http://www.mdpi.com/journal/molecules/special_issues/spiro_compounds/ Spirocompounds can be defined as cyclic molecules containing at least two rings joined together by a single carbon atom. This unique structural feature has been observed in natural products and has also been the target of methodological studies and syntheses. This special issue of Molecules is aimed at all aspects of spirocompounds. Submissions dealing with new methods of spiroannulation, the use of spirocompounds as intermediates in synthesis, and the isolation/characterization of new natural products are particularly welcomed. Any submission dealing with other aspects of spirocompounds will also be considered. Manuscript submission Manuscripts should be prepared according to the Instructions for Authors and submitted by e-mail to molecules@mdpi.org, with copy to the Guest Editor Dr. Guy Plourde, E-mail: plourde@unbc.ca and the Editor-in-Chief, Dr. Derek J. McPhee, E-mail: mcphee@mdpi.org. The subject title of the message should be "Manuscript for Special Issue on Sprirocompounds". Deadline for article submission: 30 July 2008 (Papers can be continuously submitted, processed, and if accepted, continuously published). http://www.mdpi.com/1420-3049/13/11/2848/ The configurational and conformational behavior of some new 3,3,9,9-tetrasubstituted-2,4,8,10-tetraoxaspiro[5.5]undecane derivatives with axial chirality was investigated by conformational analysis and variable temperature NMR experiments. http://www.mdpi.com/1420-3049/13/11/2848/ Mon, 17 Nov 2008 00:00:00 CET Molecules 2008-11-17 13 11 Article 2848 2858 1420-3049 Synthesis and Structure of New 3,3,9,9-Tetrasubstituted-2,4,8,10-Tetraoxaspiro[5.5]undecane Derivatives 2008-11-17 doi: 10.3390/molecules13112848 Alin Mihiş Eric Condamine Elena Bogdan Anamaria Terec Tibor Kurtán Ion Grosu http://www.mdpi.com/1420-3049/13/10/2570/ Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect. http://www.mdpi.com/1420-3049/13/10/2570/ Fri, 17 Oct 2008 00:00:00 CEST Molecules 2008-10-17 13 10 Review 2570 2600 1420-3049 Recent Synthetic Approaches Toward Non-anomeric Spiroketals in Natural Products 2008-10-17 doi: 10.3390/molecules13102570 Sylvain Favre Pierre Vogel Sandrine Gerber-Lemaire http://www.mdpi.com/1420-3049/13/10/2385/ A re-examination of cuticular components of Heliotropium filifolium allowed the isolation of four new compounds: 3’-hydroxy-2’,2’,6’-trimethyl-3H-spiro[1-benzo-furan-2,1’-cyclohexane]-5-carboxylic acid(2), methyl 3’-acetyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (3), methyl 3’-isopentanoyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (4) and methyl 3’-benzoyloxy-2’,2’,6’-trimethyl-3H-spiro[1-benzofuran-2,1’-cyclohexane]-5-carboxylate (5).Compounds 2-5 were identified by their spectroscopic analogies with filifolinol (1), and their structures confirmed by chemical correlation with 1. The antimicrobial properties of the compounds were tested against Gram positive and Gram negative bacteria. Some of them proved to be active against Gram positive, but inactive against Gram negative bacteria. In searching for structure-activity relationships from the obtained MIC values, lipophilicity was shown to be an important variable. http://www.mdpi.com/1420-3049/13/10/2385/ Wed, 01 Oct 2008 00:00:00 CEST Molecules 2008-10-01 13 10 Article 2385 2393 1420-3049 Antibacterial Properties of 3 H-Spiro[1-benzofuran-2,1’-cyclohexane] Derivatives from Heliotropium filifolium 2008-10-01 doi: 10.3390/molecules13102385 Alejandro Urzúa Javier Echeverría Marcos C. Rezende Marcela Wilkens http://www.mdpi.com/1420-3049/13/9/2260/ This review reports on the main results of a set of kinetic elucidation methods developed by our team over the last few years. Formalisms, procedures and examples to solve all possible AB photochromic and thermophotochromic kinetics are presented. Also, discussions of the operating conditions, the continuous irradiation experiment, the spectrokinetic methods testing with numerical integration methods, and the identifiability/distinguishability problems, are included. http://www.mdpi.com/1420-3049/13/9/2260/ Thu, 25 Sep 2008 00:00:00 CEST Molecules 2008-09-25 13 9 Review 2260 2302 1420-3049 Useful Spectrokinetic Methods for the Investigation of Photochromic and Thermo-Photochromic Spiropyrans 2008-09-25 doi: 10.3390/molecules13092260 Mounir Maafi http://www.mdpi.com/1420-3049/13/8/1942/ Spiroketals are widely found as substructures of many naturally occurring compounds from diverse sources including plants, animals as well as microbes. Naturally occurring spiroketals are biologically active and most of them are chiral molecules. This article aims at reviewing the asymmetric synthesis of biologically active spiroketals for last 10 years (1998-2007). http://www.mdpi.com/1420-3049/13/8/1942/ Thu, 28 Aug 2008 00:00:00 CEST Molecules 2008-08-28 13 8 Review 1942 2038 1420-3049 Asymmetric Synthesis of Naturally Occuring Spiroketals 2008-08-28 doi: 10.3390/molecules13081942 B. Rama Raju Anil K. Saikia http://www.mdpi.com/1420-3049/13/8/1840/ This paper describes a synthetic approach to a novel D-glucose-conjugated 15-crown-5 ether having a spiroketal structure starting from a 1-C-vinylated glucose derivative. The approach consists of the glycosylation of the vinylated glucose derivative to give an ethyleneoxy spacer derivative using bismuth(III) triflate, the conversion of the 1-C-vinyl group of the glucoside produced into a carboxylic acid group, and the intramolecular condensation between the carboxyl group and the terminal hydroxyl group in the ethyleneoxy spacer. A D-glucose-conjugated 15-crown-5 ether having a unique spiroketal structure was thus successfully synthesized. http://www.mdpi.com/1420-3049/13/8/1840/ Fri, 22 Aug 2008 00:00:00 CEST Molecules 2008-08-22 13 8 Article 1840 1845 1420-3049 Synthesis of a Novel D-Glucose-Conjugated 15-Crown-5 Ether with a Spiro Ketal Structure 2008-08-22 doi: 10.3390/molecules13081840 Takashi Yamanoi Yoshiki Oda Hitomi Muraishi Sho Matsuda http://www.mdpi.com/1420-3049/13/8/1743/ A set of new bis-spirofused 1,2,4-trioxanes 4a-d was obtained from the reaction of cyclohexane-1,4-dione with allylic hydroperoxides 2a-d, bearing an additional hydroxy group in the homoallylic position, by diastereoselective photooxygenation of allylic alcohols 1a-d and subsequent BF3-catalyzed peroxyacetalization with the diketone. From the reaction of a monoprotected cyclohexane-1,4-dione 5 with the allylic hydroperoxide 6 derived from the singlet oxygenation of methyl hydroxytiglate, one monospiro compound was obtained, the 1,2,4-trioxane ketone 7, as well as a mixture of the diastereoisomeric syn- and anti bis-1,2,4-trioxanes 8. The structures of bis-1,2,4-trioxanes were examined theoretically by DFT methods and compared with X-ray structural data in order to evaluate the preferential trioxane ring conformational orientation. http://www.mdpi.com/1420-3049/13/8/1743/ Tue, 19 Aug 2008 00:00:00 CEST Molecules 2008-08-19 13 8 Article 1743 1758 1420-3049 1,2,5,10,11,14-Hexaoxadispiro[5.2.5.2]hexadecanes: Novel Spirofused Bis-Trioxane Peroxides 2008-08-19 doi: 10.3390/molecules13081743 Axel G. Griesbeck Lars-Oliver Höinck Johann Lex Jörg Neudörfl Dirk Blunk Tamer T. El-Idreesy http://www.mdpi.com/1420-3049/13/8/1640/ Di-D-fructose dianhydrides (DFAs) comprise a unique family of stereoisomeric spiro-tricyclic disaccharides formed upon thermal and/or acidic activation of sucroseand/ or D-fructose-rich materials. The recent discovery of the presence of DFAs in food products and their remarkable nutritional features has attracted considerable interest from the food industry. DFAs behave as low-caloric sweeteners and have proven to exert beneficial prebiotic nutritional functions, favouring the growth of Bifidobacterium spp. In the era of functional foods, investigation of the beneficial properties of DFAs has become an important issue. However, the complexity of the DFA mixtures formed during caramelization or roasting of carbohydrates by traditional procedures (up to 14 diastereomeric spiroketal cores) makes evaluation of their individual properties a difficult challenge. Great effort has gone into the development of efficient procedures to obtain DFAs in pure form at laboratory and industrial scale. This paper is devoted to review the recent advances in the stereoselective synthesis of DFAs by means of chemical and enzymatic approaches, their scope, limitations, and complementarities. http://www.mdpi.com/1420-3049/13/8/1640/ Tue, 12 Aug 2008 00:00:00 CEST Molecules 2008-08-12 13 8 Review 1640 1670 1420-3049 Chemical and Enzymatic Approaches to Carbohydrate-Derived Spiroketals: Di-D-Fructose Dianhydrides (DFAs) 2008-08-12 doi: 10.3390/molecules13071640 M. Isabel García-Moreno Juan M. Benito Carmen Ortiz Mellet José M. García Fernández http://www.mdpi.com/1420-3049/13/6/1282/ Meisenheimer complexes are important intermediates in Nucleophilic Aromatic Substitution Reactions (SNAr). They are formed by the addition of electron rich species to polynitro aromatic compounds or aromatic compounds with strong electron withdrawing groups. It is possible to distinguish two types of Meisenheimer or σ-complexes, the σHcomplex or σX-complex (also named ipso), depending on the aromatic ring position attacked by the nucleophile (a non-substituted or substituted one, respectively). Special examples of σX- or ipso-complexes are formed through intermediate spiro adducts, via intramolecular SNAr. Some of these spirocyclic Meisenheimer complexes, a type of σXcomplex, are exceptionally stable in solution and/or as solids. They can be isolated and characterized using X-ray, and various spectroscopic techniques such as NMR, UV-Vis, IR, and fluorescence. A few of these stable spirocyclic Meisenheimer complexes are zwitterionic and exhibit interesting photophysical and redox properties. We will review recent advances, synthesis and potential applications of these stable spirocyclic Meisenheimer complexes. http://www.mdpi.com/1420-3049/13/6/1282/ Mon, 09 Jun 2008 00:00:00 CEST Molecules 2008-06-09 13 6 Review 1282 1302 1420-3049 Stable Spirocyclic Meisenheimer Complexes 2008-06-09 doi: 10.3390/molecules13061282 Rabih O. Al-Kaysi Iluminada Gallardo Gonzalo Guirado http://www.mdpi.com/1420-3049/13/6/1246/ Density Functional Theory (DFT) calculations have been performed on the TTC→TTT isomerization reaction of the open forms of the 1',3'-dihydro-8-bromo-6-nitro- 1',3',3'-trimethylspiro[2H-1-benzopyran-2,2'-(2H)indole (8-Br-6-nitro-BIPS) system. The calculations were carried out in vacuo and in methylene chloride solution at different temperatures. Results are compared with the available experimental values of free energy difference and activation energy in solution. http://www.mdpi.com/1420-3049/13/6/1246/ Tue, 03 Jun 2008 00:00:00 CEST Molecules 2008-06-03 13 6 Article 1246 1252 1420-3049 Density Functional Theory Study of the Trans-Trans-Cis (TTC)→Trans-Trans-Trans (TTT) Isomerization of a Photochromic Spiropyran Merocyanine 2008-06-03 doi: 10.3390/molecules13061246 Grazia Cottone Rosina Noto Gianfranco La Manna http://www.mdpi.com/1420-3049/13/4/995/ The novel 3H-spiro[1-benzofuran-2-cyclopentan]-3-one skeleton has been madeaccessible by different routes. One- and two-step protocols lead to tricyclic and tetracyclicbenzofuranones 2 and 3, respectively. A four-step synthesis to spirocompound 4 isdescribed. The novel spirocyclic benzofuranones display modest to no inhibition of thehuman peptidyl prolyl cis/trans isomerase Pin1. http://www.mdpi.com/1420-3049/13/4/995/ Tue, 29 Apr 2008 00:00:00 CEST Molecules 2008-04-29 13 4 Article 995 1003 1420-3049 Novel Spiroannulated 3-Benzofuranones. Synthesis and Inhibition of the Human Peptidyl Prolyl cis/trans Isomerase Pin1 2008-04-29 doi: 10.3390/molecules13040995 Manfred Braun Anahita Hessamian-Alinejad Boris Féaux de Lacroix Birte Hernandez Alvarez Gunter Fischer http://www.mdpi.com/1420-3049/13/3/678/ We have synthetized medium-sized cyclophanes and macrocycles containingphosphonic groups, directly linked to the aromatic rings of the phanes or as pendant arms,for use as specific receptors for the selective complexation of neutral guests or forcomplexing lanthanides, as luminescent sensors and for diagnostic bioassays in medicine.Furthermore, because it would be of great interest for biochemistry as well as forpharmacological studies to dispose of preorganized rigid chiral hosts for biorelevantmolecules we designed inter alia, some new chiral macrocycles capable of a triple bindingmode and we used them for constructing macrocycles that could also be of interest forchiral recognition and chiral separations. Thus, in this paper we shall review the salientaspects of some macrocycles synthetized in our laboratory, all possessing the phosphonatemoiety and a spirobisindanol scaffold and able to act as complexing agents for cations andorganic substrates. In particular, we shall describe their NMR characterization, theirstereochemistry in solution and in the solid state, and their use as chiral receptors forbiorelevant molecules. Chiral HPLC resolution of some of them is also reported. http://www.mdpi.com/1420-3049/13/3/678/ Thu, 20 Mar 2008 00:00:00 CET Molecules 2008-03-20 13 3 Review 678 700 1420-3049 New Cleft-like Molecules and Macrocycles from Phosphonate Substituted Spirobisindanol 2008-03-20 doi: 10.3390/molecules13030678 Giuseppe A. Consiglio Salvatore Failla Paolo Finocchiaro http://www.mdpi.com/1420-3049/13/2/405/ Euphorbia wallichii of the family Euphorbiaceae yielded a new rearrangedpentacyclic triterpene of the multiflorane class which we have named spirowallichiione.The structure of this natural spirocompound was elucidated with the aid of modernspectroscopic techniques, including 2D-NMR. http://www.mdpi.com/1420-3049/13/2/405/ Mon, 18 Feb 2008 00:00:00 CET Molecules 2008-02-18 13 2 Article 405 411 1420-3049 Spirowallichiione: A Rearranged Multiflorane from Euphorbia wallichii Hook F. (Euphorbiaceae) 2008-02-18 doi: 10.3390/molecules13020405 Muhammad Shaiq Ali Shakeel Ahmed Muhammad Saleem http://www.mdpi.com/1420-3049/13/2/331/ 2-Acetylcyclopentanone undergoes a smooth reaction with triphenylphosphineand dialkyl acetylenedicarboxylates to produce dialkyl 2-(1-acetyl-2-oxocyclopentyl)-3-(1,1,1-triphenyl-λ5-phosphanylidene)succinates. These compounds undergo intramolecularWittig reactions in boiling benzene to produce highly strained spirocyclobutenederivatives, which spontaneously undergo ring-opening reactions to produce dialkyl (E)-2-[1-(2-oxocyclopentyliden)ethyl]-2-butenedioates. http://www.mdpi.com/1420-3049/13/2/331/ Thu, 07 Feb 2008 00:00:00 CET Molecules 2008-02-07 13 2 Article 331 339 1420-3049 A Facile Route to Diastereomeric Phosphorus Ylides. Chemoselective Synthesis of Dialkyl (E)-2-[1-(2-Oxocyclopentylidene)ethyl]-2-butenedioates 2008-02-07 doi: 10.3390/molecules13020331 Sakineh Asghari Mohammad Bagher Poushani Samaneh Ramezani http://www.mdpi.com/1420-3049/13/2/319/ Nitroalkanes can be profitably employed as carbanionic precursors for theassembly of dihydroxy ketone frameworks, suitable for the preparation of spiroketals. Thecarbon-carbon bond formation is carried out exploiting nitroaldol and Michael reactions,while the nitro to carbonyl conversion (Nef reaction) ensures the correct introduction of theketo group. Several spiroketal systems endowed with considerable biological activity canbe prepared using this synthetic strategy. http://www.mdpi.com/1420-3049/13/2/319/ Thu, 07 Feb 2008 00:00:00 CET Molecules 2008-02-07 13 2 Review 319 330 1420-3049 Nitroalkanes as Central Reagents in the Synthesis of Spiroketals 2008-02-07 doi: 10.3390/molecules13020319 Roberto Ballini Marino Petrini Goffredo Rosini