Hydroxynitrile lyase (HNL) is a key enzyme in the catabolism of cyanogenic glycosides in higher plants. HNL catalyzes the decomposition of cyanohydrins into corresponding aldehydes or ketones and HCN for defense against predators and microorganisms. The reverse reaction, synthesis of optically active cyanohydrins, has attracted the attention of scientists and industry. We discovered several novel sources of HNL among 163 plant species in 74 families examined, using a simple HPLC-based method to determine the activity and stereoselectivity of HNLs. S-selective HNL (S-HNL) activity was found in a homogenate of the leaves of Baliospermum montanum, while R-selective HNLs (R-HNLs) were detected in the leaves and seeds of Passiflora edulis, and the seeds of Eriobotrya japonica, Prunus mume, Prunus persica, Chaenomeles sinensis and Sorbus aucuparia. The HNLs from P. edulis (PeHNL), E. japonica (EjHNL), P. mume (PmHNL), and B. montanum (BmHNL) have been purified to homogeneity and their enzymatic properties characterized. In trying to expand the applicability of the HNL-catalyzed reaction, we focused on the potential for asymmetric synthesis. We describe the efforts to develop HNL-catalyzed reactions for the optically active cyanohydrin and β-nitro alcohol synthesis.
Immunostimulating glycoconjugates from bacteria were synthesized for elucidation of the recognition with innate immune receptors. Synthesis of partial structures and analogues of lipopolysaccharide and its bioactive principle ‘lipid A’ contributed the elucidation of mode of action, i.e., interaction of lipopolysaccharide with its receptor ‘TLR4/MD-2 complex’. Immunomodulation by parasitic bacteria ‘Helicobacter pylori’ was elucidated by using synthetic lipopolysaccharide partial structures. Intracellular peptidoglycan receptors, ‘Nod1’ and ‘Nod2’, and their ligand structures were identified by using synthetic peptidoglycan partial structures. New Nod1 ligands were identified from the bacterial supernatant. In vivo function of Nod1 was studied by using synthetic ligands found from small library of Nod1 ligands.
In comparison with carbene complexes having reactive M=C double bonds, their heavier analogs, i.e. silylene and germylene complexes, having M=E (E=Si, Ge) double bonds are also expected to show high reactivity. However, most of such complexes previously prepared have actually shown poor reactivity toward usual organic substrates, probably because their M=E double bonds are sterically overprotected for stabilization. Recently, we have succeeded in synthesizing silylene and germylene complexes having hydrogen atoms on both the metal center and E atom. The M=E double bonds of these complexes are indeed the least sterically protected in any known ones and can react smoothly with various substrates such as nitriles, ketones, heterocumulenes, etc. under mild conditions. Here we report the syntheses, structures, and novel reactions of these new silylene and germylene complexes.
A design of a chiral ligand and the metal-coordinated catalyst is very important for achievement of a highly enantioselective catalytic asymmetric reactions. Recently, we developed the chiral oxazolidine ligands having N,O-acetal structure, such as phosphinooxazolidine (POZ), phosphinooxazinane (POZI) and oxazolidine (OZ). POZ and POZI afforded products in an excellent enantioselectivities in Pd-catalyzed asymmetric allylic alkylation and tandem allylation. Furthermore, cationic Pd-POZ catalysts showed high levels of catalytic activity in the asymmetric Diels-Alder (DA) reactions of some dienes with oxazolidinone- or pyrrazolidinone-type dienophiles. Cationic Pd-POZ catalyst showed an excellent catalytic activity in the DA reaction in ionic liquid (IL). The catalyst could be reused eight times without significant decrease of yield and enantioselectivity in IL/CH2Cl2 solvent system. OZ ligand also worked as organocatalyst in the DA reaction of 1,2-dihydropyridies with acroleins to afford the useful intermediate of Oseltamivir.
Aurilol (1), intricatetraol (3), and enshuol (5), marine halogen-containing members of a family of squalene-derived triterpene polyethers named oxasqualenoids, were isolated from the sea hare Dolabella auricularia, the red alga Laurencia inricata, and omaezakiana Masuda, respectively. Although their planar structures and partial configurations were elucidated by spectroscopic and chemical analyses, until now their entire configurations had not been determined. Many other types of oxasqualenoids have also been isolated from both marine and terrestrial organisms; however, it is often difficult to determine their stereostructures even by modern highly advanced spectroscopic methods, especially in the case of acyclic systems that include stereogenic quaternary carbon centers. Such systems expose the technical limitations of the current highly advanced NMR spectroscopic methods used for the structural elucidation of diverse and complex natural products. Herein, we report the total assignments of the previously incomplete stereostructures of 1, 3, and 5 to 2, 4, and 6, respectively, through the first asymmetric total syntheses featuring regioselective 5-exo and 6-endo cyclizations of bishomoepoxy alcohols.
Peptide thioesters are used as key building blocks for contemporary protein synthesis, based on the ligation strategy such as thioester method and native chemical ligation. We found the methods for preparation of the peptide thioesters, in which the key reaction is an intramolecular N-S acyl shift reaction of thiol-containing peptides. These processes can be applied to Fmoc based solid phase peptide synthesis with minimum racemization at the thioester position. For the N-S acyl shift reaction, we use an N-2-mercapto-4,5-dimethoxybenzyl (Dmmb) group on the peptide bond, or a cysteine residue. The Dmmb-containing peptide is readily converted to the corresponding 2-sulfoethyl thioester via the N-S acyl shift reaction, followed by the intermolecular thiol-thioester exchange reaction. A peptide containing a Cys-Pro ester (CPE) moiety is spontaneously transformed into a diketopiperazine (DKP) thioester under neutral conditions. Furthermore, a peptide containing a Cys-Pro-Cys (CPC) sequence was also transformed into a peptide DKP thioester under acidic conditions via the N-S acyl shift reaction.
In recent years, organic synthesis in a microflow reactor has attracted much attention. Microflow reactors have advantages over conventional batch reactors because of the short diffusion distances, improved mass and heat transfer as a result of large surface-to-volume ratios. In this short review, several remarkable examples of organic synthesis using powerful microflow technology are introduced.