Synthesis and reactivity of compounds with cyclobutane ring(s). 10. Syntheses of squaric acid, its monoorthoesters, and related derivatives via [2 + 2] cycloadditions of tetraalkoxyethylenes with heterosubstituted ketenes

Belluš, D.

doi:10.1021/jo01322a004

Cited by 39 publications

(7 citation statements)

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“…Based on the calculated charges shown in Table 2, the exocyclic carbon atom, C 2 , carries a significant negative charge for all species 1-6. The negative charge on C 2 in species 1-6 is largest when two N-CH 3 groups are present (6), and the negative charge is smallest when two sulfur atoms (3) are present in the ring. The calculated charges, predict that 6, with two -N-CH 3 groups, will be the most nucleophilic species in the series.…”

Section: Resultsmentioning

confidence: 99%

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Theoretical studies of five-membered ring ketene acetals

et al. 2009

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Cyclic ketene acetals are a class of organic molecules characterized by a nucleophilic exo-methylene carbon attached to a carbon with two adjacent O, N, or S atoms. We have carried out a systematic computational study of a series of five-membered cyclic acetals like 2-methylene-1,3-dioxolane and its OS, SS, NO, NS, and NN analogs as well as all the protonated species. The calculations were performed at the MP2 level using a triple zeta plus polarization basis set. The nucleophilicity was discussed in terms of geometrical factors, calculated atomic charges, calculated chemical shifts, and proton affinities. All the six neutral species were strong nucleophiles. The NN analog was predicted to be the strongest and the SS analog the weakest nucleophile.

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Section: Resultsmentioning

confidence: 99%

“…Cyclic ketene-O,O-acetals, such as 2-methylene-1,3-dioxolane, 1, and its -O,S-, -S,S-, -O,N-, -N,S-, and -N,N-analogs, 2-6, respectively, are a class of organic nucleophiles that have attracted substantial interest [1][2][3][4][5][6][7]. Each of these compounds has a nucleophilic exo-methylene carbon.…”

Section: Introductionmentioning

confidence: 99%

Theoretical studies of five-membered ring ketene acetals

et al. 2009

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“…[100]. Interestingly, the carbon-14 radiosynthesis of squaric acid reported by Heys and Chew [101] was modelled on the synthetic route reported by Bellus [102].…”

Section: Squaric Acid Familymentioning

confidence: 97%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

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Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids, peptide bonds and phosphonates. Moreover, the squaryl metaphor is a precursor to complex organic molecules involving functional group interchange (FGI) and rearrangements. This article discusses the application of these metaphors in the area of neurochemistry, especially NMDA receptors. An important area of drug design is the inhibition of angiotensin II enzyme by the use of losartan. This commercial drug contains a tetrazole moiety that can be modified using the squaryl group to give a semisquarate derivative. These concepts can extend to the semisquarate of ibuprofen. Moreover, a discussion on peptidomimetics regarding the substitution of the peptide bond for squaramide allows for a change in the biological properties due to modification at the peptide bond. Furthermore, the topic on how squaryl metaphors can be exploited primarily by the central 1,3-hydroxyamide sequence to the generation of a novel class of HIV protease inhibitors. Also, squaryl metaphors can be used to develop potential inhibitors of glutathione and novel anti-migraine drugs. The discussion continues on the design of anticancer drugs: in particular, a novel class of metalloproteases, including phosphonates for semisquaramides, leading to squaryl nucleosides. This review concludes with the application of squaryl metaphors in the design of positron emission tomography (PET) and magnetic resonance imaging (MRI) agents towards theranostics. describe the ability of individual functional chemical groups to mimic other moieties [2,3]. KeywordsErlenmeyer rationalised these concepts and categorised isosteres into atoms, ions and molecules based on the valence level of electrons [4]. A further understanding by Friedman led to the term bioisosterism to include all atoms and molecules that fit the broadest definition of isosteres [5]. This approach was independent of whether the drug was an agonist or an antagonist towards biological activity.Moreover, Thornber applied the term bioisosterism to include subunits, groups or molecules that possess physicochemical properties of similar biological effects [6]. Finally, in 1991 Burger widened the definition of bioisosteres to include compounds or groups that possess similar molecular shapes and volumes independent of agonists or antagonists [7]. REVIEW ARTICLE Squaryl KitsonThese bioisosteres would require approximately the same distribution of electrons and give a high probability of generating comparable physical properties such as hydrophobicity [8]. Currently, bioisosterism is one of the most useful tools to the medicinal chemist in rational drug design and in particular regarding the carboxylic acid bioisosteres [9]. The carboxylic acid functional ...

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“…His work at the Slovak Academy of Sciences (1961–1967) and later as postdoctoral fellow with O. Jeger and K. Schaffner at the ETH Zürich (1967–1969) pioneered the field of organic photochemistry 1. During his many years at Ciba–Geigy’s Central Research Laboratories (CRL) in Basel (1969–1985), he made many outstanding and innovative contributions to the field of bioactive small‐ring compounds,2 including the synthesis of analogues of the natural insecticide pyrethrum,3 of the mycotoxin moniliformin,4 and of squaric acid 5. In 1978 he discovered a new, broadly applicable reaction that allows ring enlargement by four carbons in one step,6 a reaction which is now known as the Belluš–Claisen rearrangement.…”

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confidence: 99%