Isolation and characterization of a new 12-membered macrolide FD-895.

Seki-Asano, Mitsuko; Okazaki, Takao; Yamagishi, Masaaki; Sakai, Noriyoshi; Takayama, Yoko; Hanada, Kazunori; Morimoto, Shigeo; Takatsuki, Akira; Mizoue, Kazutoshi

doi:10.7164/antibiotics.47.1395

Cited by 43 publications

(56 citation statements)

References 16 publications

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“…Access to splice modulators (SPLMs) has evolved from the early stages of natural product isolation[3––5] to the current state of medicinal chemistry optimization and high-fidelity total synthesis. [6––17] To date, the most established set of SPLMs share a common mode of action (MOA), targeting the SF3b multiprotein component within the U2 small nuclear ribonucleoprotein (snRNP) of the spliceosome.…”

Section: The Chemistry Of Splice Modulationmentioning

confidence: 99%

A Challenging Pie to Splice: Drugging the Spliceosome

et al. 2017

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Since its discovery in 1977, the study of alternative RNA splicing has revealed a plethora of mechanisms that had never before been documented in nature. Understanding these transitions and their outcome at the level of the cell and organism has become one of the great frontiers of modern chemical biology. Until 2007, this field remained in the hands of RNA biologists. However, the recent identification of natural product and synthetic modulators of RNA splicing has opened new access to this field, allowing for the first time a chemical-based interrogation of RNA splicing processes. Simultaneously, we have begun to understand the vital importance of splicing in disease, which offers a new platform for molecular discovery and therapy. As with many natural systems, gaining clear mechanistic detail at the molecular level is key towards understanding the operation of any biological machine. This minireview presents recent lessons learned in this emerging field of RNA splicing chemistry and chemical biology.

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Section: The Chemistry Of Splice Modulationmentioning

confidence: 99%

A Challenging Pie to Splice: Drugging the Spliceosome

et al. 2017

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“…1) introduced a family of 12–membered macrolides identified with potent cytostatic activity during hypoxia response. 1 A decade later, studies at Eisai Co. Ltd. led to the isolation of related macrolides including pladienolides B ( 2a ) and D ( 2b ). 2 In 2007, the complete structure of 2b (Fig.…”

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confidence: 99%

Structure of FD-895 Revealed through Total Synthesis

Villa¹,

Mandel²,

Jones³

et al. 2012

Org. Lett.

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The total synthesis of FD–895 was completed through a strategy that featured the use of a tandem esterification ring–closing metathesis (RCM) process to construct the 12–membered macrolide and a modified Stille coupling to append the side chain. These studies combined with detailed analysis of all four possible C16–C17 stereoisomers, was used to confirm the structure of FD–895 and identify an analog with an enhanced sub-nanomolar bioactivity.

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“…Identified in 1994, 11 FD-895 was the first member of a large family of polyketides isolated from related strains of Streptomyces platensis, which includes pladienolide-B (PLAD-B) and pladienolide-D (PLAD-D) (Online Supplementary Figure S1). 12 PLAD-B targets the splicing factor subunit SF3b and this interaction is postulated to be responsible for its mechanism of antitumor activity.…”

Section: Introductionmentioning

confidence: 99%