Synthesis of an Acyclic C1–C11 Fragment of Peloruside B

Zang, Qin; Gulab, Shivali A.; Stocker, Bridget L.; Baars, Sylvia M.; Hoberg, John O.

doi:10.1002/ejoc.201100053

Cited by 5 publications

(2 citation statements)

References 40 publications

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“…11 A synthesis of peloruside B and fragments pertaining to the peloruside skeleton have also been reported. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] The preparation of analogues of peloruside A has attracted interest for several reasons. Firstly, structurally simplified variants could facilitate the development of this important preclinical anticancer lead.…”

Section: Introductionmentioning

confidence: 99%

Synthetic, semisynthetic and natural analogues of peloruside A

Brackovic

Harvey

2015

Chem. Commun.

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Peloruside A is a macrocyclic natural product from a New Zealand marine sponge Mycale hentscheli. It has attracted significant attention in the synthetic chemistry, cellular and structural biology communities due to its complex structure and potent anticancer activity. Several natural congeners have since been isolated and synthetic analogues have been prepared. This review describes in detail the published syntheses of peloruside analogues and discusses the structure-activity relationships available to date.

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Section: Introductionmentioning

confidence: 99%

Synthetic, semisynthetic and natural analogues of peloruside A

Brackovic

Harvey

2015

Chem. Commun.

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“…Next, we decided to exchange the nucleophile, 2-allyl-1,3-dithiane, for the unsubstituted, 1,3-dithiane, as there were more literature examples of the reaction of various iodides and bromides with 1,3dithiane itself than with substituted dithianes. 156,160,170 If this reaction was successful the resulting product could be allylated in the next step.…”

Section: Dithiane Couplingmentioning

confidence: 99%

Developing a scalable synthesis of Peloruside A

Brackovic¹

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<p>Peloruside A (PelA, 1) is a marine natural product isolated from a sponge Mycale hentscheli found in Pelorus Sound, New Zealand. It is a microtubule-stabilising agent, active against various cancerous cell lines at nanomolar concentrations and offers several advantages over the current drugs on the market due to its unique mode of microtubule stabilisation, its potency and its activity in multidrug resistant cells. Since large-scale isolation of the compound from the sponge is unsustainable and an attempt to grow the sponge failed due to a sea-slug infestation, devising an efficient synthesis of peloruside A that will be able to deliver larger quantities of this compound is essential in order to conduct further studies and enable the eventual manufacture of the drug. Peloruside A is also a very interesting synthetic target as a macrolide with ten stereogenic centres, an internal pyran ring and a trisubstituted Z-double bond. Our synthetic strategy combines elements from previous total and partial syntheses with novel elements with an aim to make the synthesis more efficient. The synthesis of the side-chain fragment (C12–C20) was based on Evans' methodology1 which was also utilised to couple this fragment with the C8–C11 fragments. It was envisioned to evaluate two different end-game strategies, and to this end it was necessary to synthesise two different versions of the C8–C11 fragment. However, the synthesis of the C1–C7 fragments proved to be quite challenging and required a lot of alterations to the synthetic plan and the protecting group strategy. Various routes based on previous syntheses by Ghosh, Jacobsen and Taylor were explored.2–4 Eventually, the key intermediate was synthesised using a modified Taylor methodology. Our future work will focus on optimising and establishing fragment coupling methodologies and evaluating the two end-game approaches: macrolactonisation and a ring-closing metathesis.</p>

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