Total Synthesis of (+)-13-Deoxytedanolide

Julian, Lisa D.; Newcom, Jason S.; Roush, William

doi:10.1021/ja050729d

Cited by 49 publications

(37 citation statements)

References 29 publications

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“…Based on this analysis Roush's synthesis used the (15R)-configuration for the synthesis of 13-deoxytedanolide (2). [10] Unfortunately, the R configuration in combination with the presence of a carbonyl group at C5 led to the formation of a stable hemiketal that inhibited oxidation of the hydroxyl group. Based on experiences in our synthesis of callystatin [17] we realized that the inherent stereochemistry of methyl ketone 8 would be a substitute for a chiral auxiliary that would override the stereochemical preferences of the aldehyde 9.…”

Section: Synthesis Of Aldehydementioning

confidence: 99%

“…For this conversion we followed the protocol established by Roush for the synthesis of 13-deoxytedanolide (2). [10] 3 HF·Et 3 N was described to be only slightly acidic and a combination of this reagent and additional triethylamine proved suitable for deprotection of lactone 6. The deprotection followed a statistical loss of TBS groups and after 4 d one defined compound with only one remaining TBS group was isolated together with 32 % of completely deprotected lactone 49.…”

Section: Synthesis Of Aldehydementioning

confidence: 99%

“…Very recently, their concept resulted in a total synthesis for tedanolide ( 1 ) as well 9. Short after the first synthesis of 13‐deoxytedanolide ( 2 ) had been completed a second total synthesis of 2 by the Roush group was published 10. Here we describe the synthetic details that led to our total synthesis of tedanolide ( 1 ) 11.…”

Section: Introductionmentioning

confidence: 98%

“…[9] Short after the first synthesis of 13-deoxytedanolide (2) had been completed a second total synthesis of 2 by the Roush group was published. [10] Here we describe the synthetic details that led to our total synthesis of tedanolide (1). [11] The key features are an aldol coupling to set up the carbon backbone and a final stage epoxidation.…”

Section: Introductionmentioning

confidence: 99%

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The Total Synthesis of (+)‐Tedanolide—A Macrocyclic Polyketide from Marine Sponge Tedania ignis

Ehrlich

Hassfeld

Eggert

et al. 2008

Chemistry A European J

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Tedanolide, which was isolated by Schmitz in 1984 from the marine sponge Tedania ignis, is a highly cytotoxic macrolide leading to strong growth inhibition of P338 tumor cells in bioassays. A unique structural feature of the known tedanolides is the primary hydroxyl group incorporated in the macrolactone. This unusual motif for macrolactones originated from PKS biosynthesis might arise through lactonizations others than those derived by the thioesterase reaction. First experimental data that support this hypothesis and reflect the inherent preference of PKS-induced macrolactonization were obtained during this synthesis. The inherent preference for the formation of a 14-membered macrocyclization is discussed together with the pivotal steps in the synthesis.

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Section: Synthesis Of Aldehydementioning

confidence: 99%

Section: Synthesis Of Aldehydementioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Total Synthesis of (+)‐Tedanolide—A Macrocyclic Polyketide from Marine Sponge Tedania ignis

Ehrlich

Hassfeld

Eggert

et al. 2008

Chemistry A European J

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“…In the course of our program to provide synthetic access to biologically active natural products [1] we choset he tedanolides [2] as promising targets.W ithin this familyo fs econdary metabolites tedanolide C(1) [3] (Figure 1) attractedour attention due to its unusual polyoxygenated structure exhibiting atertiary alcohol. Additionally,t he ongoing discussion about its configuration prompted us to focus on the Kiyooka aldol reaction with ketene acetal 7.I ng eneral,t ertiary alcohols are important structuralm otifs in the synthesis of natural products as well as challenging synthetict argets.…”

mentioning

confidence: 99%

Polyoxygenated Tertiary Alcohols: A Kiyooka Approach

Lücke

Kalesse

2019

Chemistry A European J

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A Kiyooka aldol approach for the stereoselective synthesis of tertiary alcohols is presented. This approach allows for the incorporation of different substituents at all three remaining positions at the chiral center bearing the tertiary alcohol. To demonstrate the validity of this approach different chiral alcohols were depicted and the relationship of double bond geometry of the ketene acetal and the diastereoselectivity was established.

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The Barton‐McCombie Reaction

2012

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Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site‐specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon‐centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C‐O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high‐yielding way to realize this sequence was first described by Barton McCombie using the free‐radical chain reaction of O ‐thioacyl derivatives of secondary alcohols with tri‐ n ‐butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products.

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Total Synthesis of (+)-13-Deoxytedanolide

Cited by 49 publications

References 29 publications

The Total Synthesis of (+)‐Tedanolide—A Macrocyclic Polyketide from Marine Sponge Tedania ignis

The Total Synthesis of (+)‐Tedanolide—A Macrocyclic Polyketide from Marine Sponge Tedania ignis

Polyoxygenated Tertiary Alcohols: A Kiyooka Approach

The Barton‐McCombie Reaction

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