Semisynthesis and Biological Evaluation of a Novel D-Seco Docetaxel Analogue

Thoret, Sylviane; Guéritte, Françoise; Guénard, Daniel; Dubois, Joëlle

doi:10.1021/ol060531d

Cited by 21 publications

(14 citation statements)

References 25 publications

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“…40 Zhao et al prepared analogue compounds starting from isolated taxyunnansin 32. 42 Similar reactions to the rearranged 5/7/6-ring systems were also observed during acidic deprotection of silyl protecting groups, 43 as well as during deoxygenation sequences, 44 CH-activation hydroxylation methods based on radical intermediates, 45,46 and microbial transformations. 47 In addition to the A ring contraction, Appendino and coworkers observed an additional ring contraction of the B ring when treating 10-dehydro-10-deacetylbaccatin III (44) with trichloroacetic acid.…”

Section: Synthetic Efforts To Nonclassicalmentioning

confidence: 69%

“…Zhao et al prepared analogue compounds starting from isolated taxyunnansin 32 . Similar reactions to the rearranged 5/7/6-ring systems were also observed during acidic deprotection of silyl protecting groups, as well as during deoxygenation sequences, CH-activation hydroxylation methods based on radical intermediates, , and microbial transformations …”

Section: Synthetic Efforts To Nonclassical Taxanesmentioning

confidence: 88%

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The Chemistry of Nonclassical Taxane Diterpene

et al. 2021

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The taxane diterpenes are a pharmaceutically vital family of natural products, consisting of more than 550 congeners. All taxane diterpenes are isolated from slow growing evergreen shrubs (genus Taxus) commonly known as "yews" and have a history of over 50 years as potent anticancer compounds. The most prominent congener, taxol (paclitaxel = PTX), has been used in clinics for more than 25 years and is one of the top-selling anticancer drugs worldwide, with annual sales reaching 1.5 billion USD in 1999. Within the taxane diterpene family 11 different scaffolds originating from rearrangements, fragmentations, or transannular C−C bond formations of the "classical taxane core" are known. Among them, five different scaffolds alone belong to the so-called complex or cyclotaxane subfamily, their signature structural feature bearing different types and numbers of transannular C−C bonds across the classical taxane backbone. For synthetic chemists, these five scaffolds represent by far the most challenging of all and have thus evaded total synthesis as well as detailed pharmaceutical evaluationthe latter due to extremely poor sourcing from natural producers. The cousinship of complex taxanes to taxol renders them potentially interesting compounds for drug research in the fight against cancer. This Account specifically summarizes the work on nonclassical taxanes from a biosynthetic, as well as a synthetic, point and provides a synthetic perspective on complex taxanes. Special attention is given to the biosynthetic relationship of complex taxanes and their biological emergence from classical taxanes. The transannular C−C bond forming events in the biosynthesis leading to the five individual scaffolds within this subfamily are structured on the basis of the exact type and number of these specific C−C bond formations. Since functionalization of the classical taxane core in the "oxidase phase" of the biosynthesis precedes the formation of complex taxanes, and is in part prerequisite for these transannular cyclization events, a detailed discussion of these oxidations of the classical taxane backbone is provided. Synthetic efforts toward nonclassical taxanes are scarce in literature and are thus presented in a comprehensive manner for abeotaxanes and complex taxanes. The last part of this Account deals with a synthetic perspective on the synthesis of complex taxanes (cyclotaxanes) and how these most intricate scaffolds can potentially be obtained via a deconvolution strategy. This discussion involves in part unpublished results by our group and is based upon synthetic studies in the literature. The deconvolution strategy we advocate aims for selective fragmentations of the signature transannular C−C bonds of the most intricate scaffold represented by the natural product canataxpropellane, which has recently been synthesized by our group. This strategy represents the converse process of the biosynthesis of complex taxanes (e.g., transannular cyclizations) and is enabled and feasible due to our approach to the canataxpropellane sc...

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Section: Synthetic Efforts To Nonclassicalmentioning

confidence: 69%

Section: Synthetic Efforts To Nonclassical Taxanesmentioning

confidence: 88%

The Chemistry of Nonclassical Taxane Diterpene

et al. 2021

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“…The partial synthesis of a novel ring-D-seco docataxel analogue has been reported. 140 Some non-cytotoxic taxanes have been shown 141 to possess anti-tubercular activity.…”

Section: Taxanesmentioning

confidence: 99%

Diterpenoids

Hanson

2007

Nat. Prod. Rep.

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“…2). 19 All these experimental results suggest that, while not crucial for productive tubulin binding, the oxetane ring might be essential for cytotoxic activity.…”

Section: Introductionmentioning

confidence: 96%

A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids

et al. 2012

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The design, synthesis and biological evaluation of a novel C,D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.

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Semisynthesis and Biological Evaluation of a Novel D-Seco Docetaxel Analogue

Cited by 21 publications

References 25 publications

The Chemistry of Nonclassical Taxane Diterpene

The Chemistry of Nonclassical Taxane Diterpene

Diterpenoids

A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids

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