Analyses of a Mixture of Glucosyl-Cyclomaltoheptaoses Prepared on an Industrial Scale

ABSTRACT

A mixture of glucosyl-cyclomaltoheptaoses (β-cyclodextrins, βCDs) was prepared by glucoamylolysis of a mixture of maltosyl-βCDs which was produced on an industrial scale from maltose and β CD through the reverse action of Klebsiella pneumoniae pullulanase. Glucosyl-βCDs in the mixture were separated by HPLC on a reversed phase column and their molecular weights were measured by FAB-MS. In addition, the number of side-chains in each molecule was confirmed by methylation analysis and it was proved that the mixture comprised mainly of a monoglucosyl-βCD [G-β CD] and diglucosyl-β-CDs [(G)₂-βCDs], and as a minor component triglucosyl-β CDs [(G)₃-βCDs], and that G-, (G)₂-, and (G)₃-β CDs were produced in the ratios of 50%:45%:5%. The structures of three positional isomers of (G)₂-β CD were established by HPLC analysis of partial hydrolyzates, ¹³C NMR spectroscopy, and chemical synthesis. Four regioisomeric (G)₃-β CDs which could be isolated were characterized by ¹³C NMR spectroscopy.     

Synthesis of key fragments of amphidinolide Q--a cytotoxic 12-membered macrolide

β-hydroxy aldehyde and alkyl ketone moieties were effectively synthesized as key intermediates of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp.. The asymmetric center of the former derivative was produced by Sharpless asymmetric epoxidation, followed by E-selective 1,4-addition to give the sp2 methyl group. Derivatization of the L-ascorbic acid derivative by Evans asymmetric alkylation and Peterson olefination provided the latter intermediate. The coupling reaction of the segments was examined.     

Dialkylaluminum hydride-promoted cyclodimerization of silylated 1,3-enynes via skeletal rearrangement

The dialkylaluminum hydride-promoted reaction of 1-silylalk-3-en-1-ynes gave symmetrical 1,2,3,5-tetrasubstituted benzenes as single regioisomers. The novel cyclodimerization via skeletal rearrangement can be rationalized by an unprecedented mechanism involving sequential hydroalumination, alkene isomerization, carboalumination, carbon-carbon bond cleavage, and retro-hydroalumination.     

Inhibition of restriction enzymes EcoRI, BamHI and HindIII by phenethylphenylphthalimides derived from thalidomide

We discovered inhibitors of the restriction enzymes EcoRI, BamHI and HindIII by screening our library of compounds with a phenethylphenylphthalimide skeleton, based on α-glucosidase inhibitors and liver X receptor antagonists derived from thalidomide. Structural development afforded the potent restriction enzyme inhibitors 25 and 26.     

Solvation structure and stability of [(CH3)2NH]m(NH3)n-H hypervalent clusters: ionization potentials and switching of hydrogen-atom localized site

Ionization potentials (IPs) of [(CH(3))(2)NH](m)(NH(3))(n)-H hypervalent radical clusters produced by an ArF excimer laser photolysis of dimethylamine (DMA)-ammonia mixed clusters are determined by the photoionization threshold measurements. The IPs of the DMA(1)(NH(3))(n)-H hypervalent radicals decrease rapidly with the number of ammonia up to n=4, and then its decrease rate becomes much slower for n ≥ 5. This trend is very similar to that found for NH(4)(NH(3))(n) clusters. The calculated results on the stable structures and IP as well as the observed IP for DMA(1)(NH(3))(n)-H indicate that the hydrogen atom-localized site is the NH(3) moiety for n=1, while the doubly coordinated DMA-H is favorable for n=2-4, and then 4-fold-coordinated NH(4) is again more stable for n ≥ 5. These changes are consistent with the results on the femtosecond pump-probe experiments of DMA(n)-H clusters. Switching of the hydrogen atom-localized site is ascribed to the instability of DMA-H against a hydrogen-atom dissociation.     

Fluoro‐Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors

The external quenching method based on flow microreactors allows the generation and use of short‐lived fluoro‐substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated molecules using fluorinated organometallics.     

Total Syntheses of (−)‐Strictosidine and Related Indole Alkaloid Glycosides

A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α‐cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (?)‐strictosidine, which is an important intermediate in biosynthesis. This two‐step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (?)‐strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (?)‐strictosamide, (?)‐neonaucleoside A, (?)‐cymoside, and (?)‐3α‐dihydrocadambine.