Total synthesis of (+)-phorboxazole A, a potent cytostatic agent from the sponge Phorbas sp.

Pattenden, Gerald; González, Miguel A.; Little, Paul B.; Millan, David S.; Plowright, Alleyn T.; Tornos, James A.; Ye, Tao

doi:10.1039/b308305e

Cited by 95 publications

(22 citation statements)

References 73 publications

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“…The synthesis of the C4–C16 fragment 139 commenced with the RCAER between ethyl carbonate 140 and homopropargylic alcohol 141 (Scheme 30). 73 The product was treated with palladium catalyst in the presence of Trost's chiral (+)-DPPBA ligand to afford 2,6- cis -disubstituted THP 142 , which was readily converted to aldehyde 143 through a deprotection–oxidation sequence. Leighton allylation followed by TBS protection afforded homoallyl silyl ether 144 .…”

Section: Total Synthesis Of Zampanolide and Dactylolidementioning

confidence: 99%

Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

Chen

Kingston

2014

Nat. Prod. Rep.

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Section: Total Synthesis Of Zampanolide and Dactylolidementioning

confidence: 99%

Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

Chen

Kingston

2014

Nat. Prod. Rep.

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“…[80][81][82] From a synthetic standpoint, several total syntheses have been reported. [83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98] Our approach enables the efficient access to this complex bis-pyran fragment 123 through the sequential use of our stereocomplementary ether transfercyclization reactions (Scheme 37.27).…”

Section: Formation Of 13-diol Ethersmentioning

confidence: 99%

Ether Transfer Methodology: Application to the Synthesis of Polyketide Natural Products

Stefan

Taylor

2013

Stereoselective Synthesis of Drugs and Natural Products

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This chapter comprises two major components that sequentially describe existing methods pertinent to the stereoselective formation of 1,3‐ syn ‐diol functionality and the development of a new approach to 1,3‐ syn ‐diol monoethers and diethers through electrophilic activation of homoallylic alkoxymethyl ethers. The ability to quench a key chloromethyl ether intermediate with various nucleophiles highlights the versatility of the ether transfer method. The process provides selective access to either diol‐monoethers or diethers, and it describes an opportunity to convert acyclic stereochemically rich fragments into highly functionalized pyran systems. This fundamentally new method was successfully applied to the synthesis of several complex polyketides including the synthesis of isotactic polyethers, the C7–C17 fragment of swinholide A, the C3–C17 fragment of phorboxazole A, and the neopeltolide macrolactone.

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“…49. Specific details of the synthesis and characterizations of all of the compounds researched in this article can be found in Supporting Methods, which is published as supporting information on the PNAS web site.…”

Section: Experimental Methodsmentioning

confidence: 99%

A total synthesis of estrone based on a novel cascade of radical cyclizations

Pattenden

González

McCulloch

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Two conceptually different and novel radical-mediated cascade reactions leading to a total synthesis of the steroid (؎)-estrone 1 and to a synthesis of 14-epiestrone 40 are described. Treatment of the iododienynone 23 with Bu3SnH͞2,2-azobis(isobutyronitrile) (AIBN) triggers a 13-endo-dig radical macrocyclization followed by two sequential radical transannulation reactions leading to the crystalline estrane 24 in 50% yield. The x-ray crystal structure of 24 established its trans, syn, stereochemistry. Transposition of the enone functionality in 24 next led to 38, which was then converted into 39 by reductive methylation. Deprotection of the methyl ether 39 finally gave 14-epiestone 40. When the substituted iodovinylcyclopropane 55 was treated similarly with Bu3SnH͞AIBN, the resulting radical center underwent a different sequence of cascade macrocyclization-transannulation reactions producing the trans, anti, trans estrane 56 in 12% overall yield. Oxidation of 56, using CrO 3-H2SO4 next led to the cyclopentanone 57, which, on deprotection using BBr3 gave (؎)-estrone 1. A number of alternative substituted iodopolyenynones and iodovinylcyclopropanes, i.e., 8a, 8b, 33, 49a, and 49b, underwent similar radical-mediated cascade cyclizations leading to other estranes, i.e., 21a, 21b, 35, and 50, and, in one case, to the 6,6,5,6-tetracycle 51, in variable overall yields. The structures and stereochemistries of several estranes were established by using x-ray crystal structure measurements in combination with analysis of their NMR spectroscopic data and correlation with literature precedent. Since the synthesis of the female sex hormone estrone 1 by Anner and Miescher in 1948 (1), and the syntheses of nonaromatic steroids, such as cortisone 2 and aldosterone 3 during the 1950s, a plethora of ingenious designs have been explored to synthesize members of the steroid family of natural products. Prominent among the methods that have been developed are those based on Diels-Alder reactions (2-12), transition metal-catalyzed cyclizations of enynes and triynes (13-16), and biogenetic-type electrophilic cyclizations of polyene precursors (17-21).Over the past 10 years, we (22-26) and others (27-38) have examined the scope of a variety of cascade radical-mediated processes to elaborate steroids and other polycyclic ring systems. Thus, we have already described an approach to steroids based on consecutive 6-endo-trig (ref. 39 and references therein) and sequential transannular (40) radical cyclizations from appropriate polyene selenyl ester precursors, illustrated in the conversions 4 3 5 and 6 3 7, respectively.We have now extended our studies and examined a different approach to estrone 1 and estranes, whereby the nonaromatic tricyclic B,C,D ring system is produced in a single step by radical-mediated macrocyclizations in tandem with consecutive transannulations from an appropriate ortho-disubstituted arylpolyene precursor.These approaches to estranes are captured in a retrosynthetic manner in Scheme 1. Thus, in one approach, we ha...

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Total synthesis of (+)-phorboxazole A, a potent cytostatic agent from the sponge Phorbas sp.

Cited by 95 publications

References 73 publications

Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

Ether Transfer Methodology: Application to the Synthesis of Polyketide Natural Products

A total synthesis of estrone based on a novel cascade of radical cyclizations

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