Synthetic approaches to syn-diol containing biologically active compounds /

The deoxy derivative of pancratistatin 1.10 was prepared in good yield through the use of a [4+2] Diels-Alder cycloaddition and Bischler-Napieralski cyclization approach. The Bischler-Napieralski cyclization was shown to yield two additional side products 2.9, 2.10, however, under slightly modified hydrolysis conditions, the tetracyclic product 2.11 was obtained exclusively in greater than 84% yield. Initial screening of the di-hydroxylatgd derivative, and the other complementary pair analogue 1.10' previously prepared in our laboratories gave interesting results. Both of these compounds were shown to exhibit cytostatic activity; the mono-alcohol was marginally active while the di-hydroxylated analogue proved to be more potent although one to two magnitudes less potent than pancratistatin itself Human tumour cell line assay results indicated that the di-hydroxylated derivative exhibited selective cytotoxic inhibition in the following cell lines: non-small cell lung cancer line NCI-H226 (ED50 - 0.65 ^g/mL), leukemia cell lines CCRF-CEM (ED30 = 0.55 Hg/mL) and HL-60(TB) (ED50 = 0.89^ig/mL). Our results demonstrated that the pharmacophore is not a mono-alcohol, and that the minimum pharmacophore contains the hydroxyl group at the C4 position in addition to either, or both, of the hydroxyl groups present at C2 and C3.' The minimum pharmacophore has been narrowed to only three possibilities which are current synthetic targets in several research groups. The controlled Grignard addition to the tartaric acid derived bis-Weinreb amide 1.25 afforded a direct entry to a host of 1,4-diflferentiated tartaric acid derived intermediates (2.12-2.18). This potentially usefiil methodology was demonstrated through the efficient synthesis of the naturally occurring lactone 2.23, which bears the inherent syn-dio\ subunit. Based on this result, a similar approach to the synthesis of syn-dio\ bearing natural products looks very promising? A direct 2,3-diol desymmetrization method using TIPS-triflate was shown to be effective on the selective differentiation of Z,-methyl tartrate (and diisopropyl tartrate). The mono-silyl-protected intermediates 2.31 also proved to be useful when they were selectively differentiated at the 1,4-carboxyl position (2.35, 2.36) through the use of a borohydride reducing agent. Furthermore, the mono-silyl-protected derivative underwent periodate cleavage affording two synthetically useful a,P-unsaturated esters 2.43, 2.44, with one of esters being obtained via a silyl-migration method.''

Sean O'Sullivan fonds

Sean O’Sullivan was born in Hamilton, Ontario, in 1952. At an early age, he demonstrated an interest in politics. A chance meeting with John Diefenbaker in 1963, when Sean was just 11 years old, marked the beginning of his involvement with the Progressive Conservative Party. Diefenbaker became a mentor to him, and the two exchanged correspondence for many years. Sean became an active member of the Party, and his political career took off quickly. In 1965, he was elected to the executive of the Hamilton Area Young Progressive Conservatives, in 1968 was elected President, and also served as Youth Director for Diefenbaker’s re-election campaign. In 1970 he was elected President of the Ontario Young Progressive Conservatives, and in 1971 became Youth Adviser to Premier William Davis. Later that year, Diefenbaker chose Sean to be his Executive Assistant. In addition to his political activities, Sean enrolled at Brock University in 1969 to study political science. In 1972, he resigned as Diefenbaker’s assistant in order to run as a candidate for Hamilton-Wentworth in the federal election that year. At just 20 years of age, Sean was the youngest MP elected to the House of Commons. While working as an MP, Sean continued his studies at Brock University part-time, graduating with distinction. After being re-elected in 1974, he rose to greater prominence when he succeeded in having a private member’s bill passed making the beaver one of Canada’s national symbols. In 1977, he resigned as MP in order to pursue religious studies and become a Catholic priest. After completing four years of studies at the Irish College of Rome’s Gregorian University, Sean was ordained a priest in Toronto in 1981. In July, 1982, he was appointed Director of Vocations (full-time recruiter) for the archdiocese of Toronto. In this capacity, he implemented a controversial and widely publicized campaign to recruit priests. The recruitment succeeded in generating interest in the priesthood, doubling the number of students in the archdiocese. He was one of the founding members of Serra House, a residence for students considering the priesthood. After his term as Vocations Director ended in 1985, O’Sullivan became publisher of The Catholic Register, a weekly church newspaper. That same year, he was awarded an honorary doctorate from Brock University. In January 1987, he was appointed a Member of the Order of Canada. Later that year, he submitted a report to the Attorney General of Ontario, titled You’ve got a Friend, after conducting an independent review of Advocacy for Vulnerable Adults in Ontario at the request of the government. In 1983, O’Sullivan was diagnosed with leukemia. The disease went into remission after treatment, but was incurable. In 1989, he had a bone marrow transplant at Princess Margaret Hospital in Toronto, but died shortly afterwards. He was 37 years old. A memorial fund was established in his name, and included contributions from prominent business, church and political leaders such as Prime Minister Brian Mulroney, Toronto Sun Chairman Doug Crieghton and His Eminence G. Emmett Carter. The O’Sullivan family requested that Brock University be the beneficiary of the proceeds of the campaign.

Sympathy Letter from Prime Minister

A letter from Prime Minister, Brian Mulroney, expressing sympathy to the parents of Father Sean O'Sullivan. Father Sean passed away in 1989 after battling leukemia, he was 37 years old.

The Spirit of Hope: Research Centre Named in Honour of Father Sean O'Sullivan

An article in "Community Contact" (a publication by St. Joseph's Hospital, St. Joseph's Community Health Centre, and St. Joseph's Health Care Foundation) discussing the naming of the Father Sean O'Sullivan Research Centre. The article describes the time Father Sean spent at the hospital and his battle with leukemia.

Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia

cell of origin and triggering events for leukaemia are mostly unknown. Here we show that the bone marrow contains a progenitor that expresses renin throughout development and possesses a B-lymphocyte pedigree. This cell requires RBP-J to differentiate. Deletion of RBP-J in these renin-expressing progenitors enriches the precursor B-cell gene programme and constrains lymphocyte differentiation, facilitated by H3K4me3 activating marks in genes that control the pre-B stage. Mutant cells undergo neoplastic transformation, and mice develop a highly penetrant B-cell leukaemia with multi-organ infiltration and early death. These reninexpressing cells appear uniquely vulnerable as other conditional models of RBP-J deletion do not result in leukaemia. The discovery of these unique renin progenitors in the bone marrow and the model of leukaemia described herein may enhance our understanding of normal and neoplastic haematopoiesis.