Dialkylsilanediols are a novel class of non-hydrolyzable analogues of the tetrahedral intermediate of amide hydrolysis, shown to be good inhibitors of HIV-1 protease, angiotensin converting enzyme (ACE), and thermolysin. An impediment to utilization of these silanediol structures, however, has been the methods for their assembly. This research describes the reductive lithiation of hydridosilanes and alkoxysilanes, and the use of the resulting silyl anions to develop efficient methods to synthesize silanediol precursors. In the first part of research, lithiation of hydridosilanes was studied. As part of this study, a simple 1H NMR method was developed for monitoring and analyzing the progress of lithiation. In addition, this method was converted to a titration for silyllithium reagents using BHT as an internal standard. Silanediols 107 and 177 are analogues of a potent chymase inhibitor, NK-3201 (82). In the second part, diphenylsilanes 108 and 170, precursors to silanediols 107 and 177, were synthesized using addition of silyllithium to sulfinimine 113 as a key step. In the third part, lithiation of alkoxysilanes was studied. (Si,O)-Dianions, generated from lithiation of silane alcohol 175 or 2,2-diphenyl-1-oxa-2-silacyclopentane (225), were reacted with a wide variety of electrophiles to give potentially useful silicon-containing building blocks. Addition of the (Si,O)-dianion 284 to sulfinimines gave silanediol inhibitor precursors with full control of stereochemistry. In the last part, a new method featuring 1,1-diphenyl-2-azaallyllithium chemistry were utilized to synthesize a series of protected α-amino silanes 323, 329 - 331. / Chemistry
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/821 |
| Date | January 2012 |
| Creators | Bo, Yingjian |
| Contributors | Sieburth, Scott McNeill, Andrade, Rodrigo B., Davis, Franklin A., Cannon, Kevin C. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 371 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/803, Theses and Dissertations |
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