Elsevier

Tetrahedron

Volume 74, Issue 44, 1 November 2018, Pages 6335-6365
Tetrahedron

Tetrahedron report 1175
Cascade reactions as efficient and universal tools for construction and modification of 6-, 5-, 4- and 3-membered sulfur heterocycles of biological relevance

Dedicated to Prof. Bogumil Brzezinski on the occasion of his 75th birthday.
https://doi.org/10.1016/j.tet.2018.09.022Get rights and content

Abstract

Sulfur-heterocycles are found in nature and they are recognized by biological systems as effective pharmacophores inducing anticancer, antimicrobial, antiviral, anti-diabetic activities via e.g. blocking functionality of many enzymes and receptors. Due to the biological importance of sulfur heterocycles, novel and efficient synthetic strategies, opening the access to regio- and stereoselective construction and functionalization of these scaffolds are in high demand. The advantages and some limitations of tandem strategies are discussed in view of challenges related to the construction of adequately functionalized or fused main heterocyclic sulfur frameworks of biological interest. In addition, examples of sulfur-heterocycles of important biological potency as well as domino reaction mechanisms revealing novel possibilities and ideas for construction of these attractive molecules, are reviewed. Bibliography presented in this review contains references to papers, which appeared mainly during the period from 2009 to 2018.

Introduction

Cascade reactions (also known as domino or tandem reactions) have been “invented” by the nature and applied in biosynthetic pathways of many groups of natural products as e.g. steroids, alkaloids, terpenes, polyether antibiotics or others [[1], [2], [3], [4], [5], [6], [7], [8]]. These transformations have become inspiration and powerful strategy for organic chemists working on economical and efficient syntheses of structurally diverse heterocyclic cores, important for e.g. pharmacy, agrochemistry and for designing of new materials [[9], [10], [11], [12], [13], [14], [15], [16], [17], [18]]. The first cascade reaction was performed by Robinson in 1917, who mixed succinaldehyde, methylamine and acetonedicarboxylic acid to afford an alkaloid - tropinone (1, Fig. 1) [19]. Formally, a cascade conversion should be at least composed of the two subsequent reactions (two virtual steps) without isolation of intermediates and addition of any reagents. The expressions “cascade/tandem/domino reaction” are used in literature also to describe the reactions of “one-pot” type, where some reactants are added to the reaction mixture at different times. In another meaning, the expressions “cascade/tandem/domino approach” were used in the context of convergent multistep total synthesis of selected target compounds, consisting of several cascade sequences. Cascade reactions, according to Nicolaou, can be divided into the following groups: nucleophilic cascades, electrophilic cascades, radical cascades, pericyclic cascades and transition-metal-catalyzed cascades etc., but very often these reactions are combined at different steps and the classification of tandem sequence to the particular group is then arbitrary [20]. Moreover, Tietze in his division of domino/cascade reactions distinguished additionally enzymatic cascade reactions [21]. The most advanced cascade approach, frequently very useful for total syntheses of many optically pure heterocycles of biological interest, is based on sophisticated enantio- or diastereoselective tandem reactions involving the use of different types of organocatalysts or metal catalysts [[22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34]]. Great advantage of cascade transformations is that, without time-consuming protection and deprotection of functional groups and isolation of intermediates, several bonds are broken and new ones are formed in a “one-pot” procedure in a relatively short time. Cascade approach may be even based on the above two reaction sequences [[35], [36], [37], [38]]. To classify multiple tandem conversions consisting of 2, 3, 4 etc. discrete reactions in a one set Stoltz et al., have proposed the following descriptors: duet, trio, quartet etc. instead of using not very precise terms as e.g. double, triple, quadruple cascade [27]. Taking all the above information into consideration, the cascade strategy fits perfectly into the broader area of chemistry called “green chemistry”, aimed toward preventing the environment pollution via e.g. elimination of hazardous materials in the form of by-products, elimination of wasting solvents and shortening the reaction time [39,40]. Up to now many reviews have been devoted to this dynamically developing area of chemistry, dividing cascade reactions according to e.g. their type and the type of catalysts used [[41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52]]. For example, various free radical cascades have been described earlier by McCarroll and Walton [53] and Wang [54]. Microwave assisted heterocyclization via tandem approach, as an interesting topic of the review, has been recently reported by Eycken et al. [55] Haibach and Seidel have described hydride-shift initiated cascades as a convenient route for C-H functionalization [56]. In turn, Zeng has divided sequential reactions, involving domino transformations, according to the type of newly formed bonds [57]. Although cascade reactions are irreplaceable in building of many natural products frameworks [58], a few reports have been devoted to organization of huge and fast-growing literature concerning domino reactions with a special emphasis on access to particular heterocyclic cores of biological interest [29,[59], [60], [61], [62], [63], [64]]. Therefore, in our work we attempted to collect recent advances in the application of different type cascade transformations (review covers mainly years 2009–2018) to gain some overview toward the most efficient and convenient synthetic methods giving access to construction and modification of the main biologically important sulfur heterocyclic cores.

Section snippets

Biological activity of the main sulfur heterocycles – short survey

Many enzymes able to form C-S bonds, and hence sulfur-containing heterocycles, as e.g secondary metabolites, are quite widespread in nature [65,66]. One of the best examples is β-D-glucoside from roots of Echinops grijissii containing benzothiophene moiety (2, Fig. 2), which is on the list of Chinese Pharmacopeia and has been used for treatment of many ailments [67]. Interestingly, it undergoes epimerization at C(6) stereogenic centre through the enol formation. Other active benzothiophenes

Thiophenes

Benzothiophene derivatives are a valuable group of heterocyclic derivatives for medicinal chemists, important for the synthesis of Raloxifene or Arzoxifene derivatives (3 and 4, Fig. 3). Recently, Zang et al. have reported cascade synthesis of 2,4-, 2,5-, 2,5,6- substituted benzothiophenes (type 21, Fig. 4) and analogous benzoselenophenes (type 22, Fig. 4) in metal-free conditions, obtaining good yields of respectively 30–75% and 30–60% [90]. Thanks to the use of available arylamines as stable

Conclusions and outlook

Taking into account the biological importance of sulfur-containing heterocycles as pharmaceuticals and agrochemicals we discussed in our review the recent literature regarding the tandem approach as a way to facile construction and desired functionalization of these scaffolds. Recently, due to the growing therapeutical and agricultural importance of chiral sulfur heterocycles, the regio-, diastereo- and enantioselective protocols giving access to their scaffolds have been intensively explored.

Acknowledgements

Authors are grateful for the financial support from Polish National Science Centre (NCN) – OPUS 10 project no. UMO-2015/19/B/ST5/00231.

Piotr Przybylski (M. Sc. 2000; Ph.D. - 2004 and habilitation - 2011) was born in Poznan, Poland in 1975. He is associate professor of organic chemistry, head of the research team specialized in chemistry and medicinal chemistry of natural antibiotics, their derivatives and other biologically relevant molecules at Faculty of Chemistry of Adam Mickiewicz University (AMU) in Poznan. He obtained „Maxima Cum Laude” award for the best graduates of the Faculty of Chemistry (2000) AMU Poznan, stipend

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    Piotr Przybylski (M. Sc. 2000; Ph.D. - 2004 and habilitation - 2011) was born in Poznan, Poland in 1975. He is associate professor of organic chemistry, head of the research team specialized in chemistry and medicinal chemistry of natural antibiotics, their derivatives and other biologically relevant molecules at Faculty of Chemistry of Adam Mickiewicz University (AMU) in Poznan. He obtained „Maxima Cum Laude” award for the best graduates of the Faculty of Chemistry (2000) AMU Poznan, stipend of President of Poznan city (2004), award for Ph. D. thesis of the Prime Minister of Poland (2005), stipend for Young Scientists (FNP, Warsaw 2005, 2006) and stipend for post-doc studies (FNP, 2007) in West Pomeranian University of Technology. His postdoctoral researches were realized in cooperation with Prof. F. Bartl at Humboldt University, Biophysikalische Chemie in Berlin (2017, DAAD stipend) and at Charité – Universitätsmedizin in Berlin. His research interests are focused on modification and determination of structure-activity relationships for natural products and their derivatives as well as are concerned with tautomerization, atropisomerization and proton transfer processes. His current studies are related to application of cascade approach to modification of 16-, 15- and 14-membered lactone macrolides and lactam ansamycin-type antibiotics. He has published 107 articles in journals of JCR database.

    Katarzyna Pyta-Klich was born in Poznan, Poland, in 1988. She received her Bachelor of Science (B.Sc. in Chemistry) as well as Master of Science degree (M.Sc. in Chemistry) from the Adam Mickiewicz University in Poznan in 2010 and 2012, respectively. During PhD studies she worked with macrolide antibiotic – Spiramycin to obtain new class of 16-membered unsaturated aglycones. She completed her PhD in chemistry under the supervision of Prof. Piotr Przybylski in June 2016 at Adam Mickiewicz University in Poznan. She is currently working as specialist in organic synthesis in Selvita company in Poznan. To this date she is a co-author of 8 articles.

    Krystian Pyta was born in Ostrow Wielkopolski, Poland, in 1984. He received his Master of Science degree (M.Sc. in Chemistry) from the Adam Mickiewicz University in Poznan in 2008. During his PhD studies worked with ansamacrolides to obtain new amine analogues of rifampicin. One of the most important achievement was an establishing that rifampin can exist in two forms non-ionic or ionic in dependence on the type of solvent. He completed his PhD in chemistry under the supervision of Prof. Piotr Przybylski in June 2012 at Adam Mickiewicz University in Poznan. In 2012 he received scholarship „Start” from Foundation for Polish Science and was a Scholar of Adam Mickiewicz University Foundation. He is also a laureate of Poznan City Scholarship. He is currently working with Professor Piotr Przybylski on modification of natural products to obtain new antibiotics or anticancer agents. Krystian Pyta is a co-author of 32 articles.

    Anna Janas was born in Gniezno, Poland, in 1992. She obtained her B.Sc. from Adam Mickiewicz University in Poznan in 2014 and received her M. Sc. degree at the same institution in 2016. Anna Janas is currently during her Ph.D. studies in Chemistry under the supervision of Prof. Piotr Przybylski at Faculty of Chemistry of Adam Mickiewicz University. To this date she is a co-author of 2 publications. Her research interests include the synthesis of new derivatives of 14- and 15-membered antibiotics with rebuilt saccharide arms, determination of their structures in solution and physicochemical properties influencing biological potency.

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