Albert Eschenmoser
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 B. 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. Early work and Vitamin B 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. 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. TNA and Artificial Nucleic Acids. Eschenmoser developed synthetic pathways for artificial nucleic acids, specifically modifying the sugar backbone of the polymer. 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.