RESUMO
The total synthesis of the natural bicyclo[3.3.0]furanolactone polyketide, plakortone Q, was achieved in 24 steps from (R)-Roche ester. The main feature of this synthetic strategy is the stereoselective construction of a central tetrahydrofuran moiety with four consecutive stereoisomeric centers using the Upjohn dihydroxylation of oxiranyl-substituted alkenes and acid-mediated 5-endo-tet cyclization.
Assuntos
Policetídeos , Ciclização , Estereoisomerismo , AlcenosRESUMO
Plakortone Q and plakdiepoxide are natural polyketides isolated from the marine sponge Plakortis simplex. Bicyclo[3.3.0]furanolactone compounds, including plakortone Q, are expected to exhibit a wide range of pharmacological activities. Therefore, developing a simple and versatile synthetic method to produce these compounds is an important research goal. We have achieved the first total synthesis of plakortone Q and plakdiepoxide through an efficient protecting-group-free strategy. The key transformation was an acid-mediated tandem 5-endo-tet/5-endo-tet cyclization of vicinal diepoxide to build the tetrahydrofuran-γ-lactone motif.
Assuntos
Policetídeos , Poríferos , Animais , Biomimética , Ciclização , Lactonas , Policetídeos/farmacologia , EstereoisomerismoRESUMO
Eiseniachloride B is a marine chlorinated oxylipin isolated from the brown alga Eisenia bicyclis. This natural product contains cyclopentane, chlorohydrin, and 14-membered lactone systems that incorporate five stereogenic centers. In this paper, we report on the total synthesis of structurally unique oxylipin eiseniachloride B from optically active lactol via ecklonialactone B in a linear sequence comprising 11 steps with a 12.1% overall yield.
Assuntos
Produtos Biológicos/síntese química , Lactonas/síntese química , Oxilipinas/síntese química , Produtos Biológicos/química , Halogenação , Lactonas/química , Conformação Molecular , Oxilipinas/química , Phaeophyceae/química , EstereoisomerismoRESUMO
Ascospiroketal B was isolated from a marine-derived fungus as a structurally unique polyketide possessing a rare tricyclic core including 5,5-spiroketal-γ-lactone. An asymmetric total synthesis of ent-ascospiroketal B was achieved using an original synthetic route. The synthesis included the stereoselective construction of 5,5-spiroketal for ascospiroketal B and stereocontrolled construction of a quaternary asymmetric carbon by rearrangement of a trisubstituted epoxide.
Assuntos
Éteres Cíclicos/síntese química , Compostos de Espiro/síntese química , Éteres Cíclicos/química , Conformação Molecular , Compostos de Espiro/química , EstereoisomerismoRESUMO
A divergent strategy has been used for the concise and efficient enantioselective formal synthesis of Annonaceous acetogenin cis-solamin. Our synthetic strategy comprises concise preparation of the diepoxyester via an 11-membered silaketal constructed by ring-closing metathesis after the dimerization of chiral epoxides, and uses an acid-catalyzed tandem intramolecular SN2-like reaction to construct the threo-cis-threo configuration of the tetrahydrofuran-diol moiety.
RESUMO
A new cyclopropane-containing sesquiterpenoid, phellilane L (1), was isolated from the medicinal mushroom Phellinus linteus ("Meshimakobu" in Japanese), a member of the Hymenochaetaceae family and a well-known fungus that is widely used in East Asia. The planar structure of 1 was determined on the basis of spectroscopic analysis. The authors achieved the first total synthesis of 1. Our protecting group-free synthesis features a highly stereoselective one-pot synthesis involving an intermolecular alkylation/cyclization/lactonization strategy for construction of the key cyclopropane-γ-lactone intermediate. Additionally, our synthesis determined the absolute configuration of phellilane L (1).
Assuntos
Agaricales/química , Basidiomycota/química , Sesquiterpenos/química , Química Farmacêutica , Estrutura MolecularRESUMO
Two new nitrogenous prenylbisabolanes never before found in Lithistid sponges have been isolated from Theonella swinhoei. These new diterpenes, named amitorine A (1) and amitorine B (2), containing a prenylbisabolane skeleton have been characterized by spectroscopic analyses, and the relative and absolute configurations of 1 and 2 were determined by asymmetric synthesis of both diastereomers via the common bicyclic lactone 6 intermediate.
Assuntos
Diterpenos/isolamento & purificação , Theonella/química , Animais , Diterpenos/química , Diterpenos/farmacologia , Japão , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
MGB polyamide-oligonucleotide conjugates ON 1-4 with linked MGB polyamides at the 2-exocyclic amino group of a guanine base using aminoalkyl linkers were synthesized and evaluated in terms of binding affinity for complementary DNA containing the MGB polyamide binding sequence using T m and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py4- and Py3-), which possess binding affinity for A-T base pairs, and imidazole (Im3-) and pyrrole-γ-imidazole (Py3-γ-Im3-) polyamide hairpin motifs, which possess binding affinity for C-G base pairs. It was found that the stability of modified dsDNA was greatly influenced by the linker length. Py4- and Py3-oligonucleotide conjugates (ON 1 (n = 4) and ON 2 (n = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im3-oligonucleotide conjugate ON 3 (n = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ON 3 (n = 4) was lower compared with the pyrrole amide moiety of ON 2 (n = 4). The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2), which possesses binding affinity for C-G base pairs via a pyrrole/imidazole combination and contains a 2-aminoethyl linker, showed high binding ability for complementary DNA. Furthermore, the DNA sequence recognition of MGB polyamide-oligonucleotide conjugates was investigated using single-base mismatch DNAs, which possess a mismatch base in the MGB polyamide binding sequence. The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2) showed high sequence recognition ability for complementary DNA.
RESUMO
This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B. The synthesis involved conjugate addition accelerated by trimethylsilyl chloride, construction of the ten-membered ring via the intramolecular SN2 reaction promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene, and osmium-mediated π-facial selective dihydroxylation to functionalize the 1,1-disubstituted alkene.
RESUMO
On the basis of reports that a minor groove binder pyrrolepolyamide can interfere with gene expression by the sequence-specific recognition of DNA, we expected that nucleoside bearing a pyrrolepolyamide would be able to regulate gene expression. Therefore, we designed and synthesized the pyrrolepolyamide-adenosine (Hybrid 1) and -2'-deoxyguanosine hybrids (Hybrid 2 and Hybrid 3) as lead compounds for gene expression control compounds. The pyrrolepolyamide frame of Hybrid 2 and Hybrid 3 combines at the 2-exocyclic amino group of the 2'-deoxyguanosine by a linker and the 2-exocyclic amino group of guanine exists in the minor groove side of the duplex. Hybrid 2 is the 2'-deoxyguanosine-pyrrolepolyamide hybrid using the 3-aminopropionyl linker, while Hybrid 3 uses the 3-aminopropyl linker. An evaluation of the DNA binding sequence selectivity was performed by analysis of T(m) values and CD spectra, using distamycin A as a contrast. Hybrid 3 has provided more excellent sequence-distinguishable ability than other hybrids and Distamycin A. Moreover, on the basis of these results, we synthesized oligonucleotides conjugated to Hybrid 4, which is stable under conditions of DNA oligonucleotide solid phase synthesis, arranged from Hybrid 3. From T(m) values and CD spectral analysis, it was found that oligonucleotides conjugating Hybrid 4 possess high recognition ability and very high binding ability for the DNA that includes the pyrrolepolyamide binding sequence.
Assuntos
Desenho de Fármacos , Expressão Gênica/efeitos dos fármacos , Nucleosídeos , Nylons , Oligonucleotídeos , DNA , Nucleosídeos/síntese química , Nucleosídeos/química , Nucleosídeos/farmacologia , Nylons/síntese química , Nylons/química , Nylons/farmacologia , Oligonucleotídeos/síntese química , Oligonucleotídeos/química , Oligonucleotídeos/farmacologiaRESUMO
Annonaceous acetogenins have a wide range of potential biological activities. The development of simple and diversity-oriented approaches to their synthesis is therefore important. We have achieved the first total synthesis of squafosacin F and assigned its absolute configuration. The key steps were an acid-mediated tandem intramolecular double cyclization to build the hydroxy-flanked mono-tetrahydrofuran core and decoration with the desired functionalities of the target natural product via highly stereoselective reactions.
RESUMO
Nucleophilic aromatic substitution of 9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-6-chloro-2-fluoro-9H-purine with N-(tert-butyldimethylsilyl) [15N]phthalimide in the presence of a catalytic amount of CsF at room temperature in DMF efficiently afforded the 6-chloro-2-[15N]phthalimidopurine derivative, which was subsequently converted to the [2-15N]guanosine derivative. The 2'-deoxy[2'-15N]guanosine derivative was also efficiently synthesized through a similar procedure.
Assuntos
Desoxiguanosina/síntese química , Guanosina/análogos & derivados , Guanosina/síntese química , Ftalimidas/química , Desoxiguanosina/química , Guanosina/química , Estrutura Molecular , Isótopos de NitrogênioRESUMO
The 6-(levulinyloxymethyl)-3-methoxy-2-nitrobenzoyl (LMMoNBz) and 2-(levulinyloxymethyl)-5-methoxy-4-nitrobenzoyl (LMMpNBz) groups were developed as novel base-labile groups for 5'-hydroxy protection in solid-phase oligonucleotide synthesis. A comparative study of the utility of LMMoNBz, LMMpNBz, and 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) groups is described.
Assuntos
Ácidos Levulínicos/química , Nitrobenzenos/química , Oligonucleotídeos/síntese química , Cromatografia Líquida de Alta Pressão , Oligonucleotídeos/químicaRESUMO
The 6-(levulinyloxymethyl)-3-methoxy-2-nitrobenzoyl (LMMoNBz) and 2-(levulinyloxymethyl)-5-methoxy-4-nitrobenzoyl (LMMpNBz) groups were developed as novel base-labile protection for the 5'-hydroxy function in solid-phase oligonucleotide synthesis. A comparative study of the LMMoNBz, LMMpNBz and 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) protecting groups for oligonucleotide synthesis proved strong feasibility for the LMMoNBz group.
Assuntos
Oligonucleotídeos/química , Oligonucleotídeos/síntese química , Cromatografia Líquida de Alta Pressão , Hidroxilação , Indicadores e Reagentes , Estrutura Molecular , Relação Estrutura-Atividade , TiminaRESUMO
An efficient synthesis of adenosine bearing pyrrolepolyamide 1 was achieved by coupling of 3 with 2. The CD spectra obtained at several [ligand ]/[duplex] ratios allowed verification of the formation complex of the DNA duplex [d(CGCAAATTGGC)/d(GCCAATTTGCG)] with 1.
Assuntos
DNA/química , Nucleosídeos/síntese química , Oligodesoxirribonucleotídeos/síntese química , Dicroísmo Circular , Modelos Moleculares , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Nucleosídeos/química , Nylons , Oligodesoxirribonucleotídeos/química , PirróisRESUMO
NMR signal assignments for DNA oligomers have been performed by the well-established sequential assignment procedures based on NOESY and COSY. The H4'/H5'/H5'' resonance region is congested and difficult to analyze without the use of isotope-labeled DNA oligomers. Here a DNA dodecamer constructed with 2'-deoxy[5'-(13)C]ribonucleotides, 5'-d(*C*G*C*G*A*A*T*T*C*G*CG)-3' (*N = [5'-(13)C]Nucleotide), was prepared in an effort to analyze the H4'/H5'/H5'' resonance region by 2D 1H-13C HMQC-NOESY. In the C5' and H1' resonance region, weak and strong cross peaks for C5'(i)-H1'(i) and C5'(i)-H1'(i-1), respectively, were found, thus enabling the sequential assignment within this region. A similar sequential assignment route was found between C5' and H2''. Proton pair distances evaluated from the canonical B-DNA as well as A-DNA indicated that these sequential-assignment routes on a 2D 1H-13C HMQC-NOESY spectrum work for most nucleic acid stem regions.
Assuntos
Oligodesoxirribonucleotídeos/química , Isótopos de Carbono , DNA/análise , Espectroscopia de Ressonância MagnéticaRESUMO
Pyrrole polyamide-2'-deoxyguanosine 5'-phosphate hybrid (Hybrid 4) was synthesized and evaluated in terms of the inhibition of mouse mammary carcinoma FM3A cell growth. Hybrid 4 was found to exhibit dose-dependent inhibition of cell growth.
Assuntos
Nucleotídeos de Desoxiguanina/síntese química , Nucleotídeos de Desoxiguanina/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Nucleotídeos de Desoxiguanina/química , Relação Dose-Resposta a Droga , Feminino , Neoplasias Mamárias Animais , Camundongos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Nylons/síntese química , Nylons/química , Nylons/farmacologia , Pirróis/síntese química , Pirróis/química , Pirróis/farmacologiaRESUMO
DNA oligonucleotide-conjugated pyrrole polyamide-2'-deoxyguanosine hybrids were synthesized and examined as novel gene expression control compounds. The T(m) values and circular dichroism spectral analyses showed that the oligonucleotide-conjugated hybrids possess high DNA recognition and a very high binding affinity for DNA that includes the pyrrole polyamide binding sequence.
Assuntos
DNA/metabolismo , Desoxiguanosina/química , Expressão Gênica/efeitos dos fármacos , Nylons/química , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/farmacologia , Pirróis/química , Desoxiguanosina/síntese química , Nylons/síntese química , Oligonucleotídeos Antissenso/síntese química , Pirróis/síntese químicaRESUMO
Pyrrolepolyamide-2'-deoxyguanosine hybrids (Hybrid 2 and Hybrid 3) incorporating the 3-aminopropionyl or 3-aminopropyl linker were designed and synthesized on the basis of previously reported results of a pyrrolepolyamide-adenosine hybrid (Hybrid 1). Evaluation of the DNA binding sequence selectivity of pyrrolepolyamide-2'-deoxyguanosine hybrids was performed by CD spectral and T(m) analyses. It was shown that Hybrid 3 possessed greater binding specificity than distamycin A, Hybrid 1 and Hybrid 2.
RESUMO
DNA oligonucleotide conjugated pyrrolepolyamide- and pyrrole-imidazole polyamide-2'-deoxyguanosine hybrids were efficiently synthesized by a post-synthetic modification method through condensation of the 2-fluoro-2'-deoxyinosine moiety of oligonucleotide 9 and FmocNH-PyXPyPy (X = Py or Im) derivatives.