John Braun

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[person name=”John Braun” picture=”https://syborch.com/wp-content/uploads/2018/04/john-e1523885141759.jpeg” pic_link=”http:” title=”PhD Student” email=”” facebook=”” twitter=”” linkedin=”https://www.linkedin.com/in/jbraunnl” dribbble=”” linktarget=”_blank”][/person]

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Total Synthesis of Muironolide A

Oceans constitute over 90% of all liveable space on our planet, providing a habitat for an estimated 50 – 80% of all organisms^[1]. In an endeavour to map the chemical diversity, marine biologists actively explore the seabeddings for new exotic species which often synthesize a range of characteristic complex compounds.
Muironolide A is a complex natural compound isolated from the Phorbas marine sponge species. In 2009, its structure was elucidated by Molinski et al.^[2] from a 90 µg sample obtained by scuba near Muiron Island – hence the name – in Western Australia in 1993.
From the structure elucidation studies, it is found that Muironolide A belongs to the class of polyketides and interestingly encompasses an extraordinary combination of functional groups, bearing a chlorocyclopropyl moiety, trichlorocarbinol ester and a remarkably configured isoindolinone ring.
Initial biological evaluations have demonstrated that Muironolide A shows antitumor activity, however a larger sample is required for additional assays and understanding of its biological function.
Since isolation and structure elucidation followed 16 years after isolation of the marine sponge, hitherto, the Phorbas marine sponge specimen have not been found again and attention is drawn to means of synthetic reproduction. In contrast to the abilities of the fine synthetic machinery of mother Nature, to date the total synthesis of Muironolide A in the lab remains a challenge.
The retrosynthesis of Muironolide A, describes three parts: isoindolinone building block 1, trichlorocarbinol containing building block 2 and building block 3 consisting of a chlorinated cyclopropyl moiety.

Only a small number of articles are published^[3] on synthetic routes towards Muironolide A and they are mainly focused on the synthesis of the hexahydro-1H-isoindolinone moiety, characterized by presence of a chiral quaternary center and the thermodynamically unfavoured regioselectivity of the olefin.
In my PhD project, novel synthetic pathways towards the synthesis of the isoindolinone 1 and chloro-cyclopropyl building block 3 of Muironolide A will be explored, ultimately leading to the total synthesis of Muironolide A.

[1] Secretariat of the Convention on Biological Diversity. (2012). Marine Biodiversity—One Ocean, Many Worlds of Life (p. 77). Montreal.
[2] D. S. Dalisay, B. I. Morinaka, C. K. Skepper, T. F. Molinski, J. Am. Chem. Soc. 2009, 131, 7552–7553.
[3] a) B. Flores, T. F. Molinski, Org. Lett. 2011, 13, 3932–5; b) Q. Xiao, K. Young, A. Zakarian, Org. Lett. 2013, 15, 3314–3317.

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