A new and informative [a,b,c,d] nomenclature for one-pot multistep transformations: a simple tool to measure synthetic efficiency

Domino, cascade and tandem reactions constitute the most efficient and creative chemical transformations with a huge domain of synthetic utility and applications. A number of reactions may be achieved in a single pot, accompanied by the formation of new rings and new bonds, leading towards higher molecular complexity. A lack of one unified, yet informative descriptor often understates the synthetic ingenuity of certain highly creative transformations. In this review, we propose a new tetra-coordinated [a,b,c,d] nomenclature which takes into account and displays the basic parameters which generally indicate the level of efficiency of a chemical transformation. An almost exhaustive set of one-pot multistep reactions may be described by this system and this review is an attempt to display the one-pot multistep transformations reported from our group and to classify them based on our proposed descriptor.

[1]  Yujiro Hayashi,et al.  Pot economy and one-pot synthesis , 2016, Chemical science.

[2]  F. Nicotra.  SYNTHESIS OF C-GLYCOSIDES OF BIOLOGICAL INTEREST , 1997 .

[3]  Toshihiro Nishimura,et al.  An Asymmetric Synthesis of the Fully Functionalized AB Ring System of 12-Demethyltaxol via Successive Stereoselective Allylation and Intramolecular Aldol Reactions , 1995 .

[4]  R Scott Obach,et al.  Biotransformation reactions of five-membered aromatic heterocyclic rings. , 2002, Chemical research in toxicology.

[5]  B. B. Mishra,et al.  Cu-Catalyzed Click Reaction in Carbohydrate Chemistry. , 2016, Chemical reviews.

[6]  P. Evans,et al.  A Concise, Efficient and Scalable Total Synthesis of Thapsigargin and Nortrilobolide from (R)-(-)-Carvone. , 2017, Journal of the American Chemical Society.

[7]  D. Venkataraman,et al.  Synthesis of 2-arylbenzo[b]furans via copper(I)-catalyzed coupling of o-iodophenols and aryl acetylenes. , 2002, Organic Letters.

[8]  J. Rohr,et al.  ANGUCYCLINES : TOTAL SYNTHESES, NEW STRUCTURES, AND BIOSYNTHETIC STUDIES OF AN EMERGING NEW CLASS OF ANTIBIOTICS , 1997 .

[9]  M. Dubois,et al.  Palustroside, a coumarin glucoside ester fromLedum palustre , 1990 .

[10]  Mobin M. Shaikh,et al.  A tandem enyne/ring closing metathesis approach to the synthesis of novel angularly fused dioxa-triquinanes , 2006 .

[11]  T. Hosoya,et al.  Total synthesis of the gilvocarcins , 1994 .

[12]  P. Wender,et al.  New reactions and step economy: the total synthesis of (±)-salsolene oxide based on the type II transition metal-catalyzed intramolecular [4 + 4] cycloaddition , 2006 .

[13]  W. Roush,et al.  Enantioselective Total Synthesis of (−)-Chlorothricolide via the Tandem Inter- and Intramolecular Diels−Alder Reaction of a Hexaenoate Intermediate , 1998 .

[14]  H. Kolb,et al.  The growing impact of click chemistry on drug discovery. , 2003, Drug discovery today.

[15]  S. S. Garrido,et al.  A 4.2 kDa synthetic peptide as a potential probe to evaluate the antibacterial activity of coumarin drugs , 2004, Journal of peptide science : an official publication of the European Peptide Society.

[16]  J. Lytton,et al.  Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. , 1991, The Journal of biological chemistry.

[17]  J. Bode,et al.  Catalytic selective synthesis. , 2012, Angewandte Chemie.

[18]  W. Roush,et al.  Enantioselective Total Synthesis of (-)-Chlorothricolide , 1994 .

[19]  Barry M. Trost,et al.  Atom Economy—A Challenge for Organic Synthesis: Homogeneous Catalysis Leads the Way , 1995 .

[20]  S. Hecht,et al.  Luotonin A. A naturally occurring human DNA topoisomerase I poison. , 2003, Journal of the American Chemical Society.

[21]  J. Moses,et al.  The growing applications of click chemistry. , 2007, Chemical Society reviews.

[22]  S. P. Andrews,et al.  Total synthesis of thapsigargin, a potent SERCA pump inhibitor. , 2007, Organic letters.

[23]  T. Nishikawa.  Synthesis of a α-C-Mannosyltryptophan Derivative, Naturally Occurring C-Glycosyl Amino Acid Found in Human Ribonuclease , 1999 .

[24]  B. Trost,et al.  The atom economy--a search for synthetic efficiency. , 1991, Science.

[25]  N. Jacobsen,et al.  Synthesis and insecticidal properties of derivatives of propane‐1, 3‐dithiol (analogues of the insecticidal derivatives of dithiolane and trithiane from the alga Chara globularis Thuillier) , 1983 .

[26]  Vishwakarma Singh,et al.  Hybrid systems through natural product leads: an approach towards new molecular entities. , 2002, Chemical Society reviews.

[27]  Chemoselective catalytic conjugate addition of alcohols over amines. , 2014, Angewandte Chemie.

[28]  Parthasarathi Subramanian,et al.  A One‐Pot, Copper‐Catalyzed Cascade Route to 2‐Indolyl‐C‐glycosides , 2013 .

[29]  L. Tietze,et al.  Sequential Transformations in Organic Chemistry: A Synthetic Strategy with a Future† , 1993 .

[30]  Michal Hocek,et al.  Modular synthesis of 1-α- and 1-β-(indol-2-yl)-2'-deoxyribose C-nucleosides. , 2011, Organic & biomolecular chemistry.

[31]  S. Harikrishna,et al.  Influence of 2'-fluoro versus 2'-O-methyl substituent on the sugar puckering of 4'-C-aminomethyluridine. , 2013, The Journal of organic chemistry.

[32]  H. Togo,et al.  Application of the versatile character of the tellurium atom for the synthesis of C-nucleoside analogues via sugar tellurides , 1998 .

[33]  K. Kakiuchi,et al.  A new route for the construction of the AB-ring core of Taxol , 2003 .

[34]  L. Tietze.  Domino Reactions in Organic Synthesis. , 1996, Chemical reviews.

[35]  K. Kaliappan,et al.  A cascade enyne/ring closing metathesis approach to angularly fused dioxatriquinanes. , 2004, Chemical communications.

[36]  J. T. Njardarson,et al.  Evolution of an oxidative dearomatization enabled total synthesis of vinigrol. , 2014, Organic & biomolecular chemistry.

[37]  J. N. Johnston,et al.  To protonate or alkylate? Stereoselective Brønsted acid catalysis of C-C bond formation using diazoalkanes. , 2010, Angewandte Chemie.

[38]  K C Nicolaou,et al.  Cascade reactions in total synthesis. , 2006, Angewandte Chemie.

[39]  S. Chandrasekhar,et al.  Inter and intramolecular copper(I)-catalyzed 1,3-dipolar cycloaddition of azido-alkynes: synthesis of furanotriazole macrocycles ☆ , 2007 .

[40]  I. S. Aidhen,et al.  Umpolung strategy for the synthesis of 2-deoxy-C-aryl glycosides: a serendipitous, efficient route for C-furanoside analogues. , 2002, Organic letters.

[41]  A. Da Settimo,et al.  Synthesis, in vitro antiproliferative activity and DNA-interaction of benzimidazoquinazoline derivatives as potential anti-tumor agents. , 2001, Farmaco.

[42]  K. Kaliappan,et al.  ‘Click’ Chemistryon Sugar-Derived Alkynes: A Tandem ‘Click-Click’ Approachto Bistriazoles , 2009 .

[43]  Parthasarathi Subramanian,et al.  A Unified Strategy Towards N‐Aryl Heterocycles by a One‐Pot Copper‐Catalyzed Oxidative C–H Amination of Azoles , 2014 .

[44]  P. Baran,et al.  Modern synthetic efforts toward biologically active terpenes. , 2007, Nature chemical biology.

[45]  D. Hockless,et al.  From Toluene to TaxolTM: Chemoenzymatic and Enantiodivergent Routes to the AB-Ring Systems of Taxoids and ent-Taxoids , 1998 .

[46]  K. Kaliappan,et al.  A facile domino metathetic route to a thapsigargin skeleton. , 2005, Organic & biomolecular chemistry.

[47]  S. P. Andrews,et al.  Total synthesis of five thapsigargins: guaianolide natural products exhibiting sub-nanomolar SERCA inhibition. , 2007, Chemistry.

[48]  R. Handschumacher,et al.  Clinical, Biological, and Biochemical Effects of Pyrazofurin , 1978 .

[49]  Phil S. Baran,et al.  The economies of synthesis. , 2009, Chemical Society reviews.

[50]  M. Mckee,et al.  Synthesis of C-Saccharides and Higher Congeners , 2001 .

[51]  Young-Gi Lee,et al.  New Click Chemistry: Polymerization Based on 1,3-Dipolar Cycloaddition of a Homo Ditopic Nitrile N-Oxide and Transformation of the Resulting Polymers into Reactive Polymers , 2009 .

[52]  H. Togo,et al.  Strategic approach to C-nucleosidesvia sugar anomeric radical, cation, and anion with sugar tellurides , 1997 .

[53]  K. Nicolaou,et al.  The endiandric acid cascade. Electrocyclizations in organic synthesis. 3. "Biomimetic" approach to endiandric acids A-G. Synthesis of precursors , 1982 .

[54]  C. Heathcock,et al.  Daphniphyllum alkaloids. Part 5. Total synthesis of (.+-.)-daphnilactone A: a novel fragmentation reaction , 1989 .

[55]  Guangbin Dong,et al.  Divergent syntheses of fused β-naphthol and indene scaffolds by rhodium-catalyzed direct and decarbonylative alkyne-benzocyclobutenone couplings. , 2014, Angewandte Chemie.

[56]  D. Black,et al.  Postulated electrocyclic reactions leading to endiandric acid and related natural products , 1980 .

[57]  P. Das,et al.  Cope-House Cyclization Strategy for the Synthesis of Pyrrolizidines: An Expedient Route to 5-epi-Hyacinthacine A3 and 5-epi-Hyacinthacine A5 , 2008 .

[58]  H. Pellissier,et al.  Stereocontrolled domino reactions. , 2013, Chemical reviews.

[59]  C. Heathcock,et al.  Daphniphyllum alkaloids. 15. Total syntheses of (.+-.)-methyl homodaphniphyllate and (.+-.)-daphnilactone A , 1992 .

[60]  K. Nicolaou,et al.  The art of total synthesis through cascade reactions. , 2009, Chemical Society reviews.

[61]  S. Christensen,et al.  A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPases. , 1998, Trends in pharmacological sciences.

[62]  D. Levy,et al.  The Chemistry of C-Glycosides , 1995 .

[63]  K. A. Parker,et al.  METHODOLOGY FOR THE REGIOSPECIFIC SYNTHESIS OF BIS C-ARYL GLYCOSIDES. MODELS FOR KIDAMYCINS , 1994 .

[64]  Justin Kim,et al.  Biogenetically inspired syntheses of alkaloid natural products. , 2009, Chemical Society reviews.

[65]  T. Hoye,et al.  Otteliones A and B: Potently cytotoxic 4-methylene-2-cyclohexenones from Ottelia alismoides , 1998 .

[66]  S. Benner,et al.  A Review: Synthesis of Aryl C-Glycosides Via the Heck Coupling Reaction , 2006 .

[67]  K. Nicolaou,et al.  The endiandric acid cascade. Electrocyclizations in organic synthesis. I. Stepwise, stereocontrolled total synthesis of endiandric acids A and B , 1982 .

[68]  Mathias Christmann,et al.  One-pot reactions accelerate the synthesis of active pharmaceutical ingredients. , 2011, Angewandte Chemie.

[69]  Yanguang Wang,et al.  Novel and efficient synthesis of iminocoumarins via copper-catalyzed multicomponent reaction. , 2006, Organic letters.

[70]  R. Nagarajan,et al.  Copper catalysed synthesis of indolylquinazolinone alkaloid bouchardatine , 2014, Journal of Chemical Sciences.

[71]  K. Kaliappan,et al.  Synthetic studies on taxanes: A domino-enyne metathesis/Diels-Alder approach to the AB-ring , 2008 .

[72]  Biao Yu,et al.  Recent Advances in the Chemical Synthesis of C-Glycosides. , 2017, Chemical reviews.

[73]  A. Marra,et al.  C-glycoside clustering on calix[4]arene, adamantane, and benzene scaffolds through 1,2,3-triazole linkers. , 2006, The Journal of organic chemistry.

[74]  R. S. Coleman,et al.  Coumarin base-pair replacement as a fluorescent probe of ultrafast DNA dynamics , 2007 .

[75]  Sushobhan Chowdhury,et al.  Advances of azide-alkyne cycloaddition-click chemistry over the recent decade , 2016 .

[76]  Elisabetta Brenna,et al.  Recent advances in the benzannulation of substituted 3-alkoxycarbonyl-3,5-hexadienoic acids and 3-alkoxycarbonylhex-3-en-5-ynoic acids to polysubstituted aromatics. , 2007, Chemistry.

[77]  M. Isobe,et al.  Stereocontrolled syntheses of α-C-mannosyltryptophan and its analogues , 2005 .

[78]  Parthasarathi Subramanian,et al.  Transition‐Metal‐Catalyzed Selective Cyclization Strategy to 2‐Substituted Benzofurans and Indoles en Route to the Oxa Analogues of Isocryptolepine , 2014 .

[79]  Paul A. Clarke,et al.  Combining pot, atom and step economy (PASE) in organic synthesis. Synthesis of tetrahydropyran-4-ones , 2007 .

[80]  K. Kaliappan,et al.  A new versatile strategy for C-aryl glycosides. , 2007, Organic letters.

[81]  J. T. Njardarson,et al.  Total synthesis of vinigrol. , 2013, Angewandte Chemie.

[82]  K. Kaliappan,et al.  Synthesis of a bicyclo[5.3.1]undecene by a facile domino enyne cross-metathesis/IMDA , 2006 .

[83]  B. Blagg,et al.  Development of novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines. , 2008, The Journal of organic chemistry.

[84]  K. Nicolaou,et al.  The endiandric acid cascade. Electrocyclizations in organic synthesis. 4. Biomimetic approach to endiandric acids A-G. Total synthesis and thermal studies , 1982 .

[85]  K. Kaliappan,et al.  A hybrid approach to new molecular scaffolds , 2013 .

[86]  H. Wagenknecht,et al.  Indole in DNA: Comparison of a Nucleosidic with a Non-Nucleosidic DNA Base Substitution , 2009 .

[87]  R. W. Harper,et al.  Benzimidazo[2,1-b]quinazolin-12-ones. A new class of potent immunosuppressive compounds. , 1971, Journal of medicinal chemistry.

[88]  K. Kaliappan,et al.  Synthesis of a Novel Taxa‐Oxa‐Sugar Hybrid Core Structure by Tandem Cross‐Enyne Metathesis/IMDA , 2010 .

[89]  U. Rasmussen,et al.  On the mechanism of histamine release induced by thapsigargin fromThapsia garganica L. , 1979, Agents and Actions.

[90]  Paul A Wender,et al.  Function-oriented synthesis, step economy, and drug design. , 2008, Accounts of chemical research.

[91]  I. Rodríguez-Meizoso,et al.  A Click Approach to Unprotected Glycodendrimers , 2006 .

[92]  G. Kraus,et al.  A bridgehead carbocation fragmentation leading to the taxane AB ring system , 1993 .

[93]  K. Kaliappan,et al.  A domino enyne/IMDA approach to the core structure of (-) vinigrol. , 2014, Organic letters.

[94]  P. Baran,et al.  Total synthesis of vinigrol. , 2009, Journal of the American Chemical Society.

[95]  S. Hotha,et al.  Expedient synthesis of 1,2,3-triazole-fused tetracyclic compounds by intramolecular Huisgen (‘click’) reactions on carbohydrate-derived azido-alkynes , 2005 .

[96]  Paul A Wender,et al.  Toward the ideal synthesis and molecular function through synthesis-informed design. , 2014, Natural product reports.

[97]  R. S. Coleman,et al.  Synthesis of a Novel Coumarin C-Riboside as a Photophysical Probe of Oligonucleotide Dynamics , 1998 .

[98]  M. Treiman,et al.  Thapsigargin discriminates strongly between Ca2+‐ATPase phosphorylated intermediates with different subcellular distributions in bovine adrenal chromaffin cells , 1995, FEBS letters.

[99]  Guolin Zhang,et al.  Three New Eudesmanolactones (=Eudesmanolides) from Camchaya loloana , 2011 .

[100]  E. De Clercq,et al.  1,2,3-Triazole-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity. , 1994, Journal of medicinal chemistry.

[101]  Zhengren Xu,et al.  Stereocontrolled and efficient total synthesis of (-)-stephanotic acid methyl ester and (-)-celogentin C. , 2010, Organic letters.

[102]  L. Barriault,et al.  A formal synthesis of vinigrol. , 2012, Angewandte Chemie.

[103]  P. Baran,et al.  A concise approach to vinigrol. , 2008, Angewandte Chemie.

[104]  C. K. Chu,et al.  Fluorinated Nucleosides: Synthesis and Biological Implication. , 2008, Journal of fluorine chemistry.

[105]  S. Ley,et al.  A route to the thapsigargins from (S)-carvone providing a substrate-controlled total synthesis of trilobolide, nortrilobolide, and thapsivillosin F. , 2003, Angewandte Chemie.

[106]  A. Yepremyan,et al.  Total synthesis of indole-3-acetonitrile-4-methoxy-2-C-β-D-glucopyranoside. Proposal for structural revision of the natural product. , 2012, Organic & biomolecular chemistry.

[107]  Joel Morris,et al.  Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. , 2000, Journal of medicinal chemistry.

[108]  V. Khilya,et al.  Modified Coumarins. 17. Synthesis and Anticoagulant Activity of 3,4-Cycloannelated Coumarin D-Glycopyranosides , 2005, Chemistry of Natural Compounds.

[109]  Zhenjiang Zhao,et al.  Novel benzo-1,2,3-thiadiazole-7-carboxylate derivatives as plant activators and the development of their agricultural applications. , 2012, Journal of agricultural and food chemistry.

[110]  T. Burke,et al.  Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56lck. , 1993, Journal of medicinal chemistry.

[111]  A. Bonnefoy,et al.  Noviose mimics of the coumarin inhibitors of gyrase B , 2003 .

[112]  S. Natarajan,et al.  Synthesis of a highly functionalised AB taxane ring system: formation of the eight-membered ring by an efficient 8-exo-tet alkylation of an α-sulfonyl anion , 1995 .

[113]  Jean-François Lutz,et al.  1,3-dipolar cycloadditions of azides and alkynes: a universal ligation tool in polymer and materials science. , 2007, Angewandte Chemie.

[114]  G. Qiu,et al.  Novel indole C-glycosides from Isatis indigotica and their potential cytotoxic activity. , 2011, Fitoterapia.

[115]  D. Knight,et al.  On the use of anomeric hydroxylamines in the reverse-Cope cyclisation , 2007 .

[116]  K. Kaliappan,et al.  Stereoselective Synthesis of Trifluoromethyl Analogues of Polyhydroxypyrrolidines , 2013 .

[117]  Takashi Matsumoto,et al.  Total Synthesis of Aryl C-Glycoside Natural Products: Strategies and Tactics. , 2017, Chemical reviews.

[118]  P. Seeberger,et al.  Synthesis of C-aryl and C-alkyl glycosides using glycosyl phosphates. , 2001, Organic Letters.

[119]  Parthasarathi Subramanian,et al.  Copper-Catalyzed Cascade Amination Route to N-Aryl Benzimidazoquinazolinones. , 2016, The Journal of organic chemistry.

[120]  C. NicolaouK,et al.  エンジアンドル酸の流れ(cascade) 有機合成における電子環化反応 II エンジアンドル酸C―Gの段階的,立体制御全合成 , 1982 .

[121]  D. Astruc,et al.  "Click" dendrimers: synthesis, redox sensing of Pd(OAc)2, and remarkable catalytic hydrogenation activity of precise Pd nanoparticles stabilized by 1,2,3-triazole-containing dendrimers. , 2008, Chemistry.

[122]  J. Cha,et al.  Synthetic studies on taxol. Assembly of the bicyclo[5.3.1]undecane moiety (AB ring system) of taxane diterpenes , 1992 .

[123]  Hang Chu,et al.  Scalable Synthesis of (−)-Thapsigargin , 2016, ACS central science.

[124]  L. Zetta,et al.  C-Heteroarylation of sugars by indolylbromomagnesium salts. Synthesis of 3-(alditol-1-yl)indoles and their cyclization to indole C-nucleoside analogs , 1991 .

[125]  S. Chandrasekhar,et al.  Natural product hybrids as new leads for drug discovery. , 2003, Angewandte Chemie.

[126]  Erhong Hao,et al.  Syntheses and Electropolymerization of Carboranyl-Functionalized Pyrroles and Thiophenes , 2007 .

[127]  L. Lee,et al.  New synthesis of 2-alkylpyrrolidines and 2-alkylpiperidines , 1976 .

[128]  V. Singh,et al.  Progress in the construction of cyclooctanoid systems: new approaches and applications to natural product syntheses. , 1999, Chemical reviews.

[129]  A. Marra,et al.  Synthesis of sialoclusters appended to calix[4]arene platforms via multiple azide-alkyne cycloaddition. New inhibitors of hemagglutination and cytopathic effect mediated by BK and influenza A viruses. , 2008, Organic & biomolecular chemistry.

[130]  T. Ashizawa,et al.  Induction of mammalian DNA topoisomerase I mediated DNA cleavage by antitumor indolocarbazole derivatives. , 1992, Biochemistry.

[131]  D. Melillo,et al.  Cyclization of unsaturated hydroxylamine derivatives , 1976 .

[132]  D. Knight,et al.  The reverse Cope cyclisation: a classical reaction goes backwards , 2004 .

[133]  David M Lemal,et al.  Perspective on fluorocarbon chemistry. , 2004, The Journal of organic chemistry.

[134]  K. Kaliappan,et al.  A tandem enyne/ring closing metathesis approach to 4-methylene-2-cyclohexenols: an efficient entry to otteliones and loloanolides. , 2012, Organic letters.