Streptomyces Citricolor Nov. Sp. And a New Antibiotic, Aristeromycin

Kusaka, Taiki; Yamamoto, Hiroichi; Shibata, Motoo; Muroi, Masayuki; Kishi, Toshiharu; Mizuno, Kōmei

doi:10.7164/antibiotics.21.255

Cited by 211 publications

(88 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, biscarbonate 73 equally well provides a direct carbocyclic analogue of a nucleoside illustrated by aristeromycin 77 34 (eq 11) via the intermediacy of chiral cyclopentene 76.…”

Section: Scheme 5 Retrosynthetic Analysis Of Swainsoninementioning

confidence: 99%

Asymmetric Allylic Alkylation, an Enabling Methodology

2004

View full text Add to dashboard Cite

The diversity of mechanisms for enantiodiscrimination and of bond types that can be formed make Pd-catalyzed asymmetric allylic alkylation a powerful key step for simplification of synthetic strategy to complex molecular targets. Using a wide range of different classes of compounds including alkaloids, polyhydrofurans, nucleosides and carbanucleosides, cyclohexitols and cyclopentitols, chromanes, cyclopentanoids, amino acids, barbiturates, etc., novel synthetic strategies emerge that provide short efficient asymmetric syntheses.Chemistry distinguishes itself from the other disciplines in approaching scientific questions by its ability to design structure for function unfettered by what is available. A key enabling aspect of this freedom is the effectiveness of synthetic methodology to solve problems of selectivity, a feature that is particularly noted when dealing with biological problems. Providing efficient synthesis to complex molecules requires minimizing the number of steps, any side reactions, and purification protocols. Among the most challenging issues is obtaining enantiomerically pure compounds for which asymmetric catalysis constitutes a core competency.Among asymmetric bond forming reactions, the metalcatalyzed asymmetric allylic alkylation (AAA) is unique for several reasons.

show abstract

“…Thus, biscarbonate 73 equally well provides a direct carbocyclic analogue of a nucleoside illustrated by aristeromycin 77 34 (eq 11) via the intermediacy of chiral cyclopentene 76.…”

Section: Scheme 5 Retrosynthetic Analysis Of Swainsoninementioning

confidence: 99%

Asymmetric Allylic Alkylation, an Enabling Methodology

2004

View full text Add to dashboard Cite

show abstract

“…Specifically, we describe the synthesis and biological evaluation of the enantiomerically pure deoxy and aminodeoxy derivatives (À)-3 to (À)-12 (Table 1) and ligands (À)-13 to (+)-17, containing the carbocyclic skeleton of the natural product aristeromycin (Table 2). [9] We demonstrate a dramatic difference in activity between inhibitors with a 2'-or a 3'-deoxyribose moiety, which might be a more general phenomenon in nucleoside-based ligand binding.…”

Section: Introductionmentioning

confidence: 99%

Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

et al. 2006

View full text Add to dashboard Cite

Inhibition of the enzyme catechol O-methyltransferase offers a therapeutic handle to regulate the catabolism of catecholamine neurotransmitters, providing valuable assistance in the treatment of CNS disorders such as Parkinson's disease. A series of ribose-modified bisubstrate inhibitors of COMT featuring 2'-deoxy-, 3'-deoxy-, 2'-aminodeoxy-3'-deoxy-, and 2'-deoxy-3'-aminodeoxyribose-derived central moieties and analogues containing the carbocyclic skeleton of the natural product aristeromycin were synthesized and evaluated to investigate the molecular recognition properties of the ribose binding site in the enzyme. Key synthetic intermediates in the ribose-derived series were obtained by deoxygenative [1,2]-hydride shift rearrangement of adenosine derivatives; highlights in the synthesis of carbocyclic aristeromycin analogues include a diastereoselective cyclopropanation step and nucleobase introduction with a modified Mitsunobu protocol. In vitro biological evaluation and kinetic studies revealed dramatic effects of the ribose modification on binding affinity: 3'-deoxygenation of the ribose gave potent inhibitors (IC50 values in the nanomolar range), which stands in sharp contrast to the remarkable decrease in potency observed for 2'-deoxy derivatives (IC50 values in the micromolar range). Aminodeoxy analogues were only weakly active, whereas the change of the tetrahydrofuran skeleton to a carbocycle unexpectedly led to a complete loss of biological activity. These results confirm that the ribose structural unit of the bisubstrate inhibitors of COMT is a key element of molecular recognition and that modifications thereof are delicate and may lead to surprises.

show abstract

“…A solution of hydroxylamine hydrochloride (0.55 g, 7.91 mmol) and sodium acetate (1.2 g, 8.82 mmol) in water (3 mL) was added to the keto ester 13 (0.87 g, 4.43 mmol), and EtOH was added until dissolution was complete (20 mL 4 in THF (30 mL) and stirring the mixture vigorously for 1 h at room temperature. [20] Once prepared, 11.5 mL (22.7 mmol) of AlH 3 was added dropwise at 0°C under argon to a solution of 14 (0.5 g, 2.37 mmol) in dry THF (20 mL), and the mixture was stirred under reflux for 5 h. After addition of THF/H 2 O (1:1, 15 mL) and water (20 mL) at 0°C, stirring was continued while the mixture reached room temperature.…”

Section: (±)-Methyl 4-hydroxyimino-56-dihydro-4h-cyclopenta[b]thiophmentioning

confidence: 99%

“…[1] One major class of modified nucleosides comprises the carbocyclic nucleosides, or carbanucleosides, in which the sugar ring oxygen has been replaced by a methylene group. [2] The first member of this class was the carbocyclic analogue of adenosine described by Shealy in 1966, [3] and interest was spurred by the discovery of the antibiotic and antitumoural activities of the natural carbocyclic nucleosides aristeromycin (1) [4] and neplanocin A (2). [5] Since then, many synthetic carbanucleosides have been prepared, including the HIV-inhibitors carbovir (3) [6] and abacavir (4), [7] the latter of which is used therapeutically.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Two Precursors of Heterocarbocyclic Nucleoside Analogues

et al. 2006

View full text Add to dashboard Cite

The racemic heterobicyclic amino alcohols 6 and 7, which are of interest as intermediates in the synthesis of nucleoside analogues with heterobicyclic pseudosugars, were efficiently prepared from 2‐thienylsuccinic acid via methyl 4‐hydroxyimino‐5,6‐dihydro‐4H‐cyclopenta[b]thiophene‐6‐carboxylate [(±)‐14]. The target compounds were obtainedtogether by direct reduction of (±)‐14 with AlH3 in refluxing THF, and were separated by flash chromatography of their N‐acetylated derivatives.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

show abstract

Streptomyces Citricolor Nov. Sp. And a New Antibiotic, Aristeromycin

Cited by 211 publications

References 5 publications

Asymmetric Allylic Alkylation, an Enabling Methodology

Asymmetric Allylic Alkylation, an Enabling Methodology

Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

Synthesis of Two Precursors of Heterocarbocyclic Nucleoside Analogues

Contact Info

Product

Resources

About