Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• this compound class is derived from the aromatic precursor 3,5-dimethylorsellinic acid (DMOA). In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• -phenacylideneoxindoles resulted in the two different novel dispirooxindole skeletons. Conclusion In summary, we have investigated the base-promoted multicomponent reaction of 3-methyleneoxindoles, dimedone, isatins and ammonium acetate. The reaction showed very interesting molecular diversity and diastereoselectivity

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• acetylenedicarboxylates and 5,6-unsubstituted 1,4-dihydropyridines. The advantages of the reaction include the use of readily available starting materials, simple reaction conditions, without using any catalyst, high molecular diversity and atomic economy. Therefore, this reaction not only successfully developed

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• , isocyanide multicomponent reactions are the way to prepare the necessary drugs "of tomorrow", and the possibility to combine such reactions gives a powerful method to rapidly and qualitatively expand the molecular diversity of biologically active compounds. The following possible combinations of IMCR have

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• ][4][5], because it contains one carbonyl group, two cyano groups, and an activated methylene unit. Phenacylmalononitrile exhibits versatile reactivity, high synthetic efficiency and molecular diversity and has been widely employed in many synthetic reactions [6][7][8][9][10]. On the other hand

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• advantages of using readily available substrates, simple operation, good yields, and molecular diversity, which enable it to find potential applications in heterocyclic and medicinal chemistry. Experimental 1. General procedure for the preparation of the spiro[cyclohexane-1,3'-indolines] 3a–w: In an

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• capacity and modes to achieve the uphill task easily [19]. The contemporary organic chemistry procedure involving microwave heating has paved way for the molecular diversity that helps in reducing the time required for the drug discovery process. As multicomponent reactions and microwave reactions hold

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• containing an isoxazole moiety is of key interest in this study since previously our group reported [19] a successful usage of 3-aminoizoxazoles as unusual amine components in the Ugi-4CR reaction and here we continue to build molecular diversity of isoxazole-derived Ugi products and their successors

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• and (ii) permits to synthesize pyrroles with a high potential of molecular diversity and complexity. However, to date, the productivity for creating molecular diversity and complexity has yet to be fully displayed. In addition, some of the reported approaches were established on the basis of using

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• ]pyrimidines via a cascade of elementary stages that is unusual for such transformations. Thus, we extended the molecular diversity of the compounds obtained by introducing an additional azolyl substituent to the pyrimidine ring. Alternative structures A and B for the tetrahydroazolopyrimidines 4. Molecular

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• synthetic biology to engineer pathways that will expand molecular diversity, especially around scaffolds associated with high-value compounds. The biosynthetic logic of terpene formation differs significantly from the logic employed by other classes of secondary metabolite biosynthetic pathways. Bacterial

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• rhodium catalyst to promote C(sp2)–H activation in the presence of a suitable directing group. The Ugi-azide reaction provides broad molecular diversity and enables the introduction of the tetrazole moiety, which may further assist the catalytic reaction by coordinating the metal center. The scope of the

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• derivatives containing pyrrole and 2-aminoimidazole fragments in their structure were found among the metabolites of these marine organisms [1]. This group of compounds is characterized by an exceptional molecular diversity. The main structural types of these substances are shown in Figure 1. The metabolites

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• conformational constraints. Wessjohann and co-workers also demonstrated MiBs based on the Passerini-3CR [49]. The strategy is similar to Ugi-MiBs in which it provides molecular diversity in a few steps due to variable combinations of bifunctional building blocks that can be easily changed to provide skeletal

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• -stage modification of complex products such as steroids. On the other hand, both the alkyne and the iodoarene moiety can be modified through post-transformation reactions thereby increasing the molecular diversity accessible with this process. The mechanism of the reaction (Scheme 11b) would first

• previous strategy, not only this process enables to increase the molecular diversity, but it also displays a higher atom-efficiency as only 1.1 equivalents of the λ3-iodane are required to achieve good to excellent conversions. In addition, it should be pointed out that the tandem reactions based on the

• inspiration for the conception of new multicatalytic cascades that receive increasing attention in organic synthesis [111][112]. Extending their scope in terms of molecular diversity and complexity is expected from their application starting from other classes of λ3- or λ5-iodanes. Strategies to address the

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles. Keywords: convertible isocyanides; lactams; molecular diversity; oxindoles; transamidation; Introduction The Ugi-multicomponent coupling reaction [1][2], followed by post-modification

• economical, simple and generate ample molecular diversity with the ease of using readily available starting materials. Developing new, post-modified Ugi-four-component reaction (Ugi-4CR) transformations in domino cyclization [12][13][14][15] sequences are very important for achieving unprecedented chemical

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• 1,5-disubstituted tetrazoles due to the intrinsic generation of molecular diversity [11][12][13][14][15]. As the Ugi reaction also requires an amine component, we envisaged that reactions of hydrazino compounds (RNHNH2) with TMSN3 could furnish useful compounds bearing both the hydrazino and the

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• coupling reactions as well as nucleophilic substitutions have been performed successfully in order to increase the molecular diversity. Keywords: aerobic oxidative coupling; imidazo[1,2-a]-N-heterocycles; gem-difluoroalkyl derivatives; propargylic fluorides; Introduction Nitrogen-containing heterocyclic

• as an attractive precursor to increase the molecular diversity around this scaffold. In order to explore this possibility, we performed two Suzuki–Miyaura reactions, as representative examples of Pd-catalyzed coupling processes (Table 3). They gave the target molecules 8 and 9 in 46% and 53% yields

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• reactions, a large number of structurally diverse compounds could be synthesized. In addition, a one-pot Biginelli–Passerini tandem reaction was demonstrated. All products were carefully characterized via 1D and 2D NMR as well as IR and HRMS. Keywords: Biginelli reaction; molecular diversity

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• ; nitrogen heterocycles; rearrangement; Introduction One of the foci of current organic synthesis is the exploration of new chemical space, with an emphasis on significant heterocyclic molecular diversity [1][2]. Direct applications of such advances in medicinal chemistry, chemical biology and nanochemistry

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• with 40% yield. To further improve the yield and add to the molecular diversity, N6-benzoyladenine 17 was used as a base to give nucleoside 14 in 87% yield (Scheme 2). All benzoyl protecting groups were removed simultaneously by using ammonia saturated methanol in a sealed press tube to give 15 in 96

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• reduction of both the yield and the reaction rate. The application of sonication to shorten the reaction times was also useful, since compound 4 was obtained after 6 hours with the same dr, although in a lower yield (Table 1, entry 14). To exploit the potential of the Ugi reaction to introduce molecular

• diversity by a one-pot operation, we attempted to realize a four-component (4CR) version. An equimolar mixture of isatin and (S)-phenyl ethylamine was reacted with 2a (2 equiv) and 3a (2 equiv) in methanol in the presence of MgSO4 as a dehydrating agent to promote the formation of the ketimine

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• of the corresponding β-formylketone/ester substrates or the intolerance of β-formylketones/esters in the Biginelli reaction. In regard to the daily increasing requirements on molecular diversity, developing powerful methods for the rapid synthesis of DHPMs with diverse and unprecedented substitution

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• Lorenzo Giardini and Sara Piano for preliminary exploratory experiments, Andrea Armirotti and Martina Spallarossa for HRMS, PRIN 2009 ("Synthetic Methodologies for Generation of Biologically Relevant Molecular Diversity") and the University of Genova for funding.

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• ], arylidenerhodanines [25][26], α,β-unsaturated lactones [27], nitrostyrenes [28], acrylic and propiolic esters [29], acrylonitriles [30] and arylidene-1,3-dimethylpyrimidine-2,4,6-triones [31] have been reported. However, the molecular diversity of suitable building blocks for construction of spirooxindoles is by far