8 CH2CO2H HOCCO2H CH2CO2H 1.9 1.5.2 Fungal Metabolites 1900-1940 Mycophenolic acid.which is now used as an immunosuppressant to prevent organ rejection after transplant operations,was first isolated by Gosic from a Penicillium species in 1896.It was s ubsea uently isolated from p stoloniferum by Alsberg and Black in 1913 and fror P hr However,its structure(1.10)was not final simpler fumaric acid was isolated by Ehrlich in 1911 from Mucor stolonifer.The fungus Aspergillus oryzae is used in Japan to produce the koji fermentation of rice to make sake.Kojic acid,5-hydroxy-2-hydroxymethyl-4-pyrone(1.11),was first isolated from this organism in 1907 and its structure was established by Yabuta in 1924.The anti-bacterial agent penicillic acid was isolated from Penicillium puberulum by Alsberg and Black in 1910.Its structure (1.12)was established in 1936 by Raistrick,who had obtained it from P.cyclopium OH OH Meo HOCH O 1.10 1.11 1.12 The First World War saw the development of the bacterial fermentation of r the produ on of aceto d butanol.This pro studies on the effect of the composition of the medium on metabolite production. e.g.by Aspergillus niger,leading to the isolation of D-gluconic acid lactone(1.13)by Malliard in 1923.This compound had previously been obtained by Herrick and May from Penicilliiom luteum in 1912.Commercial fermentation methods using a chiral acetoin condensation mediated by the yeast,Saccharomyces cerevisiae,were developed in 1930 for the synthesis of (-)-ephedrine from benzaldehyde. CH OH HO- 1.13 During the 19th and early 20th centuries there had been several reports of poisoning arising from mouldy wall paper.In a study of microbiologicalHOCCO2H CH2CO2H CH2CO2H 1.9 1.5.2 Fungal Metabolites 1900–1940 Mycophenolic acid, which is now used as an immunosuppressant to prevent organ rejection after transplant operations, was first isolated by Gosic from a Penicillium species in 1896. It was subsequently isolated from P. stoloniferum by Alsberg and Black in 1913 and from P. brevicompactum in 1932 by Raistrick. However, its structure (1.10) was not finally established until 1952. The much simpler fumaric acid was isolated by Ehrlich in 1911 from Mucor stolonifer. The fungus Aspergillus oryzae is used in Japan to produce the koji fermentation of rice to make sake´. Kojic acid, 5-hydroxy-2-hydroxymethyl-4-pyrone (1.11), was first isolated from this organism in 1907 and its structure was established by Yabuta in 1924. The anti-bacterial agent penicillic acid was isolated from Penicillium puberulum by Alsberg and Black in 1910. Its structure (1.12) was established in 1936 by Raistrick, who had obtained it from P. cyclopium. O HO2C MeO OH O 1.10 O O OH HOCH2 1.11 1.12 O MeO HO O The First World War saw the development of the bacterial fermentation of Clostridium acetobutylicum for the production of acetone and butanol. This pro￾vided a stimulus to microbiological chemistry. During the 1920s there were several studies on the effect of the composition of the medium on metabolite production, e.g. by Aspergillus niger, leading to the isolation of D-gluconic acid lactone (1.13) by Malliard in 1923. This compound had previously been obtained by Herrick and May from Penicillium luteum in 1912. Commercial fermentation methods using a chiral acetoin condensation mediated by the yeast, Saccharomyces cerevisiae, were developed in 1930 for the synthesis of L-(–)-ephedrine from benzaldehyde. O HO HO OH CH2OH O 1.13 During the 19th and early 20th centuries there had been several reports of poisoning arising from mouldy wall paper. In a study of microbiological 8 Chapter 1