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MESO-JBIR-102

Development of the aza-Prins reaction; synthesis and biological evaluation of JBIR-102

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

MESO-JBIR-102 project word cloud

Explore the words cloud of the MESO-JBIR-102 project. It provides you a very rough idea of what is the project "MESO-JBIR-102" about.

centre first isolated symptoms possesses found market small 12 2012 group original radiotherapy see starting lt lung prepare approx cancers months little had crucially consequently optimise 35 specialist deaths synthesis exposure good place point big 1 cell discovery partial aza period pleurectomy human aggressive jbir life lines cure limited disease architecture reported 20th annum compounds exhibit rl78 silyl pleural expectancy reaction biology architectures saccharopolyspora 2300 prepared until 18 termed mesothelioma latency natural continue rapid appear drugs drug frequently malignant fatal structural 102 asbestos chemotherapeutic century always bicycles cancer treatments prins surprise sp alkaloids

Project "MESO-JBIR-102" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITY OF GREENWICH Organization address address: Old Royal Naval College, Park Row, Greenwich city: LONDON postcode: SE10 9LS website: www.gre.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	United Kingdom [UK]
Project website	https://www.gre.ac.uk/people/rep/faculty-of-engineering-and-science/adrian-dobbs
Total cost	195˙454 €
EC max contribution	195˙454 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2015
Funding Scheme	MSCA-IF-EF-ST
Starting year	2016
Duration (year-month-day)	from 2016-07-01 to 2018-10-16

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITY OF GREENWICH UNIVERSITY OF GREENWICH Organization address address: Old Royal Naval College, Park Row, Greenwich city: LONDON postcode: SE10 9LS website: www.gre.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (LONDON)	coordinator	195˙454.00

Map

Project objective

Human malignant pleural mesothelioma is an aggressive (fatal) lung cancer which is always associated with previous asbestos exposure. Typically symptoms do not appear until 35-40 years after the original exposure, with life expectancy then 12-18 months. Given the great use of asbestos during the 20th century and this long latency period, it is no surprise that cases of mesothelioma continue to rise. There is no known cure for mesothelioma: traditional chemotherapeutic treatments have had little impact on the disease and radiotherapy or partial pleurectomy have only very limited impact on life expectancy. However, very little in the way of mesothelioma research is taking place, as it is frequently not considered to be a ‘big enough market’ (<1% of all cancers in the U.K., approx. 2300 deaths per annum) and consequently there are currently no drugs in development for this disease. A second reason for this is that there have been no reported good lead compounds (natural products) as a starting point for the drug discovery process. Until now. There are now a very small number of natural products which demonstrate activity against mesothelioma. First reported in 2012, and isolated from Saccharopolyspora sp. RL78, the natural product termed JBIR-102 possesses a unique structural architecture, and is only the third natural product to be isolated to exhibit activity against human malignant pleural mesothelioma. The aza-silyl-Prins reaction has been developed within our research group as a rapid method to prepare aza-bicycles – structural architectures found in many alkaloids and natural products, and crucially at the centre of JBIR-102. The aim of the project, therefore, is to optimise the aza-silyl-Prins reaction and then investigate its application in the synthesis of JBIR-102. A collaboration with a specialist cancer biology group will see all the compounds prepared evaluated against mesothelioma cell lines. This will be the first study of this kind.

Publications

List of publications.
year	authors and title	journal	last update
2018	Ramana R. Mittapalli, Sebastien J. J. GuesnÃ©, Robert J. Parker, Wim T. Klooster, Simon J. Coles, John Skidmore, Adrian P. Dobbs The Asymmetric Aza-silyl-Prins Reaction: Synthesis of Enantiopure Piperidines published pages: in press, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.8b03283	Organic Letters	2019-05-22

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