Studies Directed Towards the Synthesis of Bryostatin: A Stereoselective Synthesis of the C7–C16 Fragment

Yadav, J. S.; Subramanian, Aravind; Gundluru, Mahesh Kumar; Reddy, B. V. Subba

doi:10.1055/s-0032-1317164

Cited by 9 publications

(2 citation statements)

References 2 publications

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“…In 2012, Yadav and co-workers reported a different synthetic route to the B-ring (Scheme 3). 16 Base-catalyzed ring opening of lactone 16 led to oxy-Michael precursor 17, which was further transformed into tertahydropyran 18 in 87% overall yield. Subsequent formation of the exocyclic Z-enoate was achieved by dehydrating the tertiary hydroxy group in 18 to afford 19 in 67% yield.…”

Section: Cyclization/hwe Approachmentioning

confidence: 99%

Recent efforts to construct the B-ring of bryostatins

Song

2013

Chem. Commun.

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Among macrocyclic natural products, bryostatins have excellent bioactivities and unique structures that make them highly attractive to synthetic chemists. Particularly challenging for the total synthesis of bryostatins is the B-ring, which features a cis-tetrahydropyran containing a geometrically defined exocyclic Z-methyl enoate. Synthetic chemists have recently displayed great prowess in their efforts to construct this ring, and here we summarize the progress towards this goal.

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Section: Cyclization/hwe Approachmentioning

confidence: 99%

Recent efforts to construct the B-ring of bryostatins

Song

2013

Chem. Commun.

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“…After the methylation, α-hydroxylation using Davis' methodology 82,83 should give the C8 hydroxyl (229). The PMB group at O15 and the auxiliary would then be removed to give the seco-acid (230). Macrolactonisation using the Yamaguchi protocol 57,58 and global deprotection should give peloruside A after 21 steps (lls).…”

Section: Future Workmentioning

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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Cross‐Metathesis

O’Leary¹,

O’Neil²

2015

Handbook of Metathesis

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Studies Directed Towards the Synthesis of Bryostatin: A Stereoselective Synthesis of the C7–C16 Fragment

Cited by 9 publications

References 2 publications

Recent efforts to construct the B-ring of bryostatins

Recent efforts to construct the B-ring of bryostatins

Developing a scalable synthesis of Peloruside A

Cross‐Metathesis

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