Frieder Wilhelm Lichtenthaler

Frieder Lichtenthaler was born in Heidelberg, Germany, on 19. January 1932 as the oldest of five sons of Wilhelm, a schoolteacher, and his wife Emma.

During his secondary school days in the countryside around Heidelberg, a fondness for chemistry emerged, mostly due to the influence of an inspirational teacher who happened to have a Ph.D. with Karl Freudenberg, a leading carbohydrate chemist of his time.

After graduation in 1951, he had to wait for some time before being admitted to university, as many German universities were in the phase of reconstruction from the damages of the war. During this time, Lichtenthaler could work as a lab helper in the personal laboratory of Prof.   Freudenberg in Heidelberg.

In 1952, he was admitted to study chemistry, gaining his "Vordiplom" in 1954 and "Diplom" in 1957 with a study on the Pinner reaction in the group of Prof. Friedrich Cramer. In the same group he carried out research on enol phosphates for his Ph.D. in 1959.

Lichtenthaler then joined the laboratory of Hermann O. L. Fischer, son of Emil Fischer (Nobel laureate 1902), at the University of California, Berkeley, USA, where he participated in the further exploitation of the nitromethane cyclisation of dialdehydes.   Applied to glyoxal, a stunning fourfold addition led to a mixture of 1,4-dinitro-inositols from which the neo-1,4-isomere crystallized. Its configuration was established by 1H-NMR, which, in 1960, was one of its very early straightforward applications. The spectra were run at the research facilities of Varian in Palo Alto, CA, on an experimental 30 MHz machine.

Following this reaction principle, Lichtenthaler established a simple way to synthesize amino sugars, which were important synthetic targets at the time due to their occurrence in amino glycoside antibiotics. 

Undoubtedly even more would have been forthcoming had it not been for the premature death of H.O.L.Fischer in 1960. This untimely event, however, set Lichtenthaler's focus on the history of organic chemistry. H.O.L.Fischer, when he left Germany in 1932, took with him the personal library of his father all the way to Berkeley and Mrs. Fischer asked Lichtenthaler to go through all the books, manuscripts, photographs and the entire correspondence of Emil Fischer to establish their content. Later these "Emil Fischer Papers" were donated to the Bancroft Library at UC Berkeley where they are available upon request. This early initiation into the history of chemistry and into that of carbohydrate chemistry in particular, found its expression over many years in various historical essays by Lichtenthaler.

In 1961, he returned to Germany and joined the chemistry faculty of the Technical University of Darmstadt, headed by Prof. Clemens Schoepf and aquired his habilitation in 1963. He was appointed Associate Professor in 1968 and Full Professor in 1972, a position he retained until retirement in 2000, despite attractive offers from the universities of Hohenheim and Kiel. He served the faculty of chemistry as dean in 1977-1979, and played an active role in the construction of the new chemistry building at the new campus of the university.

His research, spanning over 50 active years, has resulted in over 300 publications which may be summarized under the header "carbohydrate chemistry".

Based on the nitroalkane-condensation, Lichtenthaler expanded his work on purine   and pyrimidine nucleosides carrying one or more amino function in the carbohydrate part. Following the reaction sequence: periodate cleavage, nitromethane condensation, and catalytic hydrogenation, a number of amino nucleosides were made accessible. The configuration on 2`-, 3`-, and 4`-position were analysed by NMR spectroscopy, which was just being established at German universities. This methodology was used in different total syntheses of nucleoside antibiotics and dipeptyl-amino sugar nucleosides like gougerotine. During these synthetic activities, a general and simple method could be established for the selective glycosidation of purines at the 9-position. This early work still plays an important role in certain industrial processes for the production of nucleosides today. Especially in the synthesis of allopurinol ribosides this process proves more effective than the classical Hilbert-Johnson method.

Parallel to his work on nucleosides, Lichtenthaler already started in the 1960s to transform monosaccharides, which naturally occur in large amounts, into chiral building blocks. Many different methods were developed in his group to transform the sugars, which were overfunctionalised with hydroxyl groups of similar reactivity into simple chiral building blocks containing useful functional groups like C-C- and C-O-double bonds. Besides the normal carbonyl-reactivity, the selective oxidation of one hydroxyl group, generated a gradated C-H-acidity depending on the substitution pattern. By a controlled elimination reaction, "sugar-enolones" were created, which were easily accessible and very useful chiral building blocks. Depending on the order of the chemical steps, the carbonyl function could be introduced in 2- (2-ulose), 3- (3-ulose), or in 4- (4-ulose) position. This general applicable methodology was expanded to 6-deoxy and to amino sugars, too.

These chiral building blocks in hand, Lichtenthaler demonstrated their use in a number of total syntheses of natural products. In comparatively few steps (S,S)-palytazine, the absolute configuration of which had not been fully established, could be synthesized and the structure proven. The marine metabolite (S,S)-bissetone, the plant acid daucic acid, and the ACRL toxin were prominent examples to be synthesised along this scheme. 

The "ulosylbromides", 2-keto-glycosyl-bromides which were developed from the enolon-chemistry, attained special significance. Once a single step procedure from the glycal esters was established, the broad utility of this class of building blocks was shown in many total syntheses. Prominent examples were the total syntheses of the antibiotic spectinomycin and the cardiac glycoside gomphoside. The ulosylbromides opened up a simple access to oligosaccharides with ß-D-manno configuration. After his retirement, Lichtenthaler summarized the wide potential of the 2-oxo-glycosyl bromides in a review in 2011. 

Besides these building blocks, many other C-6 chiral units were made, sometimes in both enantiomeric forms, containing only one chiral centre. Those were used for the total syntheses of a number of natural products, pheromones and marine toxins. 

The methods developed on the monosaccharides were expanded to disaccharides, which were also cheaply available in large amounts, especially to sucrose. The German sugar industry collaborated with Lichtenthaler in this field for many years. This research topic was investigated very deeply by examining the conformation in solution, the surface energy potentials and the molecular electrostatic potentials. Based on these results one could predict the reactivity of these kinds of disaccharides. This part of Lichtenthaler's work continues to holt great potential for industrial applications in the future.

With the help of the MOLCAD-software, which was developed at the Technical University of Darmstadt, molecular modelling of saccharose, other disaccharides and cyclo-dextrines, mannines and galactines were performed. Valuable results regarding the conformation, the MEPs (molecular electrostatic profile), and MLPs (molecular lipophilic profile) could be generated. These results are very valuable for understanding and exploring artificial enzymes.

Frieder Lichtenthaler´s name is closely connected with the promotion of the utilisation of inexpensive, renewable carbohydrates, available in bulk scale, as chiral building blocks, and therefore the ennoblement of carbohydrates in a scientific and in an economic sense. He formed an internationally renowned competence centre for carbohydrate chemistry at the Technical University of Darmstadt in Germany. On the occasion of the 4th European Carbohydrate Symposium in Darmstadt, Lichtenthaler's contemporary and friend Prof. Leslie Hough (London) depicted this connection better than words could, in an artistic drawing of the structure of sucrose, substituting the oxygen atoms with the letters of Darmstadt.

In 1990, Lichtenthaler organised an outstanding workshop with the title "Carbohydrates as Organic Raw Materials" at the Technical University of Darmstadt. This event developed into a biannual workshop held at different universities in Europe. 

Over a span exceeding five decades, his scholarly achievements were recognized by multiple institutions. In 1973 and again in 1976 Lichtenthaler was a Distinguished Visiting Fellow of the Japan Society for the Promotion of Science. In 1985 the Royal Society of Chemistry, London named him a fellow (FRSC) and in 1994 he received the Science Award of the Sugar Processing Research Institution, New Orleans, USA. In addition to being made an Honorary Professor of Yokohama University (1992), the University of Debrecen in Hungary honoured him with a Dr. honoris causa (1993) and the Hungarian Academy of Science, Budapest, elected him an Honorary Member in 2004.

Frieder Lichtenthaler was a tireless traveller; he had a special affinity for Japan, its history and culture, as is evident from many Japanese co-workers and visiting professorships at the Keio University Tokyo (1973), the University of Kyoto (1976) and the Kanagawa University Yokohama (1992). During this period, he also became fascinated by Zen and the serenity of old Buddhist temples.

He was blessed with a fulfilling family life. His wife Evemaria, a well known architect, was a tremendous rock of support throughout his career and from this happy marriage resulted two sons (Matthias and Johannes), a daughter (Kathrin) and eventually eight grandchildren, of all of whom he was very proud. He also manifested a deep engagement with classical music, being an accomplished pianist himself.

In his final years, Lichtenthaler participated in the activities of the Clemens Schoepf Institute, was engaged in extensive refereeing for various journals and consultations with industrial companies, and took efforts to propagate the paradigm shift in chemical industry to replace petro-based raw materials with renewable ones.