Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C
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The Ohio State University / OhioLINK
2012
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu13545603252021-08-03T06:06:46Z Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C Wu, Dimao Chemistry <p>Marine natural products phorboxazoles, first isolated in 1995 from the Indian Ocean sponge Phorbas sp., displayed remarkable inhibition of cell growth against the a series of tumor cell lines. Among the most powerful cytostatic agents people have discovered, phorboxazoles have attracted organic chemistry community to engage in the campaign to open a synthetic route in replace of isolation from their natural source since the first total synthesis of phorboxazole A was reported by Forsyth and co-workers in 1998. As the synthetic art advanced in long term exploration, many analogues derived from phorboxazoles were designed, synthesized and investigated for structure-activity relationship (SAR) related with further optimized biological activities. Described herein is an enhanced synthesis of phorboxazole C31-C46 tail domain based on stereoselective vinylogous Mukaiyama aldol reaction and modified Julia olefination. Two reliable and practical routes arose from different sources of chiral skeleton were developed respectively. Several novel phorboxazole tail domain oxazole or non-oxazole analogues were prepared from the advanced ester precursor, ready for further bioassays.</p><p>Amphidinolides represent a large structurally varied family of marine-derived macrolides isolated from symbiotic dinoflagellates Amphidinium sp. which originated from Okinawan aceol flatworm Amphiscolops sp.. Among the known amphidinolides, the members of amphidinolide C subgroup including Amphidinolide C, C2, C3, F share identical 25-memebered macrolide moiety while attaching with different ployene side chains. Amphidinolide C, the most abundant subgroup-member bearing a free C29-OH, was the only compound displaying strong cytotoxicity in the inhibitory testing against murine lymphoma cell line L1210 and human epidermoid carcinoma cell line KB. Due to limited natural source and remarkable in vitro cytotoxicities, amphidinolide C would be another ideal target for organic synthetic communities to explore a total synthesis in additional to reconfirming the proposed structure. Since 2004, amphidinolide C has become one of top attractive targets for total synthesis as at least ten reports about synthetic studies of amphidinolide C have been published. Here several related fragment syntheses and attempted assembly of building blocks based on dithiane alkylation and organochromium/organonickel chemistry were reported and discussed. The synthesis of C1-C14 fragment was settled on alkenylation of aldehyde followed by Peterson olefination of highly inert ketone. Furthermore, the revised C15-C25 fragment synthesis featured modified Mukaiyama aerobic alkenol cyclization and sulfur-directed regiocontrolled Wacker oxidation of internal alkene.</p> 2012-12-18 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1354560325 http://rave.ohiolink.edu/etdc/view?acc_num=osu1354560325 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Chemistry |
| spellingShingle |
Chemistry Wu, Dimao Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C |
| author |
Wu, Dimao |
| author_facet |
Wu, Dimao |
| author_sort |
Wu, Dimao |
| title |
Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C |
| title_short |
Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C |
| title_full |
Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C |
| title_fullStr |
Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C |
| title_full_unstemmed |
Synthetic Studies on Phorboxazole Tail Domain and Amphidinolide C |
| title_sort |
synthetic studies on phorboxazole tail domain and amphidinolide c |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1354560325 |
| work_keys_str_mv |
AT wudimao syntheticstudiesonphorboxazoletaildomainandamphidinolidec |
| _version_ |
1719431104188907520 |