Synthesis of the proposed core of aeruginosins 205: the new α-amino acid (2S,3aS,6R,7aS)-2-carboxy-6-chlorooctahydroindole

Valls, Nativitat; Vallribera, Merce; Font-Bardı́a, Mercè; Soláns, Xavier; Bonjoch, Josep

doi:10.1016/s0957-4166(03)00170-8

Cited by 21 publications

(9 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analysis of gHMBC and 1D TOCSY data then established that 2 was bearing an agmatine rather than an Aeap moiety. Thus, the structure of 2 closely resembles the recently revised structure of aeruginosin 205 [28]. The absolute stereochemistry of the phenyl lactic acid and the leucine moiety of 1 was determined after acid hydrolysis by chromatography on chiral stationary phase and comparison of retention times to those of authentic standards.…”

Section: Resultsmentioning

confidence: 62%

Biosynthesis and Structure of Aeruginoside 126A and 126B, Cyanobacterial Peptide Glycosides Bearing a 2-Carboxy-6-Hydroxyoctahydroindole Moiety

Ishida

Christiansen

Yoshida

et al. 2007

Chemistry & Biology

105

168

View full text Add to dashboard Cite

Aeruginosins represent a group of peptide metabolites isolated from various cyanobacterial genera and from marine sponges that potently inhibit different types of serine proteases. Members of this family are characterized by the presence of a 2-carboxy-6-hydroxyoctahydroindole (Choi) moiety. We have identified and fully sequenced a NRPS gene cluster in the genome of the cyanobacterium Planktothrix agardhii CYA126/8. Insertional mutagenesis of a NRPS component led to the discovery and structural elucidation of two glycopeptides that were designated aeruginoside 126A and aeruginoside 126B. One variant of the aglycone contains a 1-amino-2-(N-amidino-Delta(3)-pyrrolinyl)ethyl moiety at the C terminus, the other bears an agmatine residue. In silico analyses of the aeruginoside biosynthetic genes aerA-aerI as well as additional mutagenesis and feeding studies allowed the prediction of enzymatic steps leading to the formation of aeruginosides and the unusual Choi moiety.

show abstract

Section: Resultsmentioning

confidence: 62%

Biosynthesis and Structure of Aeruginoside 126A and 126B, Cyanobacterial Peptide Glycosides Bearing a 2-Carboxy-6-Hydroxyoctahydroindole Moiety

Ishida

Christiansen

Yoshida

et al. 2007

Chemistry & Biology

105

168

View full text Add to dashboard Cite

show abstract

“…First, cultures of Oscillatoria agardhii obtained in Japan are known to produce aeruginosin 205A, which was originally proposed to contain a 6 R -chloro substitutent in the octahydroindole-2-carboxylic acid subunit. However, this structural assignment has been questioned on the basis of definitive synthesis of the proposed 2-carboxy-6-chlorooctahydroindole ).…”

Section: Introductionmentioning

confidence: 99%

TheN-Acyloxyiminium Ion Aza-Prins Route to Octahydroindoles: Total Synthesis and Structural Confirmation of the Antithrombotic Marine Natural Product Oscillarin

2004

View full text Add to dashboard Cite

The first enantiocontrolled total synthesis of the marine natural product oscillarin is described. The proposed structure and absolute configuration of oscillarin is thus confirmed, and a previously assigned structure of a subunit was shown to be incorrect. The X-ray structure of an oscillarin-thrombin complex was resolved at 2.0 A resolution, which validated its potent inhibitory activity against the enzyme with an IC(50) = 28 nM. Methodology was developed for the synthesis of enantiopure octahydroindole-2-carboxylic acids with usable functionality at C-6. The method consists of the halocarbocyclization of N-acyloxyiminium ions containing an olefinic tether in the presence of tin tetrachloride or tin tetrabromide. This N-acyloxyiminium ion aza-Prins carbocyclization proved to be general for the construction of octahydroindole and perhydroquinoline 2-carboxylic acids. Mechanistic rationales are based on an antiperiplanar attack of the terminal alkene on the iminium ion, leading to an incipient secondary carbocation which is trapped by halide via an equatorial attack. X-ray crystal structures of products corroborate the expected stereochemistry.

show abstract

“…The IC 50 value of purified 1h was found to be 0.035 μg/mL, that is, in good accordance with the above result. Although there is no sulfate ester in 1h , 1h is as potent as Agma-containing sulfated aeruginosins 205-A and B …”

Section: Resultsmentioning

confidence: 99%

Solid-Phase Combinatorial Synthesis of Aeruginosin Derivatives and Their Biological Evaluation

et al. 2006

View full text Add to dashboard Cite

show abstract

Synthesis of the proposed core of aeruginosins 205: the new α-amino acid (2S,3aS,6R,7aS)-2-carboxy-6-chlorooctahydroindole

Cited by 21 publications

References 8 publications

Biosynthesis and Structure of Aeruginoside 126A and 126B, Cyanobacterial Peptide Glycosides Bearing a 2-Carboxy-6-Hydroxyoctahydroindole Moiety

Biosynthesis and Structure of Aeruginoside 126A and 126B, Cyanobacterial Peptide Glycosides Bearing a 2-Carboxy-6-Hydroxyoctahydroindole Moiety

TheN-Acyloxyiminium Ion Aza-Prins Route to Octahydroindoles: Total Synthesis and Structural Confirmation of the Antithrombotic Marine Natural Product Oscillarin

Solid-Phase Combinatorial Synthesis of Aeruginosin Derivatives and Their Biological Evaluation

Contact Info

Product

Resources

About