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Studies toward the synthesis of the C19 quassinoid polyandrane

Donahue, Matthew G
http://rave.ohiolink.edu/etdc/view?acc_num=osu1127227359

Abstract Details

2005, Doctor of Philosophy, Ohio State University, Chemistry.
This thesis describes exploratory research aimed toward synthesizing the C19 quassinoids, 5(R)- and 5(S)-polyandrane 3 and 4. The polyandranes are degraded triterpenes that have been isolated from Ailanthus malabarica, Castela texana, and Simaba cedron. They have highly oxygenated pentacyclic carbon frameworks decorated with nine contiguous stereocenters. While no biological studies have been published for the polyandranes at this time, quassinoids in general have been shown to have potent antitumor activity. Our own contribution to this area relies on the use of a 5-hexenyl radical cyclization to prepare the BC ring trans-perhydroindan substructure. In a model study, we have shown that a 5-endo-trig cycloetherification of symmetrical diol 243 initiated with N-bromosuccinimide afforded 6-oxabicyclo[3.2.1]octane 244 in quantitative yield. This reaction set the correct relative stereochemistry of C(8) to C(11). Swern oxidation of primary alcohol 244 gave aldehyde 245 in excellent yield. A vinylogous Mukaiyama aldol reaction of 245 with (Z)-1-methoxy-3-methylidene-1-trimethysilyloxyhexa-1,5-diene 284 promoted by titanium tetrachloride furnished alcohol 285 in 51% yield. The aldol proceeded via Felkin addition to set the correct C(7) alcohol stereocenter. A 5-exo-trig free radical cyclization of 285 gave tricycle 288 in 63% yield. This reaction set the C(9) center relative to C(8) and C(11). In a second model study, we addressed the C(11) oxidation state of 3 and 4. We prepared aldehyde 350 in 55% yield over four steps from 3-methoxy-5-methylbenzoic acid 219. Sulfur ylide epoxidation of 350 with dimethyloxosulfonium methylide 356 gave epoxide 354 with correct C(7) stereochemistry in 30% yield. Ring opening of epoxide 354 with the lithium anion of ethyl propiolate 355 promoted with boron trifluoride etherate gave alkyne 353 in 59% yield. A 5-exo-dig free radical cyclization of 353 with 10 equivalents of tri-n-butyltin hydride gave tricycle 352 in 75% isolated yield. This model compound contained the C(7) and C(11) fragment in the correct oxidation states, a functional handle for elaboration of the A ring, and a handle for D ring annulation.
David Hart (Advisor)
478 p.
Chemistry, Organic
quassin; quassinoid; polyandrane; free radical cyclization; alkyne; epoxide

Recommended Citations

Citations

  • Donahue, M. G. (2005). Studies toward the synthesis of the C19 quassinoid polyandrane [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1127227359

    APA Style (7th edition)

  • Donahue, Matthew. Studies toward the synthesis of the C19 quassinoid polyandrane. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1127227359.

    MLA Style (8th edition)

  • Donahue, Matthew. "Studies toward the synthesis of the C19 quassinoid polyandrane." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1127227359

    Chicago Manual of Style (17th edition)

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© 2005, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.