Hapalosin isolated from Hapalosisiphon welwitschii W. & G. S. West, is a cyclic depsipeptide carrying the reversing activity against multidrug-resistance (MDR) of cancer cells acquired during chemotherapy. The 12-membered-ring structure that consists of 2-hydroxy-3-methylbutanoic acid, 3-hydroxy-2-methyldecanoic acid, and 3-hydroxy-4-(methylamino)-5-phenylpentanoic acid, adopts a 3:1 mixture of conformers related to the amide residue. From biological and stereochemical points of view, many research groups have challenged this intriguing target. This review discloses chemical investigations of hapalosin and related derivatives, as well as their biological activities.
The biomimetic constructions of fused polycyclic ethers of marine origins according to the proposals for their biogenetic pathways starting from trans-polyepoxide compounds could be realized chemically as the model experiments in two ways : one is regarded epoxy groups as electrophiles and other is those as nucleophiles.
Intramolecular domino transformations are useful for synthesizing complex compounds. On the other hand, the development of synthetically useful intermolecular multiple component domino reactions is in its infancy. The nickel-catalyzed reactions summarized in this account are among the practical intermolecular domino couplings that have been developed to date and should find wide application in organic synthesis. For instance, a variety of starting materials such as alkenes, alkynes, and unsaturated carbonyl compounds can be connected with high selectivity under reasonably mild conditions. Furthermore, an asymmetric version of the reaction is also successful.
Plaunotol, a known antiulcer drug, has antibacterial activities against Hericobacter pylori. We developed the efficient and practical synthesis of plaunotol and its derivatives. In order to construct C6-C7 tri-substituted allylic alcohol with high stereoselectivity, the Homer-Wadsworth-Emmons reaction with novel reagent and the Wittig reaction with α-acetalketones were developed. These methods were found to give a range of tri-substituted olefin moieties. Using (E)-α-bromoacrylate as a key intermediate, which was prepared from novel reagent-methyl bis (2, 2, 2-trifluoroethoxy) bromophosphonoacetate, the most effective route of plaunotol synthesis via Suzuki cross-coupling was achieved. Moreover the most practical synthesis of plaunotol was achieved via Z-selective Wittig reaction using α-acetalketone. In search for high antibacterial activities, we designed plaunotol thiourea derivatives and diol derivatives. These derivatives were synthesized regioselectively using our effective synthetic route to plaunotol. Their antibacterial activities against Hericobactor pylori are described and the C1-phenethylthiourea derivative was the most potent antibacterial agent.
Recently, there is a great demand for various chiral organic compounds with 100 % e.e. To obtain enantiopure chiral compounds and to determine their absolute configurations in an unambiguous way, it is convenient to take the method of enantioresolution employing chiral auxiliaries. We report here the development and applications of novel chiral auxiliaries powerful for both enantioresolution and determination of absolute configuration. The chiral auxiliary, (1S, 2R, 4R)- (-)-2, 10-camphorsultam 5, is useful for enantioresolution of various carboxylic acids by HPLC on silica gel and also for X-ray crystallographic determination of their absolute configurations. Furthermore, we have succeeded in extension of this strategy to various alcohols by designing a new chiral auxiliary connecting (1S, 2R, 4R)-2, 10-camphorsultam moiety and carboxylic acid group. Namely, chiral phthalic (-)-1 and dichlorophthalic (-) -2 acids were allowed to react with racemic alcohols, and the diastereomeric mixture of esters obtained was separated by HPLC on silica gel. These diastereomers generally crystallized as large prismatic crystals suitable for X-ray diffraction, and their absolute configurations could be determined by the X-ray crystallographic method using the camphor part as the internal reference of absolute configuration. The method using these chiral phthalic and dichlorophthalic acids has been applied to various racemic alcohols to obtain enantiopure alcohols and also to determine their absolute stereochemistry.
Synthesis, structure, and electronic properties of silicon chains functionalized with hypervalent silicon moieties, polar substituents, or transition metal clusters are reported. Absorption spectra of pentacoordinate silicon oligomers reveal that the introduction of pentacoordinate silicon moieties into oligosilanes leads to a drastic change of the σSiSi-σ*SiSi excitation energies. 29Si NMR spectra have proved that the conformations of pentacoordinate oligosilanes are tightly locked even in room-temperature solution. UV-VIS spectra of polysilanes having polar substituents like (alkoxycarbonyl) methyl groups suggest that polar substituents effectively promote the σ-conjugation of the silicon backbones. Electron delocalization in (-Si-Ru-Ru-Si-C6H44-) n polymers was demonstrated by the absorption spectra. Solvent-sensitive structural deformation of the Si-Ru-Ru-Si unit leads to change of the optical properties.