Roberto Ballini 1,*, Marino Petrini 1 and Goffredo Rosini 2
1 Dipartimento di Scienze Chimiche, Università di Camerino, via S.Agostino, 1, I-62032 Camerino, Italy; E-mail: marino.petrini@unicam.it
2 Dipartimento di Chimica Organica ‘A. Mangini’, Alma Mater Studiorum–Università di Bologna, Viale del Risorgimento n. 4, 40136 Bologna, Italy; E-mail: goffredo.rosini@unibo.it
* Author to whom correspondence should be addressed; E-mail: roberto.ballini@unicam.it; Fax: +39 0737 402297
Received: 8 January 2008; in revised form: 2 February 2008 / Accepted: 4 February 2008 / Published: 7 February 2008
Review: Nitroalkanes as Central Reagents in the Synthesis of Spiroketals
Molecules 2008, 13, 319-330 (PDF format 81 K)
Molecules Manuscript ID: spirocompounds-20071214-Gerber-ch
Type of the paper: Review
Title: Synthetic Approaches toward the Spiroketals Subunits of Spongistatins
Authors: Sandrine Gerber * and Sylvain Favre
ISIC-Direction, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC, Station 6
CH-1015 Lausanne, Switzerland
Laboratoire de Glycochimie et Synthèse Asymétrique
Tel : +41 21 693 93 72, Fax: +41 21 693 93 55; E-mail: sandrine.gerber@epfl.ch
http://isic2.epfl.ch/page59148.htlm
Abstract: Spiroketals and in particular 6,6-congeners are key structural features of a variety of natural products of biological interest. In particular, spongistatins (altohyrtins), which have been isolated in 1993 by three research groups from marine sponges of the genus Spongia, present two highly functionalized 6,6-spiroketal subunits in their skeleton. These molecules were found to be among the most potent cancer cells growth inhibitors tested to date by the U.S. National Cancer Institute on a panel of 60 human carcinoma cell lines, with GI50 values in the nanomolar and picomolar ranges. Despite these promising properties, further biological investigations were precluded by the extremely low quantities that can be obtained by extraction of marine organisms and the unacceptable ecological impact of larger scale isolation of the producing sponges. This scarce abundance, combined with remarkable structural complexity, prompted many research groups to address the challenge of the synthesis of these macrolides. Several total syntheses have been reported and many routes to key subunits have also been described. In particular, considerable efforts have been devoted to the efficient preparation of the axial / axial AB and axial / equatorial CD spiroketals and on the EF tetrahydropyran fragment. In this review we shall concentrate on the various approches that have been reported toward the efficient delivery of the spiroketals fragments of spongistatins and on their assembly. The biological activity of these macrolides will also be discussed.
Molecules Manuscript ID: spirocompounds-20071213-Saikia-in
Type of the paper: Review
Title: Asymmetric Synthesis of Naturally Occurring Spiroketals
Authors: B. Rama Raju and Anil K. Saikia
E-mail: asaikia@iitg.ernet.in
Abstract: 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).
Molecules Manuscript ID: spirocompounds-20080109-Benito-es
Type of the paper: Review
Title: Chemical and Enzymatic Approaches to Carbohydrate-Derived Spiroketals: Di-D-Fructose Dianhydrides (DFAs)
Authors: Carmen Ortiz Mellet,1 José M. García Fernández,2 M. Isabel García Moreno,1,* and Juan M. Benito2,*
1 Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain
2 Instituto de Investigaciones Químicas, CSIC – Universidad de Sevilla, Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain
Tel : +34 954559997, Fax: +34 954624960; E-mail: isagar@us.es; Tel : +34 954489560, Fax: +34 954460565; E-mail: juanmab@iiq.csic.es
Abstract: Di-D-fructose dianhydrides (DFAs) comprise a unique family of stereoisomeric spiro-tricyclic disaccharides formed upon thermal and/or acidic activation of sucrose- and/or D-fructose-rich materials. The recent discovery of the presence of DFAs in food products and their remarkable nutritional features have considerably attracted the interest of 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 DFAs becomes 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 investigation of their individual properties a difficult challenge. A great effort has been put forward to develop 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.
Molecules Manuscript ID: spirocompounds-20080117-Finocchiaro-it
Type of the paper: Review
Title: New Clefts-like Molecules and Macrocycles from Phosponate Substituted Spriobisindanol
Authors: Giuseppe A.Consiglio, Salvatore Failla and Paolo Finocchiaro
Dipartimento di Metodologie fisiche e chimiche per l`ingegneria, Università di Catania, Viale A. Doria , 6-95125-Catania Italy
E-mail: pfinocchiaro@dmfci.unict.it
Abstract: The spirobisindanol phosphonate unit (I) which possesses a C2 rigid conformation is a new building block that we used for the synthesis of cleftlike and small chiral cyclic receptor molecules containing the phosphonates groups and fully equipped for multipoint binding of basic amino acids (Lys,Arg,His,Lys) possessing relevant biological interest. Furthermore by using compound (I) we prepared a lot of different chiral macrocyclic receptor molecules possessing conformational mobility in solution and able to clathrate small organic neutral guests as well to achieve enantioselective and strong recognition of basic amino acids in water. Reacting I with 1,2,4,5-tetrakisbromethylbenzene, according to the Williamson condensation, we produced a new chiral macrobicyclic compound, in which a benzene ring is positioned in the center of a pair of extended chiral cyclophane frames in a molecular equivalent of a “hamburger”and the phosphonate groups are in external strategical positions for complexation. Among the possible diastereomers possible, after the cyclization process we isolted two of them and the structure of all compounds were assigned by 1H and 13C NMR, as well by mass spectrometry. Thus, in this paper we shall report on the synthesis, stereochemical characterization in solution and clathration properties of different cyclophanes and macrocycles containing the spirobisindanol moiety as well the elucidation by X-ray diffraction methods of the preferred geometry adopted by some of these compounds in the solid state. In addition, we shall report the syntheses of new phosphonated derivatives of bis-indanol, that can be used in order to reduce the flammability of thermosetting DGEBA epoxy resin and other polycondensates of commercial relevance and we will describe the photophysical properties of new Ln(III) complexes with cyclophanes containing spirobiindanol phosphonates derivatives in different media.
Molecules Manuscript ID: spirocompounds-20080130-Maafi-uk
Type of the paper: Review
Title: Spectrokinetic Methods for the Investigation of Photochromic and Thermo-Photochromic Spiropyrans
Authors: Mounir Maafi MMaafi@dmu.ac.uk
E-mail: MMaafi@dmu.ac.uk
Abstract: In this review the principal results of the most recent spectrokinetic methods, developed for the elucidation and quantification of the photo- and thermo-photochromism of spiropyrans and similar compounds, are discussed. The methods address the transformation between the initial spiropyran species (the closed form) and its merocyanine isomer (the coloured form) which can be governed by kinetics involving up to four steps (namely two photochemical and two thermal reactions). An elucidation of each kinetic case is presented here in a simple-to-implement and
easy-to-use procedure, based on a minimum set of kinetic data. Such reliable tools can be relevant to extend and sustain the development of new spiropyran derivatives that carry the specific properties required for a number of technologically important applications.
Molecules Manuscript ID: spirocompounds-20080209-Guirado-es
Type of the paper: Review
Title: Stable Spirocyclical Meisenheimer Complexes
Authors: Rabih O. Al-Kaysi 1,*, Iluminada Gallardo2 and Gonzalo Guirado2,*
1 King Saud Bin Abdulaziz University for Health Sciences. National Guard-Health Affairs.
Mail Building Code 1150. Riyadh 11423. Kingdom of Saudi Arabia. Phone: (966)-5-61429528 ; Email: kaysir@ksau-hs.edu.sa
2Departament de Química, Universitat Autònoma de Barcelona, 08193-Bellaterra, Barcelona, Spain; Phone: (+ ) 00 34 93 581 48 82; Fax: (+) 00 34 93 581 29 20
E-mail: Iluminada.Gallardo@uab.es ; Gonzalo.Guirado@uab.es
* Author to whom correspondence should be addressed. (Apply M_address)
Abstract: Meiseheimer complexes are important intermediates in Nucleophilic Aromatic Substitution Reaction (SNAr) formed by the addition of electron rich species to polynitoraromatic compounds or aromatic compounds with strong electron withdrawing groups. It is possible to distinguish two types of Meisenheimer or σ-complexes, the σH-complex or σX-complex (also named ipso), depending on the aromatic ring position attacked by the nucleophile (a non-substituted or substituted one, respectively). A special case of σX- or ipso-complexes are formed through intermediate spiro adducts, via intramolecular SNAr. Some of these spirocyclical Meisenheimer or sX-complexes are exceptionally stable in solution and/or as solids. They can be isolated and characterized using X-ray, and various spectroscopical techniques such as NMR, UV-vis, IR, and fluorescence. However, only a few of these stable spirocyclical Meisenheimer complexes are zwitterionic and exhibit interesting photophysical and redox properties. This manuscript will review recent advances, scope and potential applications of these stable spirocyclical Meisenheimer complexes.
