Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• . Keywords: green protocol; mild conditions; no additional catalyst; solvent free; triple role of melt; Introduction In recent years, dihydropyrimidinones (DHPMs) and their derivatives have attracted considerable attention due to the multifaceted pharmacological properties of this class of compounds [1][2

• inhibits the motor activity of mitotic kinesin Eg5 and is therefore considered as a lead for the development of anticancer drugs [16]. Of particular interest are 5-unsubstituted DHPMs [17], such as compounds 1 and 2, which possess neuronal sodium channel blockade activities (Figure 1). Other examples are

• ester group at C5 and an alkyl group at C6 position. A group of researchers from Merck reported the synthesis of 5-unsubstituted DHPMs via a Biginelli reaction followed by saponification of the ester and subsequent decarboxylation [22]. Later, Bussolari and McDonnell demonstrated the synthesis of 5

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• Biginelli reaction is a renowned and tunable MCR to synthesize the pharmacologically active 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs, Biginelli products) [31]. These compounds occupy an important position in the fields of natural products and synthetic organic chemistry owing to their potential

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• -tetraphenylbutanetetraol; chiral phosphoric acid; Introduction Dihydropyrimidinethiones (DHPMs) are an important class of heterocyclic compounds featuring in a large number of natural and artificial compounds possessing various biological activities, and serving as key intermediates for the synthesis of medical drugs [1

• ][2][3][4]. In the last decade, chiral DHPMs showed valuable pharmacological properties such as antiviral, antitumor, antibacterial, anti-inflammatory, and antihypertensive effects [5][6]. However, the individual enantiomers of DHPMs were found to exhibit different or even opposite pharmaceutical

• DHPMs becomes an urgent and paramount task. In connection with this, multicomponent Biginelli and Biginelli-like reactions of aldehydes, urea/thiourea, and enolizable carbonyls revealed as very efficient tools to prepare DHPMs [3]. Although the Biginelli reaction was firstly discovered over a century

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• oxidant (Scheme 22) [67]. Heterocycles in drugs are not only restricted to five-membered rings. Pyridines, pyrazines, pyrimidines, pyridazines are all common functional groups in biologically active compounds. Liu et al. have published the visible light-catalysed oxidation of dihydropyrimidines (DHPMs

• were employed. Though the scope of the reaction is quite broad, variation is only investigated in the C4 and C5 positions of the DHPMs. Variability at C1 and C6 are not investigated. The variation of the ester and the C4 ligands, however, is good, with some interesting products being presented. The

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

• aldehydes, electron deficient alkynes and ureas/thioureas have been smoothly performed to yield a class of unprecedented 3,4-dihydropyrimidinones and thiones (DHPMs). The reactions are initiated by the key transformation of an enamine-type activation involving the addition of a secondary amine to an alkyne

• , which enables the subsequent incorporation of aldehydes and ureas/thioureas. This protocol tolerates a broad range of aryl- or alkylaldehydes, N-substituted and unsubstituted ureas/thioureas and alkynes to yield the corresponding DHPMs with specific regioselectivity. Keywords: alkynes; DHPMs; diversity

• ; enamine activation; multicomponent reactions; Introduction DHPMs are well-known heterocyclic scaffolds with abundant biological relevance [1][2][3]. The DHPM backbone has been found in a class of marine natural products possessing anti-HIV activity [4]. What’s more, diversified other biological

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• chiral spirocyclic SPINOL-phosphoric acids. Keywords: Biginelli-type reaction; chiral phosphoric acid; dihydropyrimidinone; iodine; multicomponent reaction; Introduction The dihydropyrimidinones (DHPMs) have exhibited interesting and multifaceted biological activities, such as antiviral, antitumor

• Biginelli [3][4]. Among them, the Biginelli multicomponent reaction, involving a multicomponent condensation of aldehyde, β-ketoester, and urea, provides an easy access to the preparation of DHPMs, because multicomponent reactions (MCRs) are considered with high facileness, efficiency and economy in organic

• chemistry [5][6][7][8]. Recently, many one-pot variants of Biginelli-type reactions for the preparation of novel DHPMs using various active methylene compounds [9][10][11][12][13][14][15], such as enaminone, cyclic β-diketones, acetophenone, benzocyclic ketones and β-oxodithioesters etc., have also been

Zeolite catalyzed solvent- free one-pot synthesis of dihydropyrimidin- 2(1H)-ones – A practical synthesis of monastrol

• Mukund G. Kulkarni,
• Sanjay W. Chavhan,
• Mahadev P. Shinde,
• Dnyaneshwar D. Gaikwad,
• Ajit S. Borhade,
• Attrimuni P. Dhondge,
• Yunnus B. Shaikh,
• Vijay B. Ningdale,
• Mayur P. Desai and
• Deekshaputra R. Birhade

Beilstein J. Org. Chem. 2009, 5, No. 4, doi:10.3762/bjoc.5.4

• monastrol, a potent inhibitor of kinesin Eg5. Keywords: Biginelli reaction; DHPMs; neat; MCR; zeolite; Introduction The Biginelli reaction is a well-known multicomponent reaction involving a one-pot cyclocondensation of an aldehyde, β-ketoester and urea/thiourea [1][2][3]. Multicomponent reactions (MCRs

• ) have recently gained tremendous importance in organic and medicinal chemistry. The main contributing factors are the high atom economy, wide application in combinatorial chemistry and diversity-oriented synthesis [4][5][6][7][8][9][10]. In general, the dihydropyrimidones (DHPMs) are known for their

• diverse important biological activities like antiviral, antitumor, antibacterial and antiinflammatory properties [11][12][13]. The first report of the Biginelli reaction dates back to 1893. This involved a very simple and straightforward procedure for the synthesis of DHPMs. A one-pot cyclocondensation of