134440-89-4Relevant academic research and scientific papers
Facile and rapid access to linear and truncated microcystin analogues for the implementation of immunoassays
Clave,Ronco,Boutal,Kreich,Volland,Franck,Romieu,Renard
experimental part, p. 676 - 690 (2010/05/02)
A series of simplified microcystin-LR analogues based on Adda [(2S,3S,8S,9S,4E,6E)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldecadienoic acid] or its corresponding aldol precursor linked to a polypeptide moiety have been synthesised and assessed for thei
Enantioselective synthesis of the protein phosphatase inhibitor (-)-motuporin
Hu, Tao,Panek, James S.
, p. 11368 - 11378 (2007/10/03)
A highly convergent asymmetric synthesis of the protein phosphatase inhibitor motuporin 1a is described. Synthesis and coupling of the individual peptide fragments [34 + -35 → 51] followed by macrocyclization afforded the fully protected motuporin precursor 33, which is converted to the natural product by dehydration and ester hydrolysis, Six of the eight stereogenic centers associated with the natural product were introduced using asymmetric crotylsilane bond construction methodology. Our approach features an efficient Pd(0)-catalyzed cross-coupling reaction between a configurationally well-defined vinyl zinc intermediate 22 and an (E)-vinyl iodide 7, which afforded compound 43, resulting in the construction of the trisubstituted (E,E)-diene system of the motuporin side chain. Improved reaction conditions for macrocyclization in the formation of 33 are also detailed.
Total synthesis of motuporin (nodularin-v)
Bauer, Shawn M.,Armstrong, Robert W.
, p. 6355 - 6366 (2007/10/03)
The serine/threonine phosphatase (protein phosphatase 1 and 2A) inhibitors constitute a biologically and structurally interesting class of natural products. Among this class of inhibitors are cyclic pentapeptides (nodularins) and cyclic heptapeptides (mic
An asymmetric synthesis of ADDA, and ADDA-glycine dipeptide using the ss-lactam synthon method
Cundy, Darren J.,Donohue, Andrew C.,McCarthy, Tom D.
, p. 559 - 567 (2007/10/03)
The paper describes the synthesis of the W-Boc lactam 4, and demonstrates that it is an important intermediate in the synthesis of dipeptide 5 (X = H, n = 0, R = Me), an analogue of the ADDA-GIu dipeptide 3. In addition we have described a mild method for the preparation of the amino acid salt ADDA-HC1, and provided synthetic methods, and full characterisation for the previously 'elusive' free amino acid ADDA.
Total synthesis of motuporin and 5-[L-Ala]-motuporin
Samy, Raghu,Kim, Hong Yong,Brady, Matthew,Toogood, Peter L.
, p. 2711 - 2728 (2007/10/03)
Total synthesis of the cyclic peptide hepatotoxin motuporin is described, including an efficient synthesis of the constituent amino acid Adda. Three strategies to motuporin are outlined with their relative strengths and weaknesses. Cyclization of the linear peptide precursor was found to proceed moderately well for peptides containing the N- methyldehydrobutyrine residue masked as a threonine, but significant C- terminal epimerization occurred in the presence of the dehydroamino acid. Replacement of the N-methyldehydrobutyrine residue by L-alanine was explored to assess the contribution of this dehydroamino acid to the biochemical activity of motuporin. Some epimerization also was observed during cyclization of the alanine-containing peptide. Synthetic motuporin and both isomers of 5-[L-Ala]-motuporin inhibit the activity of protein phosphatase-1 (PP1) in rat adipocyte lysates with comparable IC50 values. These results indicate that the N-methyldehydrobutyrine residue is not essential for PP1 inhibition.
Towards an asymmetric synthesis of ADDA conjugates
Cundy, Darren J.,Donohue, Andrew C.,McCarthy, Tom D.
, p. 5125 - 5128 (2007/10/03)
In order to develop a general synthesis of ADDA containing peptides, an asymmetric synthesis of the β-lactum 4 and initial investigations into its opening with aminoesters is described.
A new stereoselective route to (2S, 3S, 8S, 9S, 4E, 6E)-3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid (Adda)
Kim, Hong Yong,Toogood, Peter L.
, p. 2349 - 2352 (2007/10/03)
N-Boc-Adda has been prepared in 15 steps and 9% overall yield from the readily available alcohol, 3-pentyne-2-ol, employing a route that includes two Claisen rearrangements.
Total synthesis of the serine-threonine phosphatase inhibitor microcystin-LA
Humphrey, John M.,Aggen, James B.,Chamberlin, A. Richard
, p. 11759 - 11770 (2007/10/03)
Reversible protein phosphorylation, which is mediated by kinases and phosphatases, is a major control element of the cell. There is a diverse group of toxic natural products that inhibit certain phosphatases, thereby disrupting normal biochemical pathways
Stereocontrolled Synthesis of (2S,3S,8S,9S,4E,6E)-3-Amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic Acid (Adda), the Amino Acid Characteristic of Microcystins and Nodularin
Beatty, Mark F.,Jennings-White, Clive,Avery, Mitchell A.
, p. 1637 - 1642 (2007/10/02)
(4R,5S)-4-Methyl-5-phenyloxazolidin-2-one has been used as a chiral template to construct the 8S and 9S chiral centres of (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda), the 2S and 3S centres being derived from D-asp
