Albert Jakob Eschenmoser (born 5 August 1925) is a Swiss organic chemist best known for his

work on the synthesis of complex heterocyclic natural compounds, most notably vitamin B12. In
addition to his significant contributions to the field of organic synthesis, Eschenmoser pioneered
work in the Origins of Life (OoL) field with work on the synthetic pathways of artificial nucleic
acids. Before retiring in 2009, Eschenmoser held tenured teaching positions at the ETH Zurich
and The Skaggs Institute for Chemical Biology at The Scripps Research Institute in La Jolla,
California as well as visiting professorships at the University of Chicago, Cambridge University,
and Harvard.

Contents
 1 Early work and Vitamin B12 Synthesis
 2 Origins of Life (OoL) Research
 3 TNA and Artificial Nucleic Acids
 4 Awards
 5 References
 6 External links

Early work and Vitamin B12 Synthesis

Eschenmoser began his scientific career as a graduate student in the laboratory of Leopold
Ružička, at the Eidgenossische Technische Hochschule (ETH) in Zurich. Ruzicka was a notable
organic chemist himself having been awarded the Nobel Prize in Chemistry in 1939 for his work
on the synthesis of androsterone and testosterone. Eschenmoser’s early work on the cyclization
of unsaturated, conjugated hydrocarbons directly contributed to advances in the field of terpene
chemistry and provided insight into steroid biosynthesis.[1][2]

A/D-corrin-ring closure by photochemical A/D-seco-corrin→corrin cycloisomerization, key step

in the ETH Zurich A/D variant of the total synthesis of vitamin B12
In the early 1960s, having become Professor of General Organic Chemistry at ETH,
Eschenmoser began work on what was the most complex natural product synthesized at the time
—vitamin B12. In a remarkable collaboration with his colleague Robert Burns Woodward at Harvard
University, a team of almost one hundred students and postdoctoral workers worked for many
years on the total synthesis of this molecule. At the time, a significant obstacle to the synthesis of
vitamin B12 had been the difficulty in the final macrocyclic ring closure necessary to complete
the corrin ring structure at the center of the molecule.[3] Eschenmoser and his collaborators
discovered methods under which such bonds between corrin ring building blocks could be
formed, including a novel photochemical process which established the final junction of rings A
and D with a high degree of stereospecificity, the key step in what was dubbed the “A/D variant”
of the syntheses.[4] Both the Harvard/ETH “A/B variant” and the ETH “A/D variant” of the
syntheses were jointly and concomitantly completed in 1972, and they marked a landmark in the
history of organic chemistry.

The Eschenmoser fragmentation, the Eschenmoser sulfide contraction and Eschenmoser's salt are
named after him.

Origins of Life (OoL) Research

A particularly vexing question in the study of the chemical origins of life is the selection of
ribose, which forms the backbone of the nucleic acids found in modern biological systems.
Eschenmoser’s work on a variant of the formose reaction that produces phosphorylated ribose in
relatively significant concentrations has provided significant insight. Eschenmoser and
colleagues demonstrated that phosphorylated glycoaldehyde when condensed with
glyceraldehyde (a product of successive formaldehyde condensations) produces phosphorylated
ribose differentially, providing a plausible explanation for the origin of both the sugar ribose, and
the phosphate group required to polymerize monomeric nucleotides, in modern biochemistry.[5]

TNA and Artificial Nucleic Acids

Eschenmoser developed synthetic pathways for artificial nucleic acids, specifically modifying
the sugar backbone of the polymer.[6] Having developed a number of structural alternatives to the
naturally occurring nucleic acids, Eschenmoser and his colleagues were able to contrast the
properties of these synthetic nucleic acids with naturally occurring ones to effectively determine
the properties of RNA and DNA vital to modern biochemical processes. This work demonstrated
that hydrogen-bonding interactions between the base-paring surfaces of the nucleobases alone
might not have provided sufficient selection pressure to lead to the eventual rise of ribose in the
structure of modern nucleic acids. He determined that pentose sugars, particularly ribose,
conform to a geometry that contributes significantly to the helical structure of DNA by
optimizing base-pair stacking distances in naturally occurring oligonucleotides. These base-
stacking interactions orient and stabilize the base-paring surfaces of the nucleobases (A, G, C, T
or U in RNA) and give rise to the canonical Watson-Crick base-paring rules that are well
understood today.
Threose nucleic acid is an artificial genetic polymer invented by Eschenmoser. TNA strings
composed of repeating threose sugars linked together by phosphodiester bonds. Like DNA and
RNA, the molecule TNA can store genetic information in strings of nucleotide sequences. John
Chaput, a professor at UC Irvine, has theorized that issues concerning the prebiotic synthesis of
ribose sugars and the non-enzymatic replication of RNA may provide circumstantial evidence of
an earlier genetic system more readily produced under primitive earth conditions. TNA could
have been an early pre-DNA genetic system.[7]

Awards
 Kern Prize of the ETH Zurich (1949)
 Werner Prize of the Swiss Chemical Society (1956)
 Ruzicka Prize of the ETH Zurich (1958)
 Ernest Guenther Award (1966)
 Austrian Cross of Honour for Science and Art (1974)
 Welch Award (1974)
 Davy Medal (1978)
 Tetrahedron Prize for Creativity in Organic Chemistry (1981)
 Arthur C. Cope Award (1984)
 Wolf Prize of the Wolf Foundation, Tel Aviv, Israel (1986)
 Nakanishi Prize (1998)
 Oparin Medal (2002)
 Frank H. Westheimer Medal (Harvard University (2004)
 F.A. Cotton Medal for Excellence in Chemical Research of the American Chemical
Society
 Paul Karrer Gold Medal (University of Zurich, 2008)
 Benjamin Franklin Medal in Chemistry from the Franklin Institute in Philadelphia,
Pennsylvania (2008)
 Honorary doctorates (Dr. hc) from the University of Fribourg (Switzerland, 1966),
University of Chicago (USA, 1966), University of Edinburgh (United Kingdom, 1979),
University of Bologna (Italy, 1989), Johann Wolfgang Goethe University (Frankfurt am
Main, 1990), Louis Pasteur University (France, 1991), Harvard University (USA, 1993),
Scripps Research Institute (USA, 2000) and the University of Innsbruck (Austria, 2010).

References
1.

 Eschenmoser, Albert (1955). "Eine Stereochemische Interpretation der biogenetischen

Isoprenregel bei den Triterpenen" (PDF). Helvetica Chimica Acta. 38: 1890.
doi:10.1002/hlca.19550380728.
  Eschenmoser, Albert (2007). "The Search for the Chemistry of Life's Origin".
Tetrahedron. 63 (52): 12821–12844. doi:10.1016/j.tet.2007.10.012.
  For the seminal work at ETH on synthetic approaches to the corrin ring system which
preceeded and accompanied the work on the vitamin B12 syntheses, see Eschenmoser, Albert
(2015). "Introductory Remarks on the Publication Series 'Corrin Syntheses-Parts I-VI'".
Helvetica Chimica Acta. 98 (11–12): 1475–1482. doi:10.1002/hlca.201400399. Eschenmoser,
Albert (2015). "Corrin Syntheses. Part I". Helvetica Chimica Acta. 98 (11–12): 1483–1600.
doi:10.1002/hlca.201400277. Scheffold, Rolf; Bertele, Erhard; Gschwend, Heinz; Häusermann,
Werner; Wehrli, Pius; Huber, Willi; Eschenmoser, Albert (2015). "Corrin Syntheses. Part II".
Helvetica Chimica Acta. 98 (11–12): 1601–1682. doi:10.1002/hlca.201200095. Pesaro, Mario;
Elsinger, Fritz; Boos, Helmut; Felner-Caboga, Ivo; Gribi, Hanspeter; Wick, Alexander;
Gschwend, Heinz; Eschenmoser, Albert (2015). "Corrin Syntheses. Part III". Helvetica Chimica
Acta. 98 (11–12): 1683–1754. doi:10.1002/hlca.201200308. Bertele, Erhard; Scheffold, Rolf;
Gschwend, Heinz; Pesaro, Mario; Fischli, Albert; Roth, Martin; Schossig, Jürgen;
Eschenmoser, Albert (2015). "Corrin Syntheses. Part IV". Helvetica Chimica Acta. 98 (11–12):
1755–1844. doi:10.1002/hlca.201200342. Blaser, Hans-Ulrich; Winnacker, Ernst-Ludwig;
Fischli, Albert; Hardegger, Bruno; Bormann, Dieter; Hashimoto, Naoto; Schossig, Jürgen;
Keese, Reinhart; Eschenmoser, Albert (2015). "Corrin Syntheses. Part V". Helvetica Chimica
Acta. 98 (11–12): 1845–1920. doi:10.1002/hlca.201300064. Yamada, Yasuji; Wehrli, Pius;
Miljkovic, Dusan; Wild, Hans-Jakob; Bühler, Niklaus; Götschi, Erwin; Golding, Bernard;
Löliger, Peter; Gleason, John; Pace, Brian; Ellis, Larry; Hunkeler, Walter; Schneider, Peter;
Fuhrer, Walter; Nordmann, René; Srinivasachar, Kasturi; Keese, Reinhart; Müller, Klaus;
Neier, Reinhard; Eschenmoser, Albert (2015). "Corrin Syntheses. Part VI". Helvetica Chimica
Acta. 98 (11–12): 1921–2054. doi:10.1002/hlca.201500012.
  Eschenmoser, A. (1971). Studies on Organic Synthesis. XXIIIrd International Congress
of Pure and Applied Chemistry: special lectures presented at Boston, USA, 26-30 July 1971. 2.
London: Butterworths. pp. 69–106. doi:10.3929/ethz-a-010165162. hdl:20.500.11850/84699.
ISBN 0-408-70316-4. Eschenmoser, A.; Wintner, C. (1977). "Natural product synthesis and
vitamin B12". Science. 196 (4297): 1410–1420. Bibcode:1977Sci...196.1410E.
doi:10.1126/science.867037. PMID  867037.
  Muller (1990). "Synthesis of IH-Cyclopropal[g]quinoline via Trapping of an ortho-
Quinodimethane". Helvetica Chimica Acta. 73: 1410–1468. doi:10.1002/hlca.19900730526.
  Eschenmoser, Albert (1988). "Vitamin B12: Experiments Concerning the Origin of Its
Molecular Structure". Angew. Chem. Int. Ed. 27: 5–39. doi:10.1002/anie.198800051.
 Harth, Richard (January 8, 2012). "Simpler times: Did an earlier genetic molecule predate
DNA and RNA?". Retrieved 11 November 2016.