Concise route to defined stereoisomers of the hydroxy acid of the chondramides

Schmauder, Anke; Müller, S.; Maier, Martin E.

doi:10.1016/j.tet.2008.04.109

Cited by 37 publications

(20 citation statements)

References 40 publications

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“…These studies commenced with the known vinylogous Mukaiyama aldol reaction of 33 and acetaldehyde to provide the corresponding aldol adduct (93 %y ield, > 20:1 d.r.). [21] Protection of this adduct (TBSCl, DMAP,I mH) followed by reductive removal of the auxiliary (NaBH 4 ,8 4% yield, 2s teps) and Parikh-Doering oxidation of the resultant alcohol provided aldehyde 34.A ldehyde 34 was then subjected to the Evans syn-selective aldol reaction [22] with ac hiral oxazolidinone 35 to provide the correspondinga ldol adduct (> 20:1 d.r.) that was converted to silyl ether 36 (79 %y ield, 2s teps).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Lactimidomycin and Its Analogues

Larsen

Sun

Lachacz

et al. 2015

Chemistry A European J

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The studies culminating in the total synthesis of the glutarimide-containing eukaryote translation elongation inhibitor lactimidomycin are described. The optimized synthetic route features a Zn(II)-mediated intramolecular Horner-Wadsworth-Emmons (HWE) reaction resulting in a highly stereoselective formation of the strained 12-membered macrolactone of lactimidomycin on a 423 mg scale. The presence of the E,Z-diene functionality was found to be key for effective macrocyclizations as a complete removal of these unsaturation units resulted in exclusive formation of the dimer rather than monocyclic enoate. The synthetic route features a late-stage installation of the glutarimide functionality via an asymmetric catalytic Mukaiyama aldol reaction, which allows for a quick generation of lactimidomycin homolog 55 containing two additional carbons in the glutarimide side chain. Similar to lactimidomycin, this analog was found to possess cytotoxicity against MDA-MB-231 breast cancer cells (GI50 =1-3 μM) using in vitro 2D and 3D assays. Although lactimidomycin was found to be the most potent compound in terms of anticancer activity, 55 as well as truncated analogues 50-52 lacking the glutarimide side-chain were found to be significantly less toxic against human mammary epithelial cells.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Lactimidomycin and Its Analogues

Larsen

Sun

Lachacz

et al. 2015

Chemistry A European J

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“…70 In our own work related to the chondramides we initially developed a concise synthesis of the ω-hydroxy acid based on a vinylogous aldol reaction and an asymmetric alkylation. 71 Thereafter, we achieved a total synthesis of chondramide A. 72 Unlike chondramide C which contains a β-tyrosine, chondramide A features a 2-methoxy-β-tyrosine.…”

Section: Chondramide a Analoguesmentioning

confidence: 99%

Design and synthesis of analogues of natural products

Maier

2015

Org. Biomol. Chem.

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138

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In this article strategies for the design and synthesis of natural product analogues are summarized and illustrated with some selected examples. Proven strategies include diverted total synthesis (DTS), function-oriented synthesis (FOS), biology-oriented synthesis (BIOS), complexity to diversity (CtD), hybrid molecules, and biosynthesis inspired synthesis. The latter includes mutasynthesis, the synthesis of natural products encoded by silent genes, and propionate scanning. Most of the examples from our group fall in the quite general concept of DTS. Thus, in case an efficient strategy to a natural product is at hand, modifications are possible at almost any stage of a synthesis. However, even for compounds of moderate complexity, organic synthesis remains a bottle neck. Unless some method for predicting the biological activity of a designed molecule becomes available, the design and synthesis of natural product analogues will remain what it is now, namely it will largely rely on trial and error.

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“…11,12 Retrosynthetically, chondramide A was constructed from two fragments, vhydroxyester 31 and the peptide fragment 35 (Figure 2.4). A Yamaguchi esterification should then lead to the fully functionalised, linear precursor 36.…”

Section: Total Synthesis Of Chondramide a By Maiermentioning

confidence: 99%