The ligand exchange reaction of sulfoxides with alkylmetals has been known over 40 years. However, this reaction has scarcely been received attention by chemists. This review deals with the chemistry of ligand exchange reaction of sulfoxides comprehensively and also describes recent new synthetic methods via the ligand exchange reaction. The topics in this review are as follows; 1) the discovery of the ligand exchange reaction of sulfoxides, 2) S-aryl bond-cleavage via the ligand exchange, 3) S-alkenyl bond-cleavage via the ligand exchange, 4) S-alkyl bond-cleavage via the ligand exchange and new synthetic methods, 5) generation of carbenoids via the ligand exchange and new synthetic methods, 6) overview.
A great number of protective groups for hydroxyl function have played an important role in organic synthesis particularly in the degradation or transformation of natural products and in the synthesis of polyfunctional molecules. Various types of protective groups for hydroxyl function have been exploited and are classified mostly into alkyl ether-, silyl ether-, acetal-, and ester-types. It is frequently needed to transform an existing protective group to another one pretinent to the following steps in the course of total synthesis of complex natural products such as carbohydrates and macrolide antibiotics, and this usually calls for two separate steps, i.e. a deprotection and a protection-anew. It will therefore be of great benefit in view of time and material savings to have means of one-step transformations between protective groups. From this viewpoint, I wish to demonstrate novel and efficient methods for one-step conversion of protective groups of hydroxyl function.
The molecular design and chemical synthesis of novel and artificial enediyne classes of DNA cleaving molecules 14, and their chemical and DNA cleaving profiles are described. The enediyne sulfides 1aI were synthesized via the coupling of the vinyl iodide 8 and the protected propargyl alcohol 9, and the intramolecular cyclization of the dibromide 17. 1b was found to cycloaromatize by 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) in 1, 4-cyclohexadiene through radical pathways and by a hydroxy anion in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer through a polar pathway. 1aI cleaved DNA under weakly alkaline conditions, and 1e, 1k and 1l, all of which have a DNA intercalatable moiety, exhibited strong DNA cleaving activities with the identical high purine base (G>A) selectivity. The enediyne triols 2ac were prepared from xylitol (19) via the conversion of the keto-aldehyde 24 into the keto-enediyne 25 by an intramolecular aldol reaction. 2a was also cycloaromatized in a manner similar to that for the enediyne sulfide, and 2ac showed guanine-specific DNA cleavages under weakly alkaline conditions. The enynallene sulfones 3af were obtained by m-CPBA oxidation of the corresponding enediyne sulfides. 3c was cycloaromatized by DBU through both radical and polar pathways. 3af cleaved DNA at any DNA-base site under weakly alkaline conditions, and 3df possessing a hydrophilic moiety exhibited stronger DNA cleavages. The dienediynes 4ac were synthesized from 25. 4c possessing acetoxy groups at the propargylic positions was cycloaromatized by methyl thioglycolate through radical pathways, and cleaved DNA at any pH with guanine-base selectivity. Furthermore, the DNA cleaving activity of 4c significantly increased in the presence of methyl thioglycolate.
Imidazole glycerol phosphate dehydratase (IGPD) is one of the enzymes involved in the histidine biosynthesis in plants and microorganisms, and converts imidazole glycerol phosphate (IGP) to imidazole acetol phosphate (IAP) (Fig.1). Design of inhibitors for IGPD led us to finding of a herbicidally active IRL 1803 (1 Kg/ha). Triazole phosphonate IRL 1803 is a substrate analog which strongly inhibited the IGPD purified from wheat germ in a competitive manner (Ki=10 nM). This inhibitor exhibited strong cytotoxicity in the growth test of cultured basil cells as well (I50=0.73 ppm). The cytotoxic effect was completely reversed by the addition of histidine to the cell culture medium, proving that the cytotoxicity was primarily caused by histidine starvation. Thus, a new mode of action of herbicide, “inhibition of histidine biosynthesis”, was established by discovery of inhibitors specific to IGPD.