The Structures of Amphidinolide B Isomers: Strongly Cytotoxic Macrolides Produced by a Free-Swimming Dinoflagellate, Amphidinium sp

Bauer, Ines; Maranda, Lucie; Shimizu, Yuzuru; Peterson, Russell W.; Cornell, Laurie; Steiner, Jorge Rios; Clardy, Jon

doi:10.1021/ja00085a071

Cited by 77 publications

(43 citation statements)

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“…5). One example is the macrolide, amphidinolide B (7) (Bauer et al, 1994), which showed a mean IC 50 of 0.2 mM in the BMS ODCA panel, minimal cell line selectivity and no activity against i.p./i.p. P388.…”

Section: Mass Scale Cultivation and Isolation Of Metabolitesmentioning

confidence: 99%

New Anticancer Drugs from Cultured and Collected Marine Organisms

Fenical

Jensen

Kauffman

et al. 2003

Pharmaceutical Biology

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Section: Mass Scale Cultivation and Isolation Of Metabolitesmentioning

confidence: 99%

New Anticancer Drugs from Cultured and Collected Marine Organisms

Fenical

Jensen

Kauffman

et al. 2003

Pharmaceutical Biology

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“…18 Acetylation of 17 proved to be nontrivial. Powerful acetylation protocols such as Ac 2 O/catalytic TMSOTf 19 and Ac 2 O/catalytic Sc(OTf) 3 20 were not successful. However, acetylation was achieved using Ac 2 O/4-pyrrolidinopyridine in reproducible, albeit 40-50% yield.…”

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confidence: 99%

Stereoselective Assembly of a 1,3-Diene via Coupling between an Allenic Acetate and a (B)-Alkylborane: Synthetic Studies on Amphidinolide B1

2005

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The preparation of three fragments for the total synthesis of amphidinolide B1 has been described. The C16 stereochemistry was set by asymmetric allylic alkylation. C21 and C25 stereogenic centers were set by an enantioselective/diastereoselective double allylation reaction. The C9 configuration was set by an asymmetric heteroene reaction. A differentially substituted stereodefined 1,3-diene iodide was synthesized by iodide-mediated S N 2′ reaction. A novel stereoselective method to assemble a 1,3-diene by coupling an allenic acetate and (B)-alkylborane is also reported.Amphidinolide B1 1, a polyketide-based 26-membered macrolide, was isolated from a culture of the symbiotic marine dinoflagellate Amphidinium sp. (strain Y-5) in 1987 by Kobayashi et al. 1 Compound 1 exhibits potent and selective cytotoxicity against L1210 murine leukemia and KB human epidermoid carcinoma cell lines in vitro (IC 50 0.00014 and 0.0042 µg/mL, respectively). 1,2 The relative stereochemistry of the nine stereogenic centers in amphidinolide B1 was determined by X-ray crystallographic analysis, 3 and the absolute stereochemistry was assigned on the basis of the chemical synthesis of the C22-C26 segment. 4 Due to its potent cytotoxic activity and topological complexities, amphidinolide B1 1 has attracted the attention of synthetic chemists for over 15 years. 5 There have been several efforts toward the total synthesis of this natural product; however, no completed total synthesis has yet been reported. Both Pattenden et al. and Kobayashi et al. reported elegant approaches toward 1. 5d,6 Nishiyama, Chakraborty, Myles, Lee, and Carter have also reported partial syntheses toward 1. 7 In our chemical biology program, we are interested in developing natural products as biological probes to identify novel proteins for therapeutic intervention (target validation) and the exploration of cell biology (chemical genetics). As amphidinolide B1 1 is a highly potent anticancer agent, it can be useful as a tool for understanding more about cancer biology. As a result of our interest in the biology of this molecule, we initiated a program directed toward completing the total synthesis of amphidinolide B1 1.Our proposed synthetic route to 1 is based on a highly convergent disconnection of the 26-membered macrolide ring: Mitsunobu-type esterification, 8 Suzuki-Miyaura coupling 9 craig.crews@yale.edu. Supporting Information Available: Experimental procedures, characterization data, and stereochemical proofs. This material is available free of charge via the Internet at http://pubs.acs.org. between C12 and C13, aldol reaction 10 between C18 and C19, and Horner-WadsworthEmmons reaction across C2-C3 (Scheme 1). NIH Public AccessUse of a 1,3-diene iodide system such as fragment 3 as a substrate for Suzuki-Miyaura coupling is unprecedented in the literature. 11 We hope to attain a high level of stereo-induction to install the C11 stereogenic center by proper choice of hydroborating agent and fine-tuning of the protecting groups of the C8 and C9 hydrox...

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“…In the last decade, some species belonging to this group have gained attention and are being used as a 'model' organism for research into dinoflagellate genetics, polyketide production (including cytotoxins and ichthyotoxins), and photosynthesis (Kobayashi et al 1991;Satake et al 1991;Bauer et al 1994Bauer et al , 1995Paul et al 1996;Houdai et al 2001;Damjanovic et al 2000;Kleima-Foske et al 2000a, b, Ten Lohuis andMiller 1998;Kubota et al 2006). Even though Amphidinium forms a dominant phytobenthos and known to be a nice prey for protistan grazers (Jeong et al 2001), its ecological significance in their role as primary producer, biogeochemical cycling, and food-web dynamics in the benthic system is largely unknown.…”

Section: Identification and Distribution Of Amphidiniummentioning

confidence: 99%

Benthic dinoflagellate blooms in tropical intertidal rock pools: elucidation of photoprotection mechanisms

et al. 2017

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LT-RPs. The observed differences can thus be attributed to the microalgal composition differences and to differences in experienced irradiance of these communities. Dynamic photoinhibition was more prominent in LT-RPs followed by MT-RPs and HT-RPs. The high accumulation of photoprotective pigments in HT-RPs (due to prolong exposure to solar radiation) could be the reason for the differences. The presence of reduced de-epoxidation state and the mid-day depression in F v /F m coupled with elevated σ PSII confirmed dominance of NPQ of reaction centres in HT-RPs compared to other pools. This study concludes that RP planktonic microalgae are eurythermal, euryhaline, and euryphotic. Concerned with increasing harmful algal bloom events further studies on diverse aspects of RP microalgae (including chemical mediated interactions) needs attention.

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The Structures of Amphidinolide B Isomers: Strongly Cytotoxic Macrolides Produced by a Free-Swimming Dinoflagellate, Amphidinium sp

Cited by 77 publications

References 0 publications

New Anticancer Drugs from Cultured and Collected Marine Organisms

New Anticancer Drugs from Cultured and Collected Marine Organisms

Stereoselective Assembly of a 1,3-Diene via Coupling between an Allenic Acetate and a (B)-Alkylborane: Synthetic Studies on Amphidinolide B1

Benthic dinoflagellate blooms in tropical intertidal rock pools: elucidation of photoprotection mechanisms

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