Synthesis of the 5R, 8R, 9S, 11R dephosphorylated derivative of CI-920, a novel antitumor agent.

Just, George; O’Connor, Brian

doi:10.1016/s0040-4039(00)80201-4

Cited by 37 publications

(18 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar difficulties were encountered in an early synthetic study towards fostriecin, although no detailed description of the results was given. [30] At this stage we anticipated that a Stille coupling strategy, [31] which already had been successfully used to build up similar trienes, [32] would be a more promising methodology. For this purpose the dibromoalkene 21 was converted into the alkynylstannane 24 by the Corey±Fuchs protocol (Scheme 4).…”

Section: Synthesis Of the (Zze)-triene Unit-model Studiesmentioning

confidence: 99%

“…R f = 0. 30 1-(1-Ethyl-3-iodo-prop-2-ynyloxymethyl)-4-methoxy-benzene (26): AgNO 3 (166 mg, 0.98 mmol) was added in the dark to a solution of alkyne 13 (1.00 g, 4.90 mmol) and N-iodosuccinimide (1.38 g, 6.12 mmol) in acetone (40 mL) and the mixture was stirred for 4 h at room temperature. The reaction mixture was quenched with ice-cold water (100 mL) and extracted with ethyl acetate (3 î 150 mL).…”

Section: -(1-ethyl-prop-2-ynyloxymethyl)-4-methoxy-benzene (12): a 1mmentioning

confidence: 99%

See 1 more Smart Citation

Total Synthesis and Biological Evaluation of the Protein Phosphatase 2A Inhibitor Cytostatin and Analogues

Bialy

Waldmann

2004

Chemistry A European J

View full text Add to dashboard Cite

The total synthesis of the natural product cytostatin is described which inhibits protein phosphatase 2A. Cytostatin has anti-metastatic properties and induces apoptosis. On the basis of this synthesis the relative and absolute configuration of cytostatin could be assigned. Key structural elements of cytostatin are an alpha,beta-unsaturated lactone group and a side chain embodying a phosphate and a rather unstable (Z,Z,E)-triene subunit. In addition, the natural product carries six stereocenters. For the construction of the stereocenters reagent-controlled transformations were used in order to ensure maximum stereochemical flexibility. The Evans syn-aldol reaction was chosen to establish the stereochemistry at C-4, C-5, C-9 and C-10; C-6 was introduced by means of the Evans asymmetric alkylation. In all cases the same chiral auxiliary was employed as stereodirecting group. The stereocenter at C-11 was established by an asymmetric reduction using CBS-oxazaborolidine. Temporary protection of the phosphate group was achieved best by using the base-labile 9-fluorenylmethyl group, which could be cleanly cleaved by an excess of triethylamine; this reaction yielded analytically pure phosphates after a simple aqueous work-up. The (Z,Z,E)-triene embodied in cytostatin was synthesized by means of a Stille coupling as key transformation. The synthesis sequence established in this way readily gave access to a series of analogues with simplified structure. Initial biological testing of these analogues proved that the alpha,beta-unsaturated lactone, the C-11-hydroxy group and a fully deprotected phosphate moiety at C-9 are essential for the PP2A-inhibitory activity of cytostatin. The rather unstable triene moiety in the side chain can be replaced by other lipophilic residues with only moderate decrease of biological activity. Other phosphatases, that is, PP1, VHR, PTP1B, CD45, were not inhibited by cytostatin or any of the analogues, demonstrating the high selectivity of this compound. These findings will be useful for the design and synthesis of cytostatin-derived chemical tools for the study of biological processes influenced by PP2A.

show abstract

Section: Synthesis Of the (Zze)-triene Unit-model Studiesmentioning

confidence: 99%

Section: -(1-ethyl-prop-2-ynyloxymethyl)-4-methoxy-benzene (12): a 1mmentioning

confidence: 99%

Total Synthesis and Biological Evaluation of the Protein Phosphatase 2A Inhibitor Cytostatin and Analogues

Bialy

Waldmann

2004

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…46 At the outset of their endeavor, only the stereochemistry at C5 was known from the degradation experiments reported by Hokanson and French, a mere three years prior to Just’s publication. 18 The remaining three stereocenters were unassigned, resulting in eight stereoisomeric possibilities for the natural product.…”

Section: Fostriecinmentioning

confidence: 99%

“…Just and O’Connor reported the synthesis of an epimer of dephosphofostriecin in 1988 . At the outset of their endeavor, only the stereochemistry at C5 was known from the degradation experiments reported by Hokanson and French, a mere three years prior to Just’s publication .…”

Section: Fostriecinmentioning

confidence: 99%

Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products

2016

View full text Add to dashboard Cite

Fostriecin and related natural products present a significant challenge for synthetic chemists due to their structural complexity and chemical sensitivity. This review will chronicle the successful efforts of synthetic chemists in the construction of these biologically active molecules. Key carbon–carbon bond forming reactions will be highlighted, as well as the methods used to install the numerous stereocenters present in this class of compounds.

show abstract

“…The first synthetic effort toward this class of natural products was a synthesis of the C -9 epimer of dephospho-fostriecin, by Just . Not long after the discovery of its potent protein phosphatase activity, the synthetic activity around the fostriecins significantly increased.…”

mentioning

confidence: 99%

Synthesis of Dehydro-Dephospho-Fostriecin and Formal Total Synthesis of Fostriecin

Gao

O’Doherty³

2019

Org. Lett.

View full text Add to dashboard Cite

A formal synthesis of fostriecin (1) and a total synthesis of its related congener dihydro-dephospho-fostriecin 2 have been achieved. The route relies upon the use of the Sharpless dihydroxylation to set the absolute stereochemistry at C-8/9 and Noyori transfer hydrogenation and Leighton allylation to set the C-11 and C-5 relative stereochemistry, respectively. Finally, the divergent functionalization of a C-12/13 alkyne was used to establish the Z,E-dienyne of dehydrodephospho-fostriecin 2 and the Z,Z,E-triene of fostriecin (1).

show abstract

Synthesis of the 5R, 8R, 9S, 11R dephosphorylated derivative of CI-920, a novel antitumor agent.

Cited by 37 publications

References 12 publications

Total Synthesis and Biological Evaluation of the Protein Phosphatase 2A Inhibitor Cytostatin and Analogues

Total Synthesis and Biological Evaluation of the Protein Phosphatase 2A Inhibitor Cytostatin and Analogues

Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products

Synthesis of Dehydro-Dephospho-Fostriecin and Formal Total Synthesis of Fostriecin

Contact Info

Product

Resources

About