Imagination and creation: 1-Hydroxyindole chemistry and the dream challenge

Abstract

We have had five dreams to challenge through our life. To meet our end, we needed imaginary compounds, 1-hydroxytryptophans. This review describes how we had conceived the 1-hydroxyindole hypothesis, how we created a general synthetic method for 1-hydroxyindoles after 20 years' research, and how we have developed the chemistry of 1-hydroxytryptophans with full of new findings and discoveries. During the period, we defined "the efficient synthesis" and "the ideal synthesis" consisting of originality rate (OR), intellectual property factor (IPF), and application potential factor (APF). For evaluating the originality and the efficiency of the synthetic research, these indexes are more effective than both citation index and impact factor. Taking advantage of our 1-hydroxyindole chemistry, we have achieved three "ideal syntheses" approximately with high OR, IPF, and APF values. The methods employ only conventional reagents and reaction conditions without using any protecting groups. These methods made possible to produce such intellectual properties as leads for an α2-blocker, an inhibitor of platelet aggregation, an anti-osteoporosis agent, and a promising medicine for combating desertification, changing Gobi desert to the tract with full of green plants. These would be suitable for realizing our five dreams. Chemical conversion of enmein to gibberellin A15, four-step total synthesis of optically active ergot alkaloids, and various new reactions for the synthesis of 4-substituted indoles are also involved. © 2008 The Pharmaceutical Society of Japan.