Synthesis of the QRSTU Domain of Maitotoxin and Its 85-<i>epi</i>- and 86-<i>epi</i>-Diastereoisomers

Nicolaou, K. C.; Gelin, Christine F.; Seo, Jae Hong; Huang, Zhihong; Umezawa, Taiki

doi:10.1021/ja103708j

Cited by 35 publications

(26 citation statements)

References 61 publications

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“…Assignment of these chemical shifts allowed us to compare them to those corresponding to the same region of maitotoxin3d, an exercise that has previously served as a means for supporting the assigned structure of the natural product 3–5,8–12,13d,e,g. The chemical shifts (δ, ppm) for synthetic fragment 6 , those for the same carbons (C 119 to C 135 and C 160 to C 162 ) of maitotoxin ( 1 )3d, and their differences (Δδ, ppm) are given in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of the C′D′E′F′ Domain of Maitotoxin

et al. 2010

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A devised biomimetic strategy toward the C′D′E′F′ domain (6) of maitotoxin (1) led to hydroxy triepoxide 8 as a postulated polyepoxide precursor. However, all attempts to induce the desired cascade to form the targeted compound through a zip-type reaction under neutral or acidic conditions failed, prompting adoption of a linear stepwise approach to 6. The successful synthetic strategy for the synthesis of the C′D′E′F′ domain of maitotoxin commenced from furfuryl alcohol (11), proceeded through F′ ring building block 15, and involved two regio-and stereoselective intramolecular hydroxy epoxide openings and a stereoselective SmI 2 -mediated ring closure to forge rings C′, E′, and D′, respectively. 13 C NMR spectroscopic analysis of the synthesized domain (6) and comparisons with previous results confirmed the original structural assignment of this region of maitotoxin. X-Ray crystallographic analysis of 6 provided unambiguous proof of its structure.

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Section: Resultsmentioning

confidence: 99%

Synthesis of the C′D′E′F′ Domain of Maitotoxin

et al. 2010

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“…With this domain ( 7 ) of maitotoxin now synthesized, a set of six large domains (i.e. 2–7 , Figure 1) of this neurotoxin have been completed 1,5–8. With appropriate modifications, the developed routes to these fragments can, in principle, deliver suitable fragments, whose coupling and further elaboration may lead to even larger domains of the natural product.…”

Section: Resultsmentioning

confidence: 99%

“…1) of this molecule and confirm its original stereochemical assignment3 through 13 C NMR comparison with the natural product. With this accomplishment, all the major domains of maitotoxin ( 1 ) have now been synthesized, including fragments 2 5, 3 6, 4 7, 5 8, 6 1 and 7 (present work) (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the WXYZA′ Domain of Maitotoxin

2010

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A synthesis of the WXYZA′ domain (7) of the marine neurotoxin maitotoxin (1) is reported. The convergent synthetic strategy involves construction of key building blocks 11 and 12, their coupling, and the elaboration of the resulting ester (10) to the target molecule through a ringclosing metathesis and a hydroxy dithioketal cyclization as the key steps. For the construction of fragment 11, the Noyori reduction/Achmatowicz rearrangement and hydroxy epoxide opening technologies were applied [starting from furfuryl alcohol (13)], whereas for the synthesis of fragment 12, a carbohydrate-based approach was adopted [starting from 2-deoxy-D-ribose (14)]. The synthesized WXYZA′ domain (7) of maitotoxin (1) exhibited the expected 13 C NMR chemical shifts, supporting the originally assigned structure of the corresponding region of the natural product.

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“…[46] The main challenge presented by this pentacyclic system derived from the five rather congested methyl groups residing on its periphery. The designed convergent synthetic strategy ( 103 + 104 → 105 → 106 → 107 → 108 → 109 , Scheme 16a) called upon an intramolecular ester olefin ring closure [29–33] ( 105 → 106 ) and a cyclic O,S -acetal formation/methylation [15,16] ( 107 → 108 ) to cast the final two rings of the molecule.…”

Section: Synthesis Of Maitotoxin Domainsmentioning

confidence: 99%

Maitotoxin: An Inspiration for Synthesis

Nicolaou

Aversa

2011

Israel Journal of Chemistry

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Maitotoxin holds a special place in the annals of natural products chemistry as the largest and most toxic secondary metabolite known to date. Its fascinating, ladder-like, polyether molecular structure and diverse spectrum of biological activities elicited keen interest from chemists and biologists who recognized its uniqueness and potential as a probe and inspiration for research in chemistry and biology. Synthetic studies in the area benefited from methodologies and strategies that were developed as part of chemical synthesis programs directed toward the total synthesis of some of the less complex members of the polyether marine biotoxin class, of which maitotoxin is the flagship. This account focuses on progress made in the authors’ laboratories in the synthesis of large maitotoxin domains with emphasis on methodology development, strategy design, and structural comparisons of the synthesized molecules with the corresponding regions of the natural product. The article concludes with an overview of maitotoxin’s biological profile and future perspectives.

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Synthesis of the QRSTU Domain of Maitotoxin and Its 85-epi- and 86-epi-Diastereoisomers

Cited by 35 publications

References 61 publications

Synthesis of the C′D′E′F′ Domain of Maitotoxin

Synthesis of the C′D′E′F′ Domain of Maitotoxin

Synthesis of the WXYZA′ Domain of Maitotoxin

Maitotoxin: An Inspiration for Synthesis

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