eprintid: 9766 rev_number: 5 userid: 6 dir: disk0/00/00/97/66 datestamp: 2011-11-10 20:05:55 lastmod: 2016-11-15 13:51:59 status_changed: 2011-11-10 20:05:55 type: thesis_degree metadata_visibility: show contact_email: jared.moretti@gmail.com item_issues_count: 0 eprint_status: archive creators_name: Moretti, Jared Daniel creators_email: jared.moretti@gmail.com title: Fluorous Mixture Synthesis of Sch725674 and its Fifteen Stereoisomers ispublished: unpub divisions: sch_as_chemistry full_text_status: public keywords: allylboration; fluorous mixture synthesis; fluorous tag; macrolide; natural products; ring-closing metathesis; stereoisomer library; HPLC; macrolactone abstract: Sch725674 is a 14-membered macrolactone isolated from the culture of an Aspergillus sp. by a group at Schering-Plough in 2005. A two-dimensional structure with four stereocenters was proposed for Sch725674, leaving sixteen candidate stereostructures for the natural product. Herein, we report the fluorous mixture synthesis (FMS) of all sixteen candidate stereoisomers of Sch725674 to determine its relative and absolute configuration. Initially, the synthesis of a single stereoisomer of Sch725674 was executed to secure a route to the natural product and to confirm the 2D connectivity of Sch725674. The synthesis established in the single isomer pilot study was then applied to the FMS of the 4,5-trans-dihydroxy isomer family of Sch725674, in which all eight members bear a trans relationship between the C4 and C5 stereocenters. An eight-member library of ring-open Sch725674 analogs was also prepared by demixing and detagging two intermediate mixtures from the FMS of the 4,5-trans-dihydroxy isomer family. We then executed a second, parallel FMS of the 4,5-cis-dihydroxy family of Sch725674, in which each member has a cis relationship between the C4 and C5 stereocenters. All three of these libraries employed a new minimalist tagging strategy which used two sorting tags in an FMS, only one of which was fluorous. By comparing spectra of the macrocycle library members with each other and the natural product, we confidently assigned the absolute configuration of natural Sch725674 as (4R,5S,7R,13R). date: 2011-01-30 date_type: completed institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Curran, Dennis P etdcommittee_name: Doemling, Alexander etdcommittee_name: Wilcox, Craig etdcommittee_name: Floreancig, Paul etdcommittee_email: curran@pitt.edu etdcommittee_email: asd30@pitt.edu etdcommittee_email: daylite@pitt.edu etdcommittee_email: florean@pitt.edu etdcommittee_id: CURRAN etdcommittee_id: ASD30 etdcommittee_id: DAYLITE etdcommittee_id: FLOREAN etd_defense_date: 2010-12-03 etd_approval_date: 2011-01-30 etd_submission_date: 2010-11-22 etd_access_restriction: 5_year etd_patent_pending: FALSE assigned_doi: doi:10.5195/pitt.etd.2011.9766 thesis_type: dissertation degree: PhD committee: Dennis P. Curran (curran@pitt.edu) - Committee Chair committee: Alexander Doemling (asd30@pitt.edu) - Committee Member committee: Craig Wilcox (daylite@pitt.edu) - Committee Member committee: Paul Floreancig (florean@pitt.edu) - Committee Member etdurn: etd-11222010-191153 other_id: http://etd.library.pitt.edu/ETD/available/etd-11222010-191153/ other_id: etd-11222010-191153 citation: Moretti, Jared Daniel (2011) Fluorous Mixture Synthesis of Sch725674 and its Fifteen Stereoisomers. Doctoral Dissertation, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/9766/1/Moretti_Jared2010.pdf