Synthetic studies directed towards the antineoplastic macrolide bryostatins.

Synthetic studies directed towards the antineoplastic macrolide bryostatins.

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dc.contributor.advisor Roy, R., en
dc.contributor.author Rey, Allan W. en
dc.date.accessioned 2009-03-20T20:27:14Z
dc.date.available 2009-03-20T20:27:14Z
dc.date.created 1990 en
dc.date.issued 2009-03-20T20:27:14Z
dc.identifier.citation Source: Dissertation Abstracts International, Volume: 52-12, Section: B, page: 6372. en
dc.identifier.isbn 9780315623330 en
dc.identifier.uri http://hdl.handle.net/10393/5938
dc.description.abstract This thesis describes stereocontrolled and practical routes to the C(1)-C(9), C(17)-C(20), and C(21)-C(27) synthons of bryostatins, which are a closely related family of 20-membered ring lactones embedding 1,3-polyol units. Bryostatins are isolated in minute quantities from the marine Bryozoan Bugula neritina and possess exceptional antineoplastic activity. Membrane-enclosed enantioselective enzymatic hydrolysis was successfully employed for the generation of gram quantities of the versatile building block (3R)-methoxymethoxypentadioic acid, monomethyl ester (51) (Chapter 2). This compound was used in the synthesis of the C(1)-C(5) segment of bryostatins. Preliminary synthetic studies towards the C(1)-C(9) subunit are described in Chapter 3. Wittig and dithiane approaches were unfortunately unsuccessful for the connection of an enzymatically derived 5 carbon unit with a D-pantolactone derived 4 carbon unit. Chapter 4 describes the practical synthesis of the C(1)-C(9) fragment of bryostatin in forms suitable for both structure/activity studies and synthetic elaboration. The pivotal step utilized a diastereoselective Mukaiyama aldol condensation of a diketene derived silylenol ether with an enzymatically derived chiral $\beta$-alkoxyaldehyde. Chapter 5 details the conversion of D-pantolactone and of D-galactono-1,4-lactone into the C(17)-C(20) and C(21)-C(27) synthons of bryostatins via a chiron approach. A study of nucleophilic additions onto chiral substituted $\gamma$-lactol templates is discussed in Chapter 6. This provided valuable information regarding the coupling of the C(17)-C(20) and C(21)-C(27) segments of bryostatins. As well, the results demonstrate the potential utility of $\gamma$-lactols as templates--a relatively unexplored area in asymmetric synthetic chemistry. en
dc.format.extent 251 p. en
dc.publisher University of Ottawa (Canada). en
dc.subject.classification Chemistry, Biochemistry. en
dc.title Synthetic studies directed towards the antineoplastic macrolide bryostatins. en
dc.type Ph.D.Thesis (Ph.D.)--University of Ottawa (Canada), 1990. en

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