Total Synthesis of Amphidinolide T4

Fürstner, Alois; Aïssa, Christophe; Riveiros, Ricardo; Ragot, Jacques P.

doi:10.1002/anie.200290042

Cited by 84 publications

(40 citation statements)

References 47 publications

(15 reference statements)

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“…The first total synthesis of amphidinolide T4 (161), a natural compound with a pronounced cytotoxicity against various cancer cell lines, has been achieved using the second generation NHC ruthenium complex 33 in order to close the 19-membered lactone core. 85 Hydrogenation, olefination and further deprotection of the intermediate compounds finally gave synthetic amphidinolide T4 having all characteristics in excellent agreement with those of the natural compound.…”

Section: 156mentioning

confidence: 75%

N-Heterocyclic carbenes as highly efficient ancillary ligands in homogeneous and immobilized metathesis ruthenium catalytic systems

Drăguţan¹,

Drăguţan²,

Delaude

et al. 2005

Arkivoc

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Dedicated to Professor Alexandru T. Balaban on the occasion of his AbstractThis general overview focuses on novel N-heterocyclic carbene (NHC) Ru complexes, now at the forefront of research in metathesis chemistry, and on their derived multiple applications in targeted organic, polymeric and natural compound synthesis. This outstanding, large class of ruthenium precatalysts combines high activity and selectivity with increased stability and good tolerance towards organic functionalities, air and moisture. The NHC ancillary ligands allow manipulation of the catalytic performance through adjustment of electronic and steric parameters in the ruthenium coordination sphere, facilitate introduction of chiral motifs, and enable convenient immobilization of homogeneous initiators onto solid supports. A broad spectrum of practical applications is discussed.

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Section: 156mentioning

confidence: 75%

N-Heterocyclic carbenes as highly efficient ancillary ligands in homogeneous and immobilized metathesis ruthenium catalytic systems

Drăguţan¹,

Drăguţan²,

Delaude

et al. 2005

Arkivoc

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“…122) while the pyridine nitrogen is complexed to either palladium or platinum [386]; (10) formation of macrocyclic rings (e.g. 123) for total synthesis of epothilone and structural analogs [387][388][389][390]; (11) formation of a macrocycle-bridged tetrasaccharide derivative [391]; (12) formation of an 11-membered ring (124) through RCM of a disubstituted alkene and a trisubstituted alkene [392]; (13) formation of a macrocyclic lactone for amphidinolide T4 total synthesis [393]; (14) establishment of a tethering chain between a phosphate ester and the base of a nucleoside derivative (see e.g. 125) [394,395]; (15) derivatives [396]; (16) synthesis of a macrocyclic lactone from a heptaene derivative (e.g.…”

Section: Ring Closing Metathesismentioning

confidence: 99%

The chemistry of the carbon–transition metal double and triple bond: annual survey covering the year 2002

Herndon

2004

Coordination Chemistry Reviews

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“…3b Total syntheses of amphidinolide T1-T4 have been completed by many research laboratories including ours. [4][5][6][7][8] Among these accomplishments, Fürstner and co-workers took a DTS approach to amphidinolide T1, T3, and T4 by using two acyclic stereochemically and regioselectively differentiated 12, 13-diol derivatives. 1d Scheme 1 Structures of amphidinolide T1 (1), T3 (2), and T4 (3) and the common (12E)-cycloalkene intermediate 4…”

mentioning

confidence: 99%

Concise Diverted Total Synthesis of Amphidinolide T1 and T4 from a (12E)-Cycloalkene by Selective Functionalization of the C12-C13 Double Bond

Sun¹,

Wu²,

Wu³

et al. 2011

Synlett

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Starting from a 19-membered (12E)-cycloalkene prepared by ring-closing metathesis, amphidinolide T1 and T4 were efficiently synthesized via a short sequence of selective functionalization. The key steps highlighted stereoselective dihydroxylation of the (E)-C12-C13 double bond and highly regioselective silylation/desilylation of the (12S,13S)-diol. In particular, a significant solvent effect was discovered for suppressing 1,4 O→O silyl migration or disilylation during selective mono-silylation of the (12R,13R)-and (12S,13S)-diols in toluene. In combination with our previous synthesis of amphidinolide T3, the same (12E)-cycloalkene serves as an advanced common intermediate for concise diverted total synthesis of amphidinolide T family of marine macrolides.Diverted total synthesis (DTS) has been emerging as a research frontier in chemistry and biology with aiming at decoding the structure-function relationship of natural products through synthesizing libraries of analogues from advanced intermediates and elucidating/optimizing their pharmacophoric space. 1 Efforts in DTS have yielded numerous successful natural product based or inspired drugs such as anticancer agents. 1b In parallel the concept of DTS should be applicable for the synthesis of natural products that share a similar or the same core structural unit from an advanced intermediate of lesser structural complexity. Being isolated from symbiotic marine dinoflagellate Amphidinium sp., 2,3 the amphidinolide T series of marine macrolides highlight such a case that all five congeners (T1-T5) possess a common tetrahydrofuran-containing 19-membered macrolide core. Shown in Scheme 1 are amphidinolide T1 (1), T3 (2), and T4 (3) which are either the regioisomers of the a-hydroxy ketone functionality at C12 and C13 positions (T1 vs. T3) or C12-OH (T3 vs. T4) and C14-Me (T4 vs. T5; structure not shown) epimers, respectively. In addition, amphidinolide T2 differs from T3 only on the side chain by having an extra stereogenic center at C21 position. Cytotoxicity was reported for amphidinolide T1-T4 with IC 50 values of 18, 10, 7.0, and 11 mg/ mL, and 35, 11.5, 10, and 18 mg/mL, respectively, against murine lymphoma L1210 and human epidermoid carcinoma KB cell lines. 3b Total syntheses of amphidinolide T1-T4 have been completed by many research laboratories including ours. 4-8 Among these accomplishments, Fürstner and co-workers took a DTS approach to amphidinolide T1, T3, and T4 by using two acyclic stereochemically and regioselectively differentiated 12,13-diol derivatives. 1d Scheme 1 Structures of amphidinolide T1 (1), T3 (2), and T4 (3) and the common (12E)-cycloalkene intermediate 4In our recent total synthesis of amphidinolide T2 and T3, we envisioned a DTS strategy based on a ring-closing metathesis (RCM) 9 and asymmetric dihydroxylation (AD) 10 sequence. The 19-membered ring (12E)-cycloalkene 4 and an analogue with a different side chain were first assembled via RCM 11 and were then subjected to selective functionalization via AD and post-AD transformations to i...

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Total Synthesis of Amphidinolide T4

Abstract: Organometallic chemistry in general and catalysis in particular are used in the first total synthesis of amphidinolide T4 (see scheme); a prototype member of a series of macrolide antibiotics of marine origin with rings containing an odd number of carbon atoms.

Cited by 84 publications

References 47 publications

N-Heterocyclic carbenes as highly efficient ancillary ligands in homogeneous and immobilized metathesis ruthenium catalytic systems

N-Heterocyclic carbenes as highly efficient ancillary ligands in homogeneous and immobilized metathesis ruthenium catalytic systems

The chemistry of the carbon–transition metal double and triple bond: annual survey covering the year 2002

Concise Diverted Total Synthesis of Amphidinolide T1 and T4 from a (12E)-Cycloalkene by Selective Functionalization of the C12-C13 Double Bond

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