bluuebunny/crossref_metadata_2025 huggingface dataset:
Heteroaromatic Construction: The Li Synthesis of Mycoleptodiscin A
Authors: Taber Douglass F.
Published: November 2020

Kyungsoo Oh of Chung-Ang University cyclized (Org. Lett. 2015, 17, 450) the chloro enone 1 with NBS to the furan 2. Hongwei Zhou of Zhejiang University acylated (Adv. Synth. Catal. 2015, 357, 389) the imine 3, leading to the furan 4. H. Surya Prakash Rao of Pondicherry University found (Synlett 2014, 26, 1059) that under Blaise conditions, exposure of 5 to three equivalents of 6 led to the pyrrole 7. Yoshiaki Nishibayashi of the University of Tokyo and Yoshihiro Miyake, now at Nagoya University, prepared (Chem. Commun. 2014, 50, 8900) the pyrrole 10 by adding the silane 9 to the enone 8. Barry M. Trost of Stanford University developed (Org. Lett. 2015, 17, 1433) the phosphine-mediated cyclization of 11 to an intermediate that on brief exposure to a Pd catalyst was converted to the pyridine 12. Nagatoshi Nishiwaki of the Kochi University of Technology added (Chem. Lett. 2015, 44, 776) the dinitrolactam 14 to the enone 13 to give the pyridine 15. Metin Balci of the Middle East Technical University assembled (Org. Lett. 2015, 17, 964) the tricyclic pyridine 18 by adding propargyl amine 17 to the aldehyde 16. Chada Raji Reddy of the Indian Institute of Chemical Technology cyclized (Org. Lett. 2015, 17, 896) the azido enyne 19 to the pyridine 20 by simple exposure to I2. Björn C. G. Söderberg of West Virginia University used (J. Org. Chem. 2015, 80, 4783) a Pd catalyst to simultaneously reduce and cyclize 21 to the indole 22. Ranjan Jana of the Indian Institute of Chemical Biology effected (Org. Lett. 2015, 17, 672) sequential ortho C–H activation and cyclization, adding 23 to 24 to give the 2-substituted indole 25. In a complementary approach, Debabrata Maiti of the Indian Institute of Technology Bombay added (Chem. Eur. J. 2015, 21, 8723) 27 to 26 to give the 3-substituted indole 28. In a Type 8 construction, Nobutaka Fujii and Hiroaki Ohno of Kyoto University employed (Chem. Eur. J. 2015, 21, 1463) a gold catalyst to add 30 to 29, leading to 31.
Organocatalyzed C–C Ring Construction: The Carreira Synthesis of (+)-Crotogoudin
Authors: Taber Douglass F.
Published: November 2020

Kazuaki Kudo of the University of Tokyo developed (Org. Lett. 2013, 15, 4964) a peptide catalyst for the enantioselective construction of 3 by the addition of 2 to 1. Thorsten Bach of the Technische Universität München devised (Science 2013, 342, 840; J. Am. Chem. Soc. 2013, 135, 14948) a Lewis acid organocatalyst for the photo­cyclization of 4 to 5. Albert Moyano of the Universitat de Barcelona effected (Eur. J. Org. Chem. 2013, 3103) enantioselective conjugate addition of 7 to 6 to give the cyclopentane 8. Daniel Romo of Texas A&M optimized (Nature Chem. 2013, 5, 1049) the addition of 9 to 10 to give the β-lactone 11. Kamal Kumar and Herbert Waldmann of the Technische Universität Dortmund found (Angew. Chem. Int. Ed. 2013, 52, 9576) that the addition of 12 to 13 followed by Bayer–Villiger oxidation and deacylation delivered 14 in high ee. David W. Lupton of Monash University opened (Angew. Chem. Int. Ed. 2013, 52, 9149) the cyclopropane of 15 in situ, leading to an ester enolate that added to 16 to give 17. Jeffrey S. Johnson of the University of North Carolina used (Chem. Sci. 2013, 4, 2828) an organocatalyst to mediate the addition of the prochiral 18 to 19, leading to 20. M. Belén Cid of the Universidad Autónoma de Madrid added (J. Org. Chem. 2013, 78, 10737) the nitroalkane 22 to the unsaturated aldehyde 21, leading, after intramolecular Julia-Kocienski addition, to the cyclohexene 23. Additions that pro­ceed in high ee with cyclopentenone and cyclohexenone are often not as selective with cycloheptenone 24. Wei Wang of the University of New Mexico and Wenhu Duan of the Shanghai Institute of Materia Medica observed (Tetrahedron Lett. 2013, 54, 3791) that addition of nitromethane and of nitroethane to 24 were both highly effective. Strategies have been developed for applying organocatalysis to the assembly of polycarbacyclic ring systems. Sanzhong Luo of the Beijing National Laboratory for Molecule Sciences uncovered (Synthesis 2013, 45, 1939) a simple amine that effi­ciently catalyzed the Robinson annulation of 26 with 27 to give 28.
Organocatalyzed C–C Ring Construction: The Mihovilovic Synthesis of Piperenol B
Authors: Taber Douglass F.
Published: November 2020

M. Kevin Brown of Indiana University prepared (J. Am. Chem. Soc. 2015, 137, 3482) the cyclobutane 3 by the organocatalyzed addition of 2 to the alkene 1. Karl Anker Jørgensen of Aarhus University assembled (J. Am. Chem. Soc. 2015, 137, 1685) the complex cyclobutane 7 by the addition of 5 to the acceptor 4, followed by conden­sation with the phosphorane 6. Zhi Li of the National University of Singapore balanced (ACS Catal. 2015, 5, 51) three enzymes to effect enantioselective opening of the epoxide 8 followed by air oxidation to 9. Gang Zhao of the Shanghai Institute of Organic Chemistry and Zhong Li of the East China University of Science and Technology added (Org. Lett. 2015, 17, 688) 10 to 11 to give 12 in high ee. Akkattu T. Biju of the National Chemical Laboratory combined (Chem. Commun. 2015, 51, 9559) 13 with 14 to give the β-lactone 15. Paul Ha-Yeon Cheong of Oregon State University and Karl A. Scheidt of Northwestern University reported (Chem. Commun. 2015, 51, 2690) related results. Dieter Enders of RWTH Aachen University constructed (Chem. Eur. J. 2015, 21, 1004) the complex cyclopentane 20 by the controlled com­bination of 16, 17, and 18, followed by addition of the phosphorane 19. Derek R. Boyd and Paul J. Stevenson of Queen’s University Belfast showed (J. Org. Chem. 2015, 80, 3429) that the product from the microbial oxidation of 21 could be protected as the acetonide 22. Ignacio Carrera of the Universidad de la República described (Org. Lett. 2015, 17, 684) the related oxidation of benzyl azide (not illustrated). Manfred T. Reetz of the Max-Planck-Institut für Kohlenforschung and the Philipps-Universität Marburg found (Angew. Chem. Int. Ed. 2014, 53, 8659) that cytochrome P450 could oxidize the cyclohexane 23 to the cyclohexanol 24. F. Dean Toste of the University of California, Berkeley aminated (J. Am. Chem. Soc. 2015, 137, 3205) the ketone 25 with 26 to give 27. Benjamin List, also of the Max-Planck-Institut für Kohlenforschung, reported (Synlett 2015, 26, 1413) a parallel investigation. Philip Kraft of Givaudan Schweiz AG and Professor List added (Angew. Chem. Int. Ed. 2015, 54, 1960) 28 to 29 to give 30 in high ee.
Diels–Alder Cycloaddition: Pancratistatin (Cho), Nootkatone (Reddy), Platensimycin (Zhang/Lee), Scabronine G (Nakada), Isoglaziovianol (Trauner)
Authors: Taber Douglass F.
Published: November 2020

Samuel J. Danishefsky of Columbia University and the Memorial Sloan-Kettering Cancer Center made (Proc. Natl. Acad. Sci. 2013, 110, 10904) the unexpected obser­vation that methylation of the enolate derived from conjugate addition to the readily-prepared 1 followed by intramolecular alkene metathesis led to the trans fused ketone 2. This can be contrasted to the diastereo- and regioisomer 3, the product from Diels-Alder cycloaddition of 2-methylcyclohexenone to isoprene. The trans ring fusion of 2 is particularly significant because ozonolysis followed by aldol condensation would deliver the angularly-methylated trans-fused 6/5 C–D ring system of the steroids and related natural products. Cheon-Gyu Cho of Hanyang University added (Org. Lett. 2013, 15, 5806) the activated dienophile 4 to the dienyl lactone to give, after oxidation, the dibro­mide 5. Debromination followed by oxidation led to the antineoplastic lactam pancratistatin 6. D. Srinivasa Reddy of CSIR-National Chemical Laboratory Pune devised (J. Org. Chem. 2013, 78, 8149) a cascade protocol of Diels-Alder cycloaddition of 8 to the diene 7, followed by intramolecular aldol condensation, to give the enone 9. Oxidative manipulation followed by methylenation completed the synthesis of the commercially important grapefruit flavor nootkatone 10. Xinhao Zhang and Chi-Sing Lee of the Peking University Shenzen Graduate School uncovered (J. Org. Chem. 2013, 78, 7912) another cascade transformation, intermolecular addition of 11 to 12 followed by intramolecular Conia-ene cyclization, to give the tricyclic 13. Further manipulation led to an established intermediate for the total synthesis of platensimycin 14. Masahisa Nakada of Waseda University prepared (Angew. Chem. Int. Ed. 2013, 52, 7569) the enantiomerically-pure allene 15. Oxidation of the phenol to the monoketal of the cyclohexadienone set the stage for intramolecular cycloaddition to give 16. Oxidative cleavage followed by intramolecular alkene metathesis led to (+)-scabronine G 17. Dirk Trauner of the University of Munich assembled (Org. Lett. 2013, 15, 4324) the enantiomerically-pure alcohol 18. Oxidation gave the quinone, leading to intra­molecular Diels–Alder cycloaddition. The free alcohol then added to the exocyclic alkene of that product, to give, after further oxidation, the ether 19. Deprotection fol­lowed by reduction then completed the synthesis of (−)-isoglaziovianol 20.
Diels–Alder Cycloaddition: Fawcettimine (Zhai), Sculponeatin N (Zhai), Elansolid B1 (Kirschning), Frondosin A (Wright), Kingianin H (Parker), Rufescenolide (Snyder)
Authors: Taber Douglass F.
Published: November 2020

En route to fawcettimine 4, Hongbin Zhai of Lanzhou University found (Org. Lett. 2014, 16, 196) that microwave irradiation improved the efficiency of the cyclo­addition of the enone 1 with butadiene 2 to give 3. Takuya Kurahashi and Seijiro Matsubara of Kyoto University developed (Org. Lett. 2014, 16, 2594) a Ru complex that promoted the cycloaddition of butadiene with cyclic enones. In the course of a synthesis of sculponeatin N 7, Professor Zhai employed (Org. Lett. 2014, 16, 216) the silyl diene 5. After intramolecular cycloaddition, protonation of the resulting allyl silane with concomitant alkene migration led to the adduct 6. On the way to elansolid B1 10, Andreas Kirschning of Leibnitz Universität Hannover oxidized (Org. Lett. 2014, 16, 568) the alcohol 8 to the enone, that cyclized to 9. Under the influence of MgBr2, the cyclization proceeded with remarkable diastereocontrol. Dennis L. Wright of the University of Connecticut began (J. Am. Chem. Soc. 2014, 136, 4309) the synthesis of frondosin A 13 by preparing the secondary ether 11 in high ee. Diels–Alder cycloaddition of tetrabromocyclopropene gave, after exposure of the initial adduct to water, the dibromoenone 12. Kathlyn A. Parker of Stony Brook University explored (J. Org. Chem. 2014, 79, 919) the amine radical cation-promoted intermolecular Diels–Alder cycloaddition of the bicyclooctadiene 14. Three readily-separated diastereomeric dimers were observed. The diol 15, the precursor to kingianin H 16, was the major product. Scott A. Synder of Scripps/Florida described (J. Org. Chem. 2014, 79, 88) the interesting oxidative coupling of 17 with 18. The product 19 was readily carried on to rufescenolide 20.
The Nakada Synthesis of (+)-Ophiobolin A
Authors: Taber Douglass F.
Published: November 2020

Ophiobolin A 3 shows nanomolar toxicity toward a range of cancer cell lines. A central feature of this sesterterpene, isolated from the rice fungus Ophiobolus miyabeanus, is the highly-substituted eight-membered ring. A key step in the synthesis of 3 described (Chem. Eur. J. 2013, 19, 5476; Angew. Chem. Int. Ed. 2011, 50, 9452) by Masahisa Nakada of Waseda University was the acid-mediated cyclization of 1 to 2. The preparation of 1 began with the enantioselective hydrolysis of 4 to the mono­ester 5. Selective reduction followed by protection gave 6, that was carried on via 7 to 8. The ethoxyethyl group was selectively removed, and the alcohol was converted to an iodide (not illustrated) that was condensed with the lactone 9 to give 1. The cyclization of 1 could jeopardize the stereogenic center adjacent to the masked carbonyl, so eight diastereomers were possible. Careful optimization led to a prepar­atively useful yield of the desired product 2. Hydroboration gave 10, that was carried on to the aldehyde 11. The cyclopentanone 15 was prepared from the enantiomerically-enriched epox­ide 12. Opening with vinyl magnesium bromide followed by exposure to the second-generation Grubbs catalyst gave the diol 13, that was selectively protected, leading to 14. The derived bromohydrin was a mixture of regioisomers and diastereomers, from which, after oxidation, 15 dominated. Generation of the boron enolate from 15 in the presence of 11 gave the aldol product, that could be dehydrated with the Burgess rea­gent. Reduction with Raney nickel set the stereogenic center adjacent to the ketone, that was carried on to 16. Metathesis to close the eight-membered ring was not trivial. Finally, it was found that 17 could be induced to cyclize to 18 at an elevated temperature using the second-generation Hoyveda catalyst. Protecting group exchange gave 19. Routine functional group manipulation then completed the synthesis of (+)-ophiobolin 3. Some years ago, Neil E. Schore of the University of California, Davis showed (Tetrahedron Lett. 1994, 35, 1153) that the opening of Sharpless-derived epoxides such as 12 with vinyl nucleophiles was unexpectedly flexible. One set of conditions gave the expected inversion, but alternative conditions led to opening with clean retention (or double inversion) of absolute configuration.
The Njardarson Synthesis of Vinigrol
Authors: Taber Douglass F.
Published: November 2020

The diterpene vinigrol 3, isolated from Virgaria nigra F-5408, is a tumor necrosis factor (TNF) inhibitor. Jon T. Njardarson of the University of Arizona envisioned (Angew. Chem. Int. Ed. 2013, 52, 8648) that Wharton fragmentation of 1 could deliver 2, suit­ably functionalized for elaboration to 3. The tetracyclic 1 was prepared by the triply-convergent assembly of the phenol 11. Addition of allyl magnesium bromide to 4 proceeded with high regio- and geomet­ric selectivity, to give an alcohol that was methylated, then iodinated with inversion to give 5. Condensation of the phosphonate 7 with the derived aldehyde 6 led to the alcohol 8, that was coupled under Mitsunobu conditions with the phenol 9 to give 10. Oxidation of 11 gave an intermediate that underwent intramolecular Diels–Alder cycloaddition to deliver 12. On exposure to the Pd catalyst, 12 cyclized to the diene 13. On exposure to tBuOK/ tBuOH, the mesylate 1 smoothly fragmented to the hoped-for ketone 2. Although this has been referred to as a Grob fragmentation, in fact this reaction was developed (J. Org. Chem. 1961, 26, 4781) by Peter S. Wharton, then at the University of Wisconsin, and would more properly bear his name. Subsequent transformations took advantage of the hindered nature of the trisubsti­tuted alkene of 2. Hydrogenation of the disubstituted alkene proceeded selectively, to give an intermediate that was condensed with 14, leading to the enone 15. Two more selective hydrogenations, with the Wittig methylenation in between, completed the construction of the pendant isopropyl group. Once the isopropyl group was installed, what remained was the oxidation of 16 to 19. The epoxidation of 17 proceeded with high facial selectivity, to give an intermedi­ate that was carried on by iodination and reduction to the alcohol 18. Allylic oxidation converted 18 into 19, that was deprotected to give Vinigrol 3. It is instructive to compare and contrast this approach to vinigrol 3 with the two that we have previously highlighted (OHL September 6, 2010; December 24, 2012). Each strategy offers its own advantages.
The Kan Synthesis of the Streptomyces Alkaloid SB-203207
Authors: Taber Douglass F.
Published: November 2020

The alkaloid SB-203207 3, isolated from a Streptomyces species by a SmithKline Beecham group, was shown to inhibit isoleucyl tRNA synthetase with an IC50 of less than 2 nM. Toshiyuki Kan of the University of Shizuoka envisioned (Org. Lett. 2014, 16, 1646) that the carbocyclic core of 3 could be assembled by the Rh-mediated cycli­zation of 1 to 2. The authors had already demonstrated (Org. Lett. 2008, 10, 169) the cyclization of 1 to 2. For the assembly of 3, they needed to scale up the preparation of 1. To this end, they required the mandelamide 5 and the aldehyde 8. To prepare 5, they devised a new preparation of diazoacetates, condensation with bromoacetyl bromide followed by exposure to the bis sulfonamide. The aldehyde 8 was prepared from the acid 6 (commercial, or Org. Synth. 2004, Coll. Vol. 10, 228). The preparation of the third component of 3, the acid 9, had been described earlier by Banwell and Easton (Bioorg. Med. Chem. 2003, 11, 2687). The cyclization of 1 proceeded smoothly with 0.1% loading of the Rh catalyst, to give 2 in 72% de (85:15 ratio of enantiomers of the carbocyclic core). The enantio­meric excess could be upgraded by recrystallization of a later intermediate. The ester 2 was exchanged with allyl alcohol to give 10, presumably with recovery of the liberated chiral auxiliary 4. Formaldehyde added to the β-keto ester 10 from the more open face. Hydride addition from that same face then delivered the diol 11. The allyl ester was removed, and the free acid was activated with SOCl2 then condensed with ammonia to give the primary amide. Ozonolysis followed by acidic methanol led to cyclization onto the amide, allowing ready differentiation of the two ends of the alkene. Reduction com­pleted the preparation of the lactam 12. The nitrogen was sulfonylated, then the activated lactam was opened with assis­tance from the liberated primary alcohol. After acetal hydrolysis, the sulfonamide added to the aldehyde to give, after dehydration, the enamide 13. Inversion of the carboxyl converted the hydroxy acid to the urethane, that was formylated with the modified Vilsmeier reagent. Protection and deprotection followed by methylation then delivered the vinylogous amide 14.
The Lee Synthesis of (−)-Crinipellin A
Authors: Taber Douglass F.
Published: November 2020

The crinipellins are the only tetraquinane natural products. The enone crinipellins, including crinipellin A 3, have anticancer activity. Hee-Yoon Lee of the Korea Advanced Institute of Science and Technology (KAIST) envisioned (J. Am. Chem. Soc. 2014, 136, 10274) the assembly of 2 and thus 3 by the intramolecular dipolar cycloaddition of the diazoalkane derived from the tosylhydrazone 1. The initial cyclopentene was prepared from commercial 4 following the Williams procedure. Conjugate addition of the Grignard reagent 5 in the presence of TMS-Cl led to the silyl enol ether 6. Regeneration of the enolate followed by allylation gave 7. The preparation of the racemic ketone was completed by ozonolysis followed by selec­tive reduction and protection. Addition of hydride in an absolute sense led to separa­ble 1:1 mixture of diastereomers. Reoxidation of one of the diastereomers delivered enantiomerically enriched 8. A few steps later, after coupling with 10, the sidechain stereocenter was set by Sharpless asymmetric epoxidation. Oxidation of 11 gave the aldehyde, that was converted to the alkyne 12 by the Ohira protocol. Addition of the Grignard reagent 13 gave the allene 14 as an inconse­quential 1:1 mixture of diastereomers. Deprotection then led to the tosylhydrazone 1. The transformation of 1 to 2 proceeded by initial formation of the diazo alkane 15. Intramolecular dipolar cycloaddition gave 16, that lost N2 to give the trimethylene–methane diradical 17. The insertion into the distal alkene proceeded with remarkable stereocontrol, to give 2 as a single diastereomer—in 87% yield from 1. Direct α-hydroxylation of the ketone derived from 2 gave the wrong diastereo­mer, and hydride addition to 18 reduced the wrong ketone. As an alternative, the enantiomerically-pure sulfoximine anion was added to the more reactive ketone, and the product was reduced and protected to give 19. Allylic oxidation converted the alkene to the enone, and heating to reflux in toluene reversed the sulfoximine addi­tion, leading to 20. Epoxidation of 20 followed by α-methylenation delivered the enone 21, that proved to be particularly sensitive. Eventually, success was found with TASF. With a similarly sensitive substrate, Douglass F. Taber of the University of Delaware observed (J. Am. Chem. Soc. 1998, 120, 13285) that TBAF in THF buffered with solid NH4Cl worked well.
The Trauner Synthesis of (−)-Nitidasin
Authors: Taber Douglass F.
Published: November 2020

The sesterterpene (−)–nitidasin 4 is a component of the Peruvian infusion “hercam­puri,” prepared from the shrubs Gentianella nitida and Gentianella alborosea, that was used traditionally to treat hepatitis, diabetes, and hypertension. Dirk Trauner of Ludwig–Maximilians–Universität München envisioned (Angew. Chem. Int. Ed. 2014, 53, 8513) the assembly of 4 by the convergent coupling of 1 with 2 to give 3. For this strategy to be effective, both 1 and 2 had to be prepared in enantio­merically–enriched form. The skeleton of 1 was found in the enone 5, prepared by asymmetric Robinson annulation, that had already been carried on to the transfused ketone 6, and then to the enone 8 by way of 7. Following the authors earlier work (J. Org. Chem. 2012, 77, 5838), conjugate addition of 9 to the enone 8 gave 10. Hydrogenation of 10 had to be carried out with a Pt catalyst to avoid the unde­sired equilibration of the pendant group. Regioselectivity and diastereoselectivity in the hydroboration of the alkene 11 was optimized with the enantiomerically–pure borane. Allylation of the derived ketone was best effected by way of the enol borinate. Reduction of 12 with K–Selectride gave the cis alcohol, that was processed to the lac­tone. Kinetic alkylation then established the secondary methyl group. The lactone 13 was reduced to the diol, and protected as the bis TES ether. Selective oxidation of the primary TES ether generated the aldehyde, that could be methylenated without epimerization. Desilylation and oxidation then completed the synthesis of 1. The preparation of 2 began with commercial, enantiomerically–enriched citronel­lene 14. Oxidative cleavage of the more substituted alkene of 2 gave an aldehyde that was carried by the Corey–Fuchs protocol to the volatile enyne 15. This was cyclized with the Negishi reagent to an intermediate zirconacycle, that was oxidized to the diiodide. Elimination gave a diene, that was hydroborated with good kinetic control to give the alcohol 16. Oxidation followed by methylenation then completed the preparation of 2. The addition of an excess of the alkenyl lithium derived from 2, a 4:1 mixture of enantiomers, to the ketone 1 proceeded with remarkable diastereoselectivity.
Geochemical and Geophysical Constraints on Life’s Origin
Authors: Deamer David W.
Published: November 2020

Bernal's quote is a bit wordy, but he was basically saying that life can be understood as a continuous chemical reaction, and I agree. Throughout this book I will be describing ideas about how life can begin on habitable planets, which are defined as planets with orbits not too close and not too far from a star so that the temperature permits liquid water to exist. The conditions in which life can begin must have sufficient complexity to permit primitive life to assemble from organic chemicals dispersed in a sterile environment which then begin to react and evolve into more complex structures. This chapter will describe the main parameters of geochemical and geophysical complexity, and then consider them in terms of scales from the nanoscopic to the macroscopic. Questions to be addressed: What scales must be considered to understand how life can begin? What are the properties of the scales? How do the scales relate to the origin of life? The physical dimensions related to the origin of life can be described in terms of four scales—global, local, microscopic, and nanoscopic— and these dimensions must be related to the chemical and physical properties of each scale. The global scale is easiest to understand because the parameters are averages of very broad variables. For instance, we can state that the global temperature today is 15° C and even follow changes in the temperature to accuracies of a tenth of a degree on a year to year basis. However, within the global scale are extreme variations between winter temperatures of - 60° C at the poles and summer temperatures of 50° C in Death Valley, California. Of course, even higher temperatures are associated with hydrothermal fields, up to boiling at 100° C, but sometimes nearer to 90° C because the fields are usually at higher elevations associated with volcanoes. Table 2.1 summarizes the main parameters of the global scale on Earth and Mars today and compares their values with those near the time that life began on the Earth 4 billion years ago.
Testing Alternative Hypotheses
Authors: Deamer David W.
Published: November 2020

Narratives related to the origin of life all incorporate the assumption that the first living microorganisms emerged in a sterile planetary surface after the ocean condensed over 4 billion years ago. This means that even though global conditions can be deduced from our growing understanding of planetary science and the early solar system, laboratory simulations of localized prebiotic sites remain the only way to guide virtually all of the attempts to reproduce the chemical and physical processes by which life could emerge. Because simulations are used to test the hypotheses described in this book, it seems essential to review representative examples and consider their strengths and limitations. Laboratory simulations of the prebiotic environment incorporate specific sets of factors chosen to reflect what we can deduce about the atmosphere, lithosphere, and hydrosphere of the early Earth and Mars. This chapter attempts to sort out the main factors that are incorporated into simulations. These can be conveniently divided into the drivers—physical and chemical processes—and the emergent complexity that is a product of the drivers. In order to describe a given system, it is helpful to first provide abbreviations for the component factors that define the degree of complexity, then compare that complexity to the complexity that seems to be required for life to begin, as is done in the next section. Questions to be addressed: What factors and assumptions provide a foundation for a given simulation? How do the factors interact to produce increasing complexity? How can the factors guide the design of experimental approaches? What combination of factors would be an adequate simulation of the prebiotic condition? Laboratory investigations related to origin of life research often begin with mixtures of simple organic molecules assumed to be available on the prebiotic Earth. These are then allowed to undergo reactions driven by a source of energy, either impinging on the system such as ultraviolet light or electrical discharge or contained within chemically activated compounds that can undergo spontaneous reactions. The mixture typically becomes more complex in some interesting way, such as the synthesis of polymers described in earlier chapters.
Integrating Chemistry, Geology, and Life’s Origin Coauthored with Bruce Damer
Authors: Deamer David W.
Published: November 2020

Chapter 8 recalled John Platt’s recommendation that testing alternative hypotheses is a preferred way to perform research rather than focusing on a single hypothesis. Karl Popper proposed an additional way to evaluate research approaches, which is that a strong hypothesis is one that can be falsified by one or more crucial experiments. This chapter proposes that life can begin with chance ensembles of encapsulated polymers, some of which happen to store genetic information in the linear sequences of their monomers while others catalyze polymerization reactions. These interact in cycles in which genetic polymers guide the synthesis of catalytic polymers, which in turn catalyze the synthesis of the genetic polymers. At first, the cycle occurs in the absence of metabolism, driven solely by the existing chemical energy available in the environment. At a later stage, other polymers incorporated in the encapsulated systems begin to function as catalysts of primitive metabolic reactions described in Chapter 7. The emergence of protocells with metabolic processes that support polymerization of self-reproducing systems of interacting catalytic and genetic polymers marks the final step in the origin of life. The above scenario can be turned into a hypothesis if it can be experimentally tested— or falsified, as described in the epigraph. The goal of falsification tends to be uncomfortable for active researchers. It’s a very human tendency to be delighted with a creative new idea and want to prove it correct. This can be such a strong emotion that some fall in love with their idea and actually hesitate to test it. They begin to dislike colleagues who are critical and skeptical. However, my experience after 50 years of active research is that we need to think of our ideas as mental maps and expect that most of them will not match the real world very well. And so, I say to my students, “When you have a new idea it’s OK to enjoy it and share it with others, but then you must come up with an experiment that lets you discard it.
Neill’s Dilemma
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

“Dad, you cannot be serious!” Julie had made what she thought was a simple request: Could she go to the hockey game with her friends on Friday night? To her father, Neill, it was a very big deal. That Friday would be the first anniversary of the death of his wife (Julie’s mother), Deanna. Neill had spent weeks figuring out just the right way to mark the date, ultimately deciding to take his four children to visit the gravesite, release balloons, and then have dinner at what had been Deanna’s favorite restaurant. Most importantly, they would spend the day together as a family, something Deanna would have liked. Now, with the anniversary only a week away, his fifteen-year-old daughter wanted out. “Are you really saying that I can’t go?” Julie asked again. “That’s exactly what I’m saying,” Neill said tersely. “You do realize why next Friday is so important, right?” When he questioned whether she cared more about going to a hockey game than honoring her mother, Julie became indignant. She shot back that just because she wanted to hang out with her friends did not mean she had forgotten about Mom. The argument escalated quickly. Neill was resolute; like it or not, she would be spending next Friday night with her family. Julie stormed off to her room and slammed the door. For the next several days, they barely spoke to each other. Neill could not believe his daughter was acting as if the first anniversary of her mother’s death was just another day. Still, he hated that they were arguing. He knew that Julie was grieving too and he worried, not for the first time since Deanna died, that his initial reaction had been unnecessarily harsh. Neill felt lost and alone. As he had done from time to time over the past year, he lay down on his bed, looked up, and talked aloud to Deanna. But the one-way “conversation” brought little clarity. The next night, Neill attended a support group for men who were widowed fathers raising children on their own.
Beyond Death and Dying
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

In the late 1960s, LIFE magazine was one of the most widely read and influential periodicals in the world. Renowned for its photojournalism, the general-interest magazine covered all aspects of American life. The November 21, 1969, edition was no exception. It included a review of what would be The Beatles’ final studio album, a profile of Ohio State University head football coach Woody Hayes, and an advertisement for a commemorative book on that summer’s moon landing. It also featured an article on a little-known University of Chicago psychiatrist, Dr. Elisabeth Kübler-Ross, and her groundbreaking work with terminally ill patients. In an era when public discourse about death and dying was almost non-existent and when many physicians believed that a patient was better off not knowing his or her prognosis, Kübler-Ross was encouraging candid and open conversations with people about their impending deaths. Her innovative approach and courage to challenge the status quo drew the interest of LIFE editor Loudon Wainwright. His captivating story introducing Kübler-Ross and her new book, On Death and Dying, would forever change the national conversation about end-of-life and grief. The article described Kübler-Ross’s seminar teaching clinicians about the experiences of terminally ill patients. Physicians, nurses, chaplains, and medical students watched through a one-way mirror as she interviewed a twenty-two-year-old woman who had been diagnosed just two weeks earlier with leukemia, which at that time was almost always fatal. Large black-and-white pictures of the patient showed a vibrant and beautiful young woman with long hair and a wide smile. She looked nothing like someone close to death, which in some ways was the point. She talked about her diagnosis and understanding that leukemia would almost certainly kill her. Her willingness to openly discuss the prospect of her own death must have been astounding to those observing the interview. Kübler-Ross theorized that people facing their own mortality proceed through five stages prior to their death. In the first stage, the person is unable or unwilling to accept that he or she is going to die (Denial).
Band of Brothers
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

The group dynamic had changed over the first six months. The fathers’ initial apprehension had been replaced by a shared understanding of their work together. During the first several meetings, we had been more active in leading the discussion. Increasingly, the men took ownership of each session. They set the agenda and wasted little time getting down to business. Perhaps most importantly, they felt part of something special and clearly began to care about each other. We noticed that when the fathers arrived for group meetings, they were more likely to give each other a hug than the formal handshakes that had marked the early months. Similarly, the men would often remain talking with each other in the parking lot well after the sessions ended. Prior to the seventh meeting, two fathers who had recently lost their wives and had heard about our program contacted us about joining the group. We asked the five current members whether they were open to including new fathers. Not surprisingly, they were unanimous and enthusiastic about the idea. The following month, Russ and Steve attended their first meeting. Russ is a former Marine and a man of few words. When he does speak, he is direct and straight to the point. After introducing himself, Russ described the day less than a year earlier when his own nightmare began. He was in New York City for business when a neighbor called to tell him that his wife, Kelley, had been taken to the hospital with sudden abdominal pain. Russ caught the first flight out of LaGuardia and was waiting for her by the time she got out of emergency surgery to remove her gall bladder. Over the next several days, Kelley recovered and the worst seemed to be behind her. Then the pathology report came back positive for gall bladder cancer. Her doctor mentioned the possibility of a lab error, since this diagnosis is so rare in women Kelley’s age. He wanted to re- run the tests and meet the following week to discuss the results.
The Good Enough Father
Authors: Rosenstein Donald L. , Yopp Justin M.
Published: November 2020

Donald Winnicott served in World War I and graduated from medical school before he reached the age of twenty-four. He accepted a position at London’s Paddington Green Children’s Hospital where he would work as a pediatrician for the next four decades. Early in his career, he became fascinated with theories of emotional development in infants and young children and subsequently trained to be a psychoanalyst. After observing thousands of interactions between young children and their mothers, Winnicott became convinced that the best way for parents to promote their children’s psychological health was to help them navigate interpersonal relationships. Ultimately, he became one of the most influential psychoanalysts of the twentieth century. Perhaps Winnicott’s most enduring insight is the notion of the “good enough mother.” His fundamental precept was that perfect parenting is neither possible nor desirable and that children benefit most when their caregivers do not immediately respond to each and every demand. He maintained that this approach teaches children to tolerate frustration and disappointment. Additionally, when children are allowed to fail in small and manageable ways, they learn to self-soothe and develop the competence to negotiate an imperfect world. Thus, the “good enough” parent is preferable to the “perfect” parent who aims (and inevitably fails) to meet his or her child’s every desire. Recognizing that most caregivers possess the necessary instincts and interpersonal resources to care for their children, Winnicott championed the notion of the “good enough mother” to promote more realistic parental expectations and remind caregivers that children can thrive with loving, competent but “imperfect” parents. This simple but profound idea would prove extremely valuable to the fathers in our group. In Part II, we address four broad challenges that the seven men faced: assuming sole responsibility for all parenting and household duties; helping their children grieve the loss of their mothers; coping with their own grief; and taking steps to move forward with their lives. Every one of them found that the most pressing initial tasks were adapting to sole parenting and managing the home.
The Periodic Table Retrieved from Density Functional Theory Based Concepts: The Electron Density, the Shape Function and the Linear Response Function
Authors: Geerlings Paul
Published: November 2020

“The periodic table of the elements is one of the most powerful icons in science: a single document that captures the essence of chemistry in an elegant pattern.” This statement taken from Eric Scerri’s marvelous book The Periodic Table: Its Story and Its Significance (Scerri 2007) grasps in one simple sentence the status that the periodic table has acquired in chemistry, but not only in chemistry: every person all over the world who took high school chemistry remembers for the rest of his/her life at least one thing from it (and from science courses in general): this mysterious table of the elements omnipresent in all books and documents, often decorating the classroom. Why? Although the answer is not easy it is probably because a whole discipline of science is condensed in a simple table or scheme offering at one glimpse the essence (and the beauty) of a part of science which for the rest of the lives of many students will remain unexplored—and even for which these students will create an aversion among others in view of the “polluting role” of chemistry. Nevertheless at some moment in their lives these students felt “something” that was remarkable and which they always remember, as witnessed by their comments when visiting their old school of university with their children. In the hierarchy of the sciences chemistry is often considered, mainly by physicists, as the “physics of the outer shell.” It is sometimes said that chemistry, as also quoted by Scerri (2007), has no deep ideas, not a few fundamental laws like in physics or biology (such as those governing quantum mechanics, relativity and evolution), but the not-so-distant observer will disagree: chemical periodicity as precisely reflected in the periodic table is in my view not only the most fundamental law of chemistry, but is a law or if you want an “organizing principle” with the same status as these famous laws in adjacent disciplines! Chemical periodicity is at the heart of reducing an astonishing amount of experimental data (and nowadays theoretical data as well) to a limited number of patterns often with common origin, enabling one to understand and interpret the properties of the now more-than 50 million compounds registered in the databases of the Chemical Abstracts Services (Toussant, 2009).
The Origin of Mendeleev’s Discovery of the Periodic System
Authors: Kaji Masanori
Published: November 2020

D.I. Mendeleev (1834–1907) was a 19th-century Russian chemist whose discovery of the periodic law is a milestone of 19th century chemistry and continues to occupy a central place in chemistry. Despite an enormous amount of study on the origin of Mendeleev’s discovery of the periodic law, relatively little research has been done on either the conceptual or social origin of the law. This chapter aims to fill that gap. B. M. Kedrov (1903–1985) was a pioneering historian on the origin of Mendeleev’s discovery. Kedrov discovered Mendeleev’s archived materials related to his first periodic table (dated February 17, 1869) at the Mendeleev Museum in the St. Petersburg State Museum at the end of the 1940s. He then began full-fledged research on Mendeleev’s discovery of the periodic law, which culminated in the publication of The Day of a Great Discovery (Kedrov 1958) and other books which are generally reliable resources (Mendeleev and Kedrov 1958, 1960). In his meticulous reconstruction of Mendeleev’s compilation of the first periodic table, Kedrov emphasized the “one-day discovery” (February 17, 1869), and paid only scant attention to both Mendeleev’s earlier works and the social context of the discovery. At about the same time, R. B. Dobrotin analyzed Mendeleev’s earliest works, especially those of the 1850s, and argued that essential elements of the future periodic system already existed (Dobrotin 1953; Shchukarev and Dobrotin 1954). However, Kedrov’s version of the discovery had a dominant influence on Soviet history of science. In the 1970s, A. A. Makarenya cautiously expressed some doubts about Kedrov’s description of Mendeleev’s scientific works (Makarenya 1972). After Kedrov’s death, D. N. Trifonov proposed in 1990 “Version-2” of the discovery and criticized Kedrov’s “one-day version” (Trifonov 1990). Starting from a critical reevaluation of Kedrov’s research, very different reconstructions have recently been proposed. These reconstructions pay more attention to Mendeleev’s earlier works and incorporate a broader historical context.
“The Most Terrible Jaws Afloat”
Authors: Colby Jason M.
Published: November 2020

Gaius plinius secundus had witnessed a lot of violence in his life—war in Germania, Sicilian raids, Nero’s reign of terror—but killer whales really seemed to scare him. Known to history as Pliny the Elder, he penned the first known description of Orcinus orca in his encyclopedic Naturalis Historia, completed shortly before his death in 79 CE. It painted a bloody picture. The orca “cannot be in any way adequately described,” Pliny asserted, “but as an enormous mass of flesh armed with teeth.” Whereas dolphins sometimes befriended people and even helped fishermen, the killer whale preyed on mother baleen whales and their vulnerable calves. “This animal attacks the balaena in its places of retirement,” he wrote, “and with its teeth tears its young, or else attacks the females which have just brought forth, and, indeed, while they are still pregnant.” Fleeing whales could expect no mercy from orcas, who “kill them either cooped up in a narrow passage, or else drive them on a shoal, or dash them to pieces against the rocks.” So frightful were these battles to behold, Pliny noted, that it appeared “as though the sea were infuriate against itself.” In short, the destructive power of a killer whale had to be seen to be believed. Pliny himself had seen one. Around 50 CE, an orca had wandered into the harbor of Ostia, Rome’s port city. The animal had been drawn there, it seemed, by a ship from Gaul, which had run aground and spilled its cargo of hides. As the whale investigated, it became stuck in the shallows, unable to maneuver. Soon its back and dorsal fin were visible above the water, recounted Pliny, “very much resembling in appearance the keel of a vessel turned bottom upwards.” Sensing an opportunity, the emperor Claudius arrived from Rome, ordering local fishermen to net off the harbor. After waiting for a crowd to gather, he led his praetorians into battle against the trapped whale. The result was “a spectacle to the Roman people,” wrote Pliny. “Boats assailed the monster, while the soldiers on board showered lances upon it.” But the orca fought back, sinking at least one vessel before it succumbed.
Skana and the Hippie
Authors: Colby Jason M.
Published: November 2020

On september 21, 1967, Vancouver columnist Himie Koshevoy of the Province newspaper witnessed an unexpected Cold War encounter. Soviet minister of fisheries Alexander Ishkov had come to see the Vancouver Aquarium, and Murray Newman invited the reporter along. Ishkov had visited in 1956, when construction of the aquarium was still underway, and he was so impressed that he carried a copy of its plans back to Moscow. Eleven years later, he had returned for a grand tour, and Newman was happy to oblige. He showed his Soviet guest around the exhibits, proudly noting that each year forty thousand schoolchildren visited the aquarium, “gaining knowledge of their coastal environment.” Like most visitors that year, Ishkov was especially eager to see Skana, Vancouver’s captive killer whale. According to Koshevoy, what ensued between communist fishing minister and US-caught orca amounted to “a Little Yalta.” With “squeals of delight,” Skana showed off her acrobatic feats, earning a handful of herring for each one. Although Ishkov may not have grasped the significance of Skana “profiting through her labors,” Koshevoy quipped, the Soviet official clearly enjoyed the performance. When his hosts suggested Ishkov try feeding Skana himself, however, he hesitated. “You could almost see the thoughts racing,” mused Koshevoy. “Was she a potential aggressor? Could he deter an attack? The first-strike ability was clearly on the whale’s side.” Finally, coaxed by trainer Terry McLeod, Ishkov made his démarche, and Skana accepted. As Ishkov smiled and rubbed the whale’s head, it was clear the crisis had passed. The interspecies summit closed, Koshevoy noted, with “mutual expressions of goodwill on all sides.” It was a waggish depiction of the visit, to be sure. Although the Soviet official didn’t want to look skittish in front of his North American hosts, the Cold War was likely far from his mind as he dropped herring into Skana’s maw. Ishkov shared Newman’s interest in fish and marine mammals, and he had recently outlawed the killing of small cetaceans in Soviet waters. Yet he was undeniably part of the political world, and he represented a Soviet empire that was asserting its interests around the globe.