Moura, Gustavo
(2008)
APPLICATION OF FLUOROUS MIXTURE SYNTHESIS (FMS) FOR THE SYNTHESIS OF NATURAL PRODUCT STEREOISOMER LIBRARIES: TOTAL SYNTHESIS OF EIGHT DIASTEREOMERS OF PASSIFLORICIN A AND STUDIES ON A CONVERGENT SYNTHESIS OF 6-EPI-DICTYOSTATIN.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Passifloricin A, a natural product isolated from the tree Passiflora foetida is a polyol δ-lactone containing four stereocenters. The Fluorous Mixture Synthesis (FMS) of all eight diastereomers of passifloricin A is reported herein. FMS is a technique that exploits the simplicity and velocity of working with mixtures of compounds, yet still permits for a systematic separation of the mixtures to provide individual pure stereoisomers or analogs. Utilizing a multiple-tag FMS strategy we successfully obtained two mixtures of four double tagged quasiisomers that were separated (demixed) by fluorous HPLC to provide the eight quasiisomers in a systematic fashion. The eight quasiisomers were individually deprotected to provide the eight diastereomers of passifloricin A. Diastereomer (SRRR)-3 spectroscopic data matched the spectroscopic data for natural and synthetic passifloricin A. Dictyostatin, a marine sponge-derived macrolactone has been extensively studied in our group because of its high potency as a microtubule-stabilizing agent. Our group, based on SAR studies, synthesized the four times more potent 6-epimer (6-epi-dictyostatin 36). We hypothesized a more convergent approach for the synthesis of 36 by introducing dienyl ester bottom fragment 41, easily synthesized by the ene-diene metathesis. We successfully coupled the fragments via ring closing metathesis of silaketal 89 to provide key advanced intermediate 94 after deprotection. The final steps led to the synthesis of 30 mg of 6-epi-dictyostatin.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
16 June 2008 |
| Date Type: |
Completion |
| Defense Date: |
19 November 2007 |
| Approval Date: |
16 June 2008 |
| Submission Date: |
16 November 2007 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
FMS; library; stereoisomers; 6-epi-dictyostatin; passifloricin |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-11162007-001904/, etd-11162007-001904 |
| Date Deposited: |
10 Nov 2011 20:05 |
| Last Modified: |
15 Nov 2016 13:51 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/9689 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}