Enantioselective synthesis of 1-aryl-2-propenylamines: a new approach to a stereoselective synthesis of the Taxol® side chain

Castagnolo, Daniele; Armaroli, Silvia; Corelli, Federico; Botta, Maurizio

doi:10.1016/j.tetasy.2004.01.035

Cited by 32 publications

(11 citation statements)

References 33 publications

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“…With the use of LiBH 4 or NaBH 4 (entries 1 and 2), a lower stereoselectivity of 18/17 was observed (4:1 and 7:1, respectively). The remarkable stereoselectivity in the reduction of 19 can be explained by the well-known Crams chelation model (Scheme 3); [25] the stereoselectivity was consistent with the chelation ability of alkali metal ions (K + > Na + > Li + ) to form a chelate in the proposed transition state 19A.…”

Section: Synthesis Of Segmentmentioning

confidence: 53%

Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

Narita

Kikuchi

Watanabe

et al. 2009

Chemistry A European J

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The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins A and B, 5''-epi-spiruchostatin B and FK228 were efficiently synthesized in a convergent and unified manner. The synthetic method involved the following crucial steps: i) a Julia-Kocienski olefination of a 1,3-propanediol-derived sulfone and a L- or D-malic acid-derived aldehyde to access the most synthetically challenging unit, (3S or 3R,4E)-3-hydroxy-7-mercaptohept-4-enoic acid, present in a D-alanine- or D-valine-containing segment; ii) a condensation of a D-valine-D-cysteine- or D-allo-isoleucine-D-cysteine-containing segment with a D-alanine- or D-valine-containing segment to directly assemble the corresponding seco-acids; and iii) a macrocyclization of a seco-acid using the Shiina method or the Mitsunobu method to construct the requisite 15- or 16-membered macrolactone. The present synthesis has established the C5'' stereochemistry of spiruchostatin B. In addition, HDAC inhibitory assay and the cell-growth inhibition analysis of the synthesized depsipeptides determined the order of their potency and revealed some novel aspects of structure-activity relationships. It was also found that unnatural 5''-epi-spiruchostatin B shows extremely high selectivity (ca. 1600-fold) for class I HDAC1 (IC(50)=2.4 nM) over class II HDAC6 (IC(50)=3900 nM) with potent cell-growth-inhibitory activity at nanomolar levels of IC(50) values.

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Section: Synthesis Of Segmentmentioning

confidence: 53%

Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

Narita

Kikuchi

Watanabe

et al. 2009

Chemistry A European J

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“…Table 1. Structural and biological properties of taxanes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and epothilones (15,16,(18)(19)(20)(21) used in this study location of paclitaxel binding site in the β subunit but lacked the resolution to exactly define the whole ligand conformation. As a consequence, not all the amino acid residues were well solved and paclitaxel was replaced by the X-ray structure of docetaxel.…”

Section: Resultsmentioning

confidence: 99%

“…20 Moreover, the delivery of enantiomerically pure molecules was not our priority at the moment, as the biological data for these modified taxuspine-like compounds are yet not available. Thus in the retrosynthetic analysis of 24, after appropriate protections, removal of the Taxol ® 's phenylisoserine side chain 21 and deoxygenation at the C-13 position 22 afforded a naked carbocyclic core (25), which was further simplified, leading to models 28 and 29, more easily accessible for our preliminary studies via RCM-based macrocyclization reaction and useful to optimize the synthetic procedures, as outlined in Scheme 2. …”

Section: Methodsmentioning

confidence: 99%

A pharmacophore modeling approach to design new taxol® mimics: towards the synthesis of potential anticancer and MDR-reversing agent

Renzulli¹,

Rocheblave²,

Avramova³

et al. 2006

Arkivoc

Self Cite

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The remarkable therapeutic importance of taxane diterpenoids as anticancer drugs and their challenging structural complexity have stimulated worldwide enormous efforts. Our group developed a theoretic quantitative model describing the relationship between structure and biological activity of microtubules-stabilizing anticancer agents (MSAAs) aimed at gaining an insight into the specific structural features required for the ligand-receptor binding. The model was demonstrated to be able to estimate/predict the microtubule-stabilising activity for a series of taxanes and provided further details about the influence of each pharmacophore point on the ligand binding affinity. Molecular modeling studies from our group revealed that modified Taxuspines U and X could adopt a conformation similar to the bioactive conformation of paclitaxel and can be well accommodated within the pseudoreceptor model. Following the suggestions coming from the model we rationally designed and synthesized new simplified taxuspine U analogues. In particular, we developed a new methodology for the synthesis of such compounds involving a macrocyclisation reaction via RCM in presence of different functional groups.

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“…Recently, it has been reported that b-lactams have novel biological properties such as acting as cytomegalovirus protease inhibitors [12], thrombin and tryptase inhibitors [13], cholesterol absorption inhibitors [14], human leukocyte elastease (HLE) inhibitors [15], porcine pancreatic elastease (PPE) inhibitors [16], HIV-1 protease [17], and peroxisome proliferator-activated receptors (PPARs) [18]. Besides their biological activities, the importance of b-lactams as synthetic intermediates has been widely recognized in organic synthesis [19] for example in the semi-synthesis of Taxol [20]. Like azetidinone, coumarin also exhibits diverse biological properties [21].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, in‐vitro Antimicrobial and Cytotoxic Studies of Novel Azetidinone Derivatives

Keri¹,

Hosamani²,

Reddy³

et al. 2010

Archiv der Pharmazie

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Developing novel antimicrobial drugs is increasingly important in the modern pharmaceutical industry. A series of novel 3-chloro-4-[4-(2-oxo-2H-chromen-4-ylmethoxy)phenyl]-1-phenylazetidin-2-ones 5a-o have been synthesized from 4-bromomethylcoumarins 1a-e and 4-aryliminomethyl-phenols 3a-c. These compounds were screened for their in-vitro antibacterial activity against two Gram-positive (Staphylococcus aureus and Vancomycin resistant enteroccoccus) and two Gram-negative (Escherichia coli and Shigella dysentery) bacterial strains and antifungal activity against Aspergillus fumigatus, Candida albicans, and Penicillium. Results revealed that compounds 5c, 5f, 5h, 5j, and 5m showed excellent activity against a panel of microorganisms. The brine-shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and two compounds, 5h and 5m, possessing LD(50) = 7.154x10(-4 )M and 5.782x10(-4) M, respectively, displayed potent cytotoxic activity against Artemia salina. The presence of a chlorine group in the coumarin moiety, its effect on their antibacterial, antifungal, and cytotoxic activities is discussed. All newly synthesized compounds were characterized by elemental analysis, IR, (1)H-NMR,( 13)C-NMR, and MS.

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Enantioselective synthesis of 1-aryl-2-propenylamines: a new approach to a stereoselective synthesis of the Taxol® side chain

Cited by 32 publications

References 33 publications

Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B, FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

A pharmacophore modeling approach to design new taxol® mimics: towards the synthesis of potential anticancer and MDR-reversing agent

Synthesis, in‐vitro Antimicrobial and Cytotoxic Studies of Novel Azetidinone Derivatives

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