有機合成における新規方法の開発とその応用

Abstract

Recent studies on the new methods and new reagents in organic synthesis developed by our laboratories have been reviewed. Their application to the synthesis of biologically intriguing natural products has been also described. Dolastatin 10 (1), a potent antitumor peptide of marine origin, has been efficiently synthesized by use of diethyl phosphorocyanidate (DEPC), diphenyl phosphorazidate (DPPA) and (+)-2-hydroxy-3-pinanone ((+)-HyPN). Mugineic acid (27), a typical phytosiderophore from barley, has been synthesized using a phenyl group as a carboxyl synthon. The method is quite efficient to produce mugineic acid on a large scale. Tilivalline (50), isolated from Klebsiella pneumoniae var. oxytoca, has been synthesized by use of DPPA as an +NH2 synthon and DEPC as a coupling reagent. The new Mannich type reaction has been explored to construct the pyrrolo [2.1-c] [1.4] benzodiazepine skeleton. The chiral phase transfer catalyst (65a) based on cinchonine has been utilized for the asymmetric hydroxylation of the α-tetralone derivatives (63). The first synthesis of the chiral ammonium fluoride (71) has been achieved, and its use for the silicon-based asymmetric aldol reaction has been accomplished. Trimethylsilyldiazomethane (TMSCHN2) has been developed as a stable and safe substitute for hazardous diazomethane. As a C1-unit introducing reagent, TMSCHN2 and its lithium salt mostly realize the reactions similar to those carried out with diazomethane. On the other hand, they generally behave as a [C-N-N] azole synthon in an analogous but not as the same way as diazomethane. Using the lithium salt of TMSCHN2, new methods for the preparation of alkynes and pyrroles have been developed.