Exploring New Chemical Space by Stereocontrolled Diversity-Oriented Synthesis  Prabhat Arya, Reni Joseph, Zhonghong Gan, Bojana Rakic  Chemistry & Biology  Volume 12, Issue 2, Pages 163-180 (February 2005) DOI: 10.1016/j.chembiol.2005.01.011 Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 1 Kapoor and Coworkers’ Solid-Phase Synthesis of HR22C16 Analogs that Utilized a Stereocontrolled Pictet-Spengler Approach Taken from the article by Hotha et al. [30]. (A) Schematic representation of the assay. Vertebrate cells (BS-C-1) in multiwell plates are stained for the actin cytoskeleton and are imaged from below by using a 4× objective. (B) The effect of a compound that causes no morphological change. (C and D) (C) The effect of HR22C16 and (D) the configuration of microtubules in a (left) control cell and a (right) HR22C16-treated cell. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 2 Application of a Domino Reaction Combined with Enantioselective Hydrogenation to Obtain Emetine Analogs by Tietze and Coworkers See [31]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 3 Waldmann and Coworkers’ Solid-Phase Synthesis of Dysidiolide-Derived Protein Phosphatase Inhibitors See [32]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 4 Takahashi and Coworkers’ Solid-Phase Approach to Vitamin D3 See [33, 34]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 5 Myers and Coworkers’ Enantioselective Solid-Phase Synthesis of Saframycin Analogs See [36, 37]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 6 Bioactive Spiroketal Moieties Embedded in Spongistatin and Okadaic Acid Waldmann and coworkers’ [40] enantioselective, aldol-based solid-phase synthesis of the spiroketal library. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 7 Schreiber and Coworkers’ DOS Approach to Obtain Skeletally Diverse Natural Product-like Compounds See [43]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 8 Schreiber and Coworkers’ Approach to 2H-Pyran Derivatives (A) An application of enantioselective Lewis acid catalysis on solid phase to obtain a library of substituted 2H-pyrans. (B) Small-molecule microarray of compounds obtained from a substituted 2H-pyran library (taken from [46]). See [45, 46]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 9 Schreiber and Coworkers’ Approach (A) A library of small molecules containing atrop-diastereodefined, medium-sized rings. (B) (a and b) Plant and (c and d) Zebrafish assay: (a) 7-day-old Arabidopsis seedlings germinated on agar containing 1% DMSO and a small-molecule library member (10 μm). (b) 7-day-old control experiment. (c) Synchronized Zebrafish embryos upon treatment with a small-molecule library member (100 nM); these embryos are slow to develop, and they exhibit lower than normal pigmentation, weak hearts, abnormal brains, and misshapen jaws. (d) Synchronized embryos upon treatment with the same library member (5 μm); Zebrafish look indistinguishable from untreated controls (taken from [48]). See [47, 48]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 10 Schreiber and Coworkers’ Boronic Ester Annulation/Diels-Alder Approach See [49, 50]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 11 Schreiber and Coworkers’ DOS Approach to Obtain Polycyclic Compounds from Glycals See [51]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 12 An Asymmetric Cycloaddition Approach by Schreiber and Coworkers (A) A cycloaddition approach with triene to obtain polycyclic compounds. (B) An approach to immobilize small molecules having an acidic proton on an aminopropyl glass surface by Schreiber and coworkers. (C) Few library members identified as Calmodulin protein binding agents. See [55, 57]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 13 An Application of Immobilized Dihydroisoquinoline to Obtain Skeletally Different Compounds See [60]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 14 Arya and Coworkers’ Stereocontrolled DOS to Obtain Tetrahydroquinoline-Derived, Natural Product-like, Polycyclic Compounds See [60]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 15 Ring-Closing Metathesis Approach by Arya and Coworkers (A) RCM approach to obtain natural product-like, polycyclic compounds. (B) Regio- and stereoselective hetero-Michael approach to tetrahydroquinoline-based, polycyclic compounds. (C) Stereocontrolled solid-phase synthesis of tetrahydroquinoline-based, natural product-like, polycyclic compounds. See [60]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 16 Stereocontrolled Diversity-Oriented Reactions (A) Tetrahydroquinoline-derived, polycyclic compounds having a functionalized 8-membered ring. (B) Ring conformation-controlled, asymmetric conjugate addition. See [61]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions

Figure 17 Natural Product-like Compounds with a Bridged, Medium-Sized Ring (A) Tetrahydroquinoline-based polycyclics having a functionalized, bridged, 10-membered ring. (B) Solid-phase synthesis of tetrahydroquinoline-based, polycyclic compounds with a bridged, 10-membered ring. See [66]. Chemistry & Biology 2005 12, 163-180DOI: (10.1016/j.chembiol.2005.01.011) Copyright © 2005 Elsevier Ltd Terms and Conditions