Studies on the effects of various functional groups on the northern hemisphere of bryostatin through synthesis

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Title Studies on the effects of various functional groups on the northern hemisphere of bryostatin through synthesis
Publication Type dissertation
School or College College of Science
Department Chemistry
Author Rudra, Arnab
Date 2014
Description Bryostatin 1 is a complex natural product that was originally isolated by Pettit from the bryozoan Bugula neritina. Its intriguing structural complexity and remarkable biological profile against several human diseases such as cancer, Alzheimer's disease, HIV, and stroke have put bryostatin 1 in the forefront of research. The mechanism by which bryostatin mediates these effects are thought to be related to its ability to activate the protein kinase C (PKC) family of signaling enzymes. However, bryostatin is unique compared to most other known PKC activators such as the phorbol esters, as it is not a tumor promoter. The reasons behind bryostatin's distinct biological profile remain unknown and are of great interest for the development new drug leads that target PKC. The work presented in this dissertation deals with the synthesis and biological evaluation of bryostatin 1 analogues modified in the northern hemisphere of the molecule. Specifically, the role of various substituents in the A and B ring region has been investigated by synthesizing Merle 30, 32, 34, and 38. This study suggested that these functional groups do not by themselves serve as functional switches between the PMA versus bryostatin 1-like activity of bryostatin analogues. Analogues with more polar groups in the A, B ring region tend to behave like bryostatin 1 as opposed to PMA. However, analogues with similar polarity in the northern hemisphere to that of bryostatin may not necessarily follow this trend as demonstrated via studies on Merle 34 and 38.
Type Text
Publisher University of Utah
Subject Chemistry; Biochemistry; Organic chemistry
Dissertation Name Doctor of Philosophy
Language eng
Rights Management ©Arnab Rudra
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s6vq77m4
Setname ir_etd
ID 1353903
Reference URL https://collections.lib.utah.edu/ark:/87278/s6vq77m4
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