Synthesis of 3-hydroxyindolin-2-one alkaloids, (±)-donaxaridine and (±)-convolutamydines A and E, through enolization-Claisen rearrangement of 2-allyloxyindolin-3-ones

Claisen rearrangement triggered by enolization of 2-allyloxyindolin-3-ones with DBU was performed in order to prepare 3-allyl-3-hydroxyindolin-2-ones. Total synthesis of 3-hydroxyindolin-2-one alkaloids, (±)-donaxaridine, as well as (±)-convolutamydines A and E, was achieved by transformation of the allyl moiety of 3-allyl-3-hydroxyindolin-2-ones.     

Efficient synthesis of CCR5 antagonist, 2,3-dihydro-1-benzothiepine derivatives by improved intramolecular Claisen type reaction using dialkylcarbonate

The efficient synthesis of 2,3-dihydro-1-benzothiepine derivatives 4 has been developed. The intramolecular Claisen type reaction of the new products, 4-(o-formylphenylthio)butyrate 9, with alcoholate in dialkylcarbonate as a solvent afforded 4 in good yields. According to this new procedure, we have accomplished the practical preparation of CCR5 antagonist 1 as a candidate for oral HIV-1 therapy.     

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

This review covers the literature on simple indole alkaloids and those with a nonrearranged monoterpenoid unit from the beginning up to the end of 2004. Newly isolated alkaloids, structure determinations, total synthesis and biological activities are included.     

Enantioselective total synthesis of (−)-pseudophrynaminol through tandem olefination, isomerization and asymmetric Claisen rearrangement

A new and efficient total synthesis of (−)-pseudophrynaminol, the pyrrolo[2,3-b]indole alkaloid bearing the allylic moiety at the 3a-position, has been achieved by a sequence involving 3-allylindol-2-one 8 as a key intermediate. The enantioselective construction of the quaternary carbon in 8 was performed through a tandem cascade reaction of 2-allyloxyindolin-3-one 4, olefination, isomerization, and asymmetric Claisen rearrangement.     

Fluorogenic probes for detecting deacylase and demethylase activity towards post-translationally-modified lysine residues

Reversible enzymatic post-translational modification of the ε-amino groups of lysine residues (e.g. N-acylation reactions) plays an important role in regulating the cellular activities of numerous proteins. This study describes how enzyme catalyzed N-deprotection of lysine residues of non-fluorescent peptide-coumarin probes can be used to generate N-deprotected peptides that undergo spontaneous O- to N-ester transfer reactions (uncatalyzed) to generate a highly fluorescent N-carbamoyl peptide. This enables detection of enzyme catalyzed N-deacetylation, N-demalonylation, N-desuccinylation and N-demethylation reactions activities towards the N-modified lysine residues of these probes using simple ‘turn on’ fluorescent assays.

We developed “turn-on” fluorescent probes that detect enzymatic lysine deacylation and demethylation critical for epigenetic and other cellular phenomena, using intramolecular O- to N-ester transfer reactions.     

Two new acylated flavanone glycosides from the leaves and branches of Phyllanthus emblica

Two new acylated flavanone glycosides, (S)-eriodictyol 7-O-(6"-O-trans-p-coumaroyl)-beta-D-glucopyranoside (1) and (S)-eriodictyol 7-O-(6"-O-galloyl)-beta-D-glucopyranoside (2) were isolated from the leaves and branches of Phyllanthus emblica together with a new phenolic glycoside, 2-(2-methylbutyryl)phloroglucinol 1-O-(6"-O-beta-D-apiofuranosyl)-beta-D-glucopyranoside (3), as well as 22 known compounds. Their structures were determined by spectral and chemical methods.     

Chromium- and tungsten-triggered valence isomerism of cis-1-acyl-2-ethynylcyclopropanes via [3,3]sigmatropy of (2-acylcyclopropyl)vinylidene-metal intermediates.

The reaction of cis vicinal acetylethynylcyclopropanes 1 with a catalytic amount of M(CO)5(THF) (M = Cr or W) in the presence of Et3N at room temperature gave ortho-substituted phenols 7 in good yields as valence isomerized products. In the absence of Et3N the reactions did not work at all. The reaction of a cyclopropane having an ester or an amide instead of an acetyl moiety with M(CO)5(THF) did not take place, whereas an ethynylvinylcyclopropane gave a mixture of 1- and 2-substituted 1,3,5-cycloheptatrienes. These valence isomerization reactions are assumed to proceed via the formation of vinylidene-metal intermediates 2 from terminal alkynyl moieties followed by [3,3]sigmatropy of 2 to give seven-membered carbene complexes 3.     

Finding of remarkable synergistic effect on the aroxyl-radical-scavenging rates under the coexistence of α-tocopherol and catechins

Measurements of aroxyl radical (ArO^•)-scavenging rate constants () of antioxidants (AOHs) (α-tocopherol (α-TocH) and three catechins (CatHs) (ie, epicatechin (EC), epigallocatechin (EGC), and epigallocatechin gallate (EGCG)) were performed in ethanol solution, using stopped-flow spectrophotometry. values were measured not only for each AOH, but also for the mixtures of two AOHs (α-TocH and CatH). A notable synergistic effect that the value of α-TocH increases 1.29, 1.84, and 1.65 times under the coexistence of constant concentrations of EC, EGC, and EGCG, respectively, was observed for the solutions including α-TocH and CatH. Similarly, values of CatHs (EC, EGC, and EGCG) increased 1.72, 2.25, and 2.34 times under the coexistence of constant concentrations of α-TocH, respectively. UV-Vis absorption of α-tocopheroxyl radical (α-Toc^•) (λ_max = 428 nm), which had been produced by reaction of α-TocH with ArO^•, decreased remarkably under the coexistence of α-TocH and CatHs due to the fast α-TocH-regeneration reaction by CatHs. The result suggests that the prooxidant reaction due to α-Toc^• is suppressed by the coexistence of CatHs. By analyzing the formation and decay curves of α-Toc^•, it has been ascertained that one molecule of EGCG having three OH groups at B-ring may rapidly regenerate three molecules of α-Toc^• to α-TocH.     

Synthesis of N3-substituted uridine and related pyrimidine nucleosides and their antinociceptive effects in mice

Seventy eight N(3)-substituted derivatives of uridine (1), thymidine (2), 2'-deoxyuridine (3), 6-azauridine (4), 2',3'-O-isopropylideneuridine (5), and arabinofuranosyluracil (6) were synthesized and their antinociceptive effects were evaluated. N(3)-(2',4'-Dimethoxyphenacyl)uridine (1l), N(3)-(2',4'-dimethoxyphenacyl)2'-deoxyuridine (3l), and N(3)-(2',5'-dimethoxyphenacyl)arabinofuranosyluracil (6m) possessed 93, 86, and 82% of the antinociceptive effects tested by hot plate, respectively. The antinociceptive effects of three derivatives were 5.8, 5.4, and 5.1-folds of the effect of N(3)-phenacyluridine (1h) (16%), respectively. The structure-activity relationship of N(3)-substituted pyrimidine nucleosides was also discussed.