Total Synthesis of Apoptolidin

Wehlan, Hermut; Dauber, Mario; Fernaud, M. Teresa Mujica; Schuppan, Julia; Mahrwald, Rainer; Ziemer, Burkhard; Garcia, M.‐Elisa Juarez; Koert, Ulrich

doi:10.1002/anie.200460172

Cited by 57 publications

(10 citation statements)

References 28 publications

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“…Syntheses of apoptolidinone A, the aglycone of 1, were reported by the groups of Sulikowsky [143], Crimmins [144], Nicolaou [138][139][140], and Koert [141,142]. In addition, several studies on the synthesis of fragments of apoptolidinones have been reported [137,[145][146][147][148][149][150][151][152][153][154][155].…”

Section: Methodsmentioning

confidence: 97%

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Use of sultines in the asymmetric synthesis of polypropionate antibiotics

Vogel

Turks

Bouchez

et al. 2008

Pure and Applied Chemistry

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At low temperature and in the presence of an acid catalyst, SO 2 adds to 1,3-dienes equilibrating with the corresponding 3,6-dihydro-1,2-oxathiin-2-oxides (sultines). These compounds are unstable above -60°C and equilibrate with the more stable 2,5-dihydrothiophene 1,1-dioxides (sulfolenes). The hetero-Diels-Alder additions of SO 2 are suprafacial and follow the Alder endo rule. The sultines derived from 1-oxy-substituted and 1,3-dioxydisubstituted 1,3-dienes cannot be observed at -100°C but are believed to be formed faster than the corresponding sulfolenes. In the presence of acid catalysts, the 6-oxy-substituted sultines equilibrate with zwitterionic species that react with electron-rich alkenes such as enoxysilanes and allylsilanes, generating β,γ-unsaturated silyl sulfinates that can be desilylated and desulfinylated to generate polypropionate fragments containing up to three contiguous stereogenic centers and an (E)-alkene unit. Alternatively, the silyl sulfinates can be reacted with electrophiles to generate polyfunctional sulfones (one-pot, four-component synthesis of sulfones), or oxidized into sulfonyl chlorides and reacted with amines, then realizing a one-pot, four-component synthesis of polyfunctional sulfonamides. Using enantiomerically enriched dienes such as 1-[(R)-or 1-(S)-phenylethyloxy]-2-methyl-(E,E)-penta-1,3-dien-3-yl isobutyrate, derived from inexpensive (R)-or (S)-1-phenylethanol, enantiomerically enriched stereotriads are obtained in one-pot operations. The latter are ready for further chain elongation. This has permitted the development of expeditious total asymmetric syntheses of important natural products of biological interest such as the baconipyrones, rifamycin S, and apoptolidin A.

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Section: Methodsmentioning

confidence: 97%

“…Successful total synthesis of 1 has been achieved by the groups of Nicolaou [138][139][140] and Koert [141,142]. Syntheses of apoptolidinone A, the aglycone of 1, were reported by the groups of Sulikowsky [143], Crimmins [144], Nicolaou [138][139][140], and Koert [141,142].…”

Section: Methodsmentioning

confidence: 99%

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

Vogel

Turks

Bouchez

et al. 2008

Pure and Applied Chemistry

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“…Total synthesis of apoptolidin (90), a metabolite of Nocardiopsis sp. which displayed potent antitumor activities, was accomplished by several research groups via a similar glycosyl sulfoxide method (Scheme 21) [123][124][125]. In Nicolaou's synthesis, coupling of the complex alcohol 92 with sulfoxide 91 was performed in the presence of Tf 2 O (2.5 equiv.)…”

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confidence: 99%

O-Glycosylation methods in the total synthesis of complex natural glycosides

2015

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The total syntheses of 33 complex natural O-glycosides, such as the glycosides of macrocyclic lactones/lactams, enediynes, angucyclines, and anthracyclines, are highlighted, with a major focus being placed on the O-glycosylation reactions which connect the saccharides and the aglycones. These successful O-glycosylation reactions employ such donors as glycosyl bromides, fluorides, iodides, trichloroacetimidates, N-phenyl trifluoroacetimidates, thioglycosides, sulfoxides, heteroaryl thioglycosides, 1-hydroxyl sugars, 1-O-acetates, and ortho-alkynylbenzoates. Each synthesis is depicted starting from the O-glycosylation of the aglycone (or its precursor); the glycosylation conditions and outcomes (yields and stereoselectivities) are discussed, and the subsequent transformations toward the final target, including the elongation of the glycan, the elaboration of the aglycone, and the protecting group manipulations are also given in detail.

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“…[5] In 2001 Koert reported the synthesis of apoptolidinone [6] and later the same year Nicolaou described the total synthesis of apoptolidin. [7] Three years later the Koert group described the total synthesis of apoptolidin [8] and our group reported the second synthesis of the aglycon apoptolidinone. [9] The first total synthesis of apoptolidin reported by the Nicolaou group [7] and other recent work [10] demonstrated apoptolidin to be a rather labile compound that undergoes a base-induced acyl migration from a hydroxy group located at C19 to the neighboring C20 hydroxy group to produce isoapoptolidin (3), a compound possessing diminished activity against mitochondrial F 0 F 1 -ATPase.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Synthesis of Apoptolidin: Progress on the Stereocontrolled Assembly of the Pseudo Aglycone of Apoptolidin

Wu¹,

Liu²,

Jin³

et al. 2005

Eur J Org Chem

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Progress on a stereocontrolled total synthesis of the pseudo aglycone of apoptolidin (2) starting from (S)‐epichlorohydrin is reported. The lower C(12)–C(28) fragment (4) was derived by consecutive stereoselective aldol reactions and extended using a Suzuki cross‐coupling reaction. Studies on glycoyslation of the C9 hydroxy group are also described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Total Synthesis of Apoptolidin

Abstract: A ring‐size‐selective macrolactonization and the early introduction of the saccharide portions are the main features of a total synthesis of the 20‐membered macrolide apoptolidin (see formula), which induces apoptosis in rat glia cells transformed with oncogenes.

Cited by 57 publications

References 28 publications

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

O-Glycosylation methods in the total synthesis of complex natural glycosides

Studies on the Synthesis of Apoptolidin: Progress on the Stereocontrolled Assembly of the Pseudo Aglycone of Apoptolidin

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