di Milano, via Celoria 10, I-20133 Milano, Italy 10.3762/bjoc.12.159 Abstract The first total synthesis of leopolic acid A, a fungal metabolite with a rare 2,3-pyrrolidinedione nucleus linked to an ureido dipeptide, was designed and

• carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds

• suggests that they could be considered as promising candidates for future developments. Keywords: antimicrobial; heterocyclic compounds; natural products; pyrrolidinedione; total synthesis; Introduction Great concern has recently been expressed about the diminishing efficacy of current antibiotic

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• the amino group to the carbonyl group produces the polyfunctionalized 2-pyrrolidinone 1. There is one reactive enamine unit in the obtained 2-pyrrolidinone 1. Under the catalysis of p-toluenesulfonic acid, the enamine moiety in 2-pyrrolidinone 1 was easily hydrolyzed to yield a 2, 3-pyrrolidinedione

• (D) and piperidine. Then 2,3-pyrrolidinedione D transforms to the more stable enol-form through the keto–enol tautomerism. Because the enol connects to both ester and amide groups, it has much stronger acidity and is deprotonated by piperidine in the solution to give the piperidinium 2-pyrrolidinon-3

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• were absent from the 1H NMR spectra of the crude product mixture. For adduct 18, only one diastereomer was obtained (38% yield after workup), which, according to the observed NOE effects, has the pyrrolidinedione ring and the (CH2)2SCH3 chain in exo positions. This means that the cycloaddition has gone