Enantioselective synthesis of the dioxabicyclo[3.2.1]octane core of the zaragozic acids via intramolecular Wacker-type cyclisation reactions

Perlmutter, Patrick; Selajerern, Walailak; Vounatsos, Filisaty

doi:10.1039/b406280a

Cited by 26 publications

(19 citation statements)

References 30 publications

(12 reference statements)

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“…The route to fragment 4 commenced with the catalytic asymmetric cyclocondensation of 4-(benzyloxy)-1-butanal (13) [10] with acetyl bromide using triamine ligand 14 [11] by a modification of the procedure previously reported by Nelson et al (Scheme 3). [12] Dimethyl cuprate, generated in situ, was reacted with 15 to afford the corresponding acid, which was readily transformed into tert-butyl ester 16.…”

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confidence: 99%

Syntheses and Biological Evaluation of Iriomoteolide 3a and Analogues

2009

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Amphidinium species are an extremely prolific source of marine secondary metabolites.[1] Structurally unique polyketides such as amphidinolides, caribenolide I, and amphidinolactones have fostered the interest of chemists not only as challenging targets for total synthesis but also because of their potent anticancer activity.[2] Recently, the Amphidinium strain HYA024 was found to produce cytotoxic compounds such as iriomoteolides 1a-c, [3] and a rare 15-membered macrolide, iriomoteolide 3a (1).[4] With a novel carbon framework comprising eight stereogenic centers, four of them in allylic positions, compound 1 represents the first member of a unique and unprecedented 15-membered macrolide class. Compound 1 represents the first member of a unique and unprecedented 15-membered macrolide class. In addition, the preliminary physiological properties disclosed for 1 and its 7,8-O-isopropylidene derivative 2 are very promising, showing potent cytotoxicity against lymphoma cell lines in the low nanomolar range. [4] To confirm the assigned structure, further evaluate its biological activity, and determine whether its cellular targets are related to those of larger congeners such as amphidinolides, [5] substantial quantities of these compounds are required. Our retrosynthetic approach to 1 involved four major disconnections, which revealed key fragments 3-6 as summarized in Scheme 1. Fragment 6 was planned to be incorporated at the end of our synthetic sequence by a JuliaKocienski olefination because of its widely recognized performance in the elaboration of such sensitive settings and also to ensure a flexible late-stage diversification of the parent compound. An intermolecular esterification was envisioned to assemble fragments 3 and 4. Finally, we hypothesized that the C 2 -symmetry of the diol precursor of fragment 5 could be advantageously used to construct the 1,5-diene upon ring closure by a cross-metathesis (CM)/ringclosing metathesis (RCM) approach. We were relying on the excellent results achieved by the Grubbs-type carbene complexes in both CM and RCM processes with the expectation that the formation of a medium-sized ring would also be E,E stereoselective (Scheme 1).The required building block 3 (Scheme 2) was prepared by alkylation of the Evans oxazolidinone 7[6] with iodide 8.[7]Scheme 2. a) Na[N( , THF, 73 %; n) DDQ, CH 2 Cl 2 , pH 7 buffer, RT, 85 %. CSA = camphorsulfonic acid, DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, DIBAL-H = diisobutylaluminium hydride, DIPT = diisopropyl tartrate, DMF = N,N-dimethylformamide, DMSO = dimethylsulfoxide, MS = molecular sieves, PMB = para-methoxybenzyl, PPTS = pyridinium para-toluenesulfonate, TBAF = tetra-n-butylammonium fluoride, TBDPS = tert-butyldiphenylsilyl, TBS = tert-butyldimethylsilyl.Scheme 1. Retrosynthetic analysis for iriomoteolide 3a (1).

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Syntheses and Biological Evaluation of Iriomoteolide 3a and Analogues

2009

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“…15 The asymmetric Keck allylation 16 on 4-benzyloxybutyraldehyde 9 catalysed by (S)-BINOL gave homoallyl alcohol 10 in 80% yield with 95% ee (determined by chiral HPLC). 17 The secondary alcohol 10 was silylated to 6 using TBSCl and imidazole in 96% yield (Scheme 3).…”

Section: A R T I C L E I N F O Abstractmentioning

confidence: 99%

A practical synthesis of C14–C26 fragment of anticancer drug, eribulin mesylate

Nadella

Nayani

Mainkar

et al. 2015

Tetrahedron Letters

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“…Intramolecular Wacker-type reactions have been widely employed in the synthesis of oxygen and nitrogen heterocycles [96], For example, Widenhoefer has described the conversion of α-allyl-β−diketones to furans in the presence of a Pd(II)-catalyst and an oxidant (eq 65) [97], and Perlmutter has recently developed a strategy for the synthesis of the dioxabicyclo[3.2.1]octane core of the zaragozic acids that employs an intramolecular Wacker-type reaction (eq 66) [98]. The accepted mechanism of these transformations involves oxypalladation followed by β−hydride elimination to afford an enol ether product (eq 67), which may undergo further transformation.…”

Section: Heterocycle Synthesis Via Intramolecular Wackertype Reactionsmentioning

confidence: 99%

Recent Developments in Palladium-Catalyzed Heterocycle Synthesis and Functionalization

Wolfe¹,

Thomas²

2005

COC

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Enantioselective synthesis of the dioxabicyclo[3.2.1]octane core of the zaragozic acids via intramolecular Wacker-type cyclisation reactions

Abstract: Wacker-type cyclisation reactions provide an effective entry into the dioxabicyclo[3.2.1]octane core of the zaragozic acid analogues.

Cited by 26 publications

References 30 publications

Syntheses and Biological Evaluation of Iriomoteolide 3a and Analogues

Syntheses and Biological Evaluation of Iriomoteolide 3a and Analogues

A practical synthesis of C14–C26 fragment of anticancer drug, eribulin mesylate

Recent Developments in Palladium-Catalyzed Heterocycle Synthesis and Functionalization

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