The total synthesis starts from a known compound and is accomplished in 17 steps with 1. Arduous natural product quests unwelcome end research. The baran group published a new 11step total synthesis of. Total synthesis of maoecrystal v ebook by jianxian gong. Give the name and the mechanism for the third step 3 o 4. Reisman of the california institute of technology, featuring as a key step the cyclization of 1 to 2, is a tribute to the power of oneelectron reduction for carbon.
A strategy for the total synthesis of maoecrystal v is presented. But yes, baran often solves a synthesis problem by throwing a few manmonths at it. Baran also sometimes fails to get a route to work despite throwing many manmonths at it. Total synthesis of maoecrystal v springer theses 2014. A concise total synthesis of maoecrystal z caltechauthors. Fan su, yandong lu, lingran kong, jingjing liu, tuoping luo. Ch functionalization for the construction of a key benzofuran intermediate enabled the first asym.
With 32 rings and 98 stereocentres, maitotoxin is the largest and most complex natural product that is neither a protein nor a polysaccharide, consisting mostly of fused cyclic ethers. Total synthesis of maoecrystal v news chemistryviews. An expedient, practical, and enantioselective route to the highly congested entkaurane diterpene maoecrystal v is presented. This is the long awaited sequel to classics in total synthesis, a book that has made its mark as a superb tool for educating students and practitioners alike in the art. Give the name and the mechanism of the first reaction 4 o 5, 2. Apr 27, 2011 the unique and complex structure of maoecrystal v 1, fig. The natural product is prepared in a longest linear sequence of 11 steps. Theres a lot of chemistry done in well plates these days, and this is the sort of reaction that youd do a thousand times on 5 mg scale and shoot the results on a gc to measure how each worked. Efficiency in natural product total synthesis by peiqiang. Nov 14, 2012 the total synthesis of racemic maoecrystal v has been accomplished. Thesynthesis features a highly efficient construction of the aromatic fragment 3incorporating tbs protection of the aniline, a significantly improved synthesis of.
In unpublished work after our synthesis we also observed the same outcome, so i am very glad they reported their findings, thomson says. Based on the information supplied by model research, the total synthesis of maoecrystal v was developed. Uniting the key organic topics of total synthesis and efficient synthetic methodologies, this book clearly overviews synthetic strategies and tactics applied in total synthesis, demonstrating how the total synthesis of natural products enables scientific and drug discovery. This is the long awaited sequel to classics in total synthesis, a book that has made its mark as a superb tool for educating students and practitioners alike in the art of organic synthesis since its introduction in 1996. The first total synthesis of maoecrystal z is described. The structural complexity of 1, coupled with its biological activity, prompted us to undertake a program directed toward its total synthesis. The zinc must be activated to facilitate this redox reaction. Optimizing one step in the total synthesis of maoecrystal v. The total synthesis of racemic maoecrystal v has been accomplished. Maoecrystal z 3 was isolated as a minor consituent from the chinese medicinal herb isodon eriocalyx. An expedient, practical, and enantioselective route to the highly congested entkaurane diterpene maoecrystal v is. The evolution of a program directed at the enantioselective total synthesis of maoecrystal v i, a highly modified entkauranoid, is described. Adding to the level of interest in maoecrystal, is its potent in vitro activity against hela cells ic 50 20 ngml.
In our laboratory these two research areas are usually closely linked. Step 7 is a reaction of enone 1 and formaldehyde to. The baran group published a new 11step total synthesis of maoecrystal v. Efficiency in natural product total synthesis organic. Total synthesis of maoecrystal v jianxian gong springer. Total syntheses of highly oxidized entkaurenoids pharicin a.
A new strategy was devised for the total synthesis of highly oxidized ent. Key steps include an intramolecular dielsalder cyclization to rapidly. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Total synthesis towards maoecrystal v isolated from the leaves of a chinese medicinal herb, isodon eriocalyx in 2004. An intramolecular rhiicatalyzed ch insertion reaction installed the tetrahydrofuran ring with requisite stereochemistry. In model study of maoecrystal v, the skeleton of the natural product was successfully established, and three contiguous chiral centers, c8, c9, c10, were also built. The synthesis features a wessely oxidative dearomatization of a phenol, an intramolecular diels. Read total synthesis of maoecrystal v by jianxian gong available from rakuten kobo. Key steps include an intramolecular dielsalder cyclization to rapidly construct the core system from simple starting materials and the creation of the ac ring transfusion through intramolecular delivery of a hydrogen to the hindered. The successful total synthesis of maoecrystal v will contribute to the development of efficient synthetic strategies for natural products and other compounds with complex structures.
The group completed the first enantioselective total syntheses of acetylaranotin 40 years after its isolation, maoecrystal z, 8demethoxyrunanine, and cepharatines a, c and d. Danishefsky, columbia university, new york, usa, describe the total synthesis of racemic maoecrystal v. The key steps of the synthesis include a diastereoselective tiiiimediated reductive epoxide coupling reaction and a diastereoselective smiimediated reductive cascade cyclization reaction. Synthesis of functionalized maoecrystal v core structures. Download it once and read it on your kindle device, pc, phones or tablets. The reisman synthesis of maoecrystal z maoecrystal z 3 was isolated as a minor consituent from the chinese medicinal herb isodon eriocalyx. Total synthesis of maoecrystal v journal of the american. Use features like bookmarks, note taking and highlighting while reading total synthesis of maoecrystal v springer theses. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to. It explores the literature to date and attempts to indicate other areas in which ultrasound may be exploited. You have access to this article please wait while we load your content. The main objectives of our research program at the university of arizona are twofold.
Maoecrystal v artiom cernijenko, rune risgaard, and phil s. Thousands of experiments help find conditions to make maoecrystal v. Review of synthetic approaches toward maoecrystal v. Reagentcontrolled stereoselectivity in titanocenecatalyzed. In the third part, the author describes the first successful total synthesis of maoecrystal v and investigates four strategies for constructing the key tetrahydrofuran oxabridge skeleton. Figure 1 from asymmetric total synthesis of maoecrystal v. Nov 15, 2012 a successful synthesis of maoecrystal v could bring with it new compounds with therapeutically exploitable anticancer activity. Journal of the american chemical society 2016, 8 30, 94259428. The key interior vicinal quaternary carbon centers will be formed via sequential bridgehead ch bond insertion and enolate. The unique and complex structure of maoecrystal v 1, fig. The enantioselective synthesis of maoecrystal v, a cytotoxic polycyclic diterpene, is described.
Research background of total synthesis of natural product maoecrystal v and its family. These transformations enabled the preparation of maoecrystal z in only 12 steps from. Key steps include an intramolecular dielsalder cyclization to rapidly construct the core system from simple starting materials and the creation of the ac ring trans fusion through intramolecular delivery of a hydrogen to the hindered. Submitted by valentin total synthesis of maoecrystal v 1. Maoecrystal v thomson, 2014 key steps in total synthesis i. A concise first total synthesis of maoecrystal v 1 is reported. The reisman paper in question is the first total synthesis of maoecrystal z published last year in jacs, and hot on the heels of the long sought after maoecrystal v which was finally pinned down by yang the year before. Strategies and tactics in organic synthesis 11 book chapter. One of such activated form of zinc employed by frankland is zinccopper couple. A concise total synthesis of maoecrystal z jacob y. Submitted by valentin total synthesis of maoecrystal v. Abstract a new strategy was devised for the total synthesis of highly oxidized ent.
The answer is 20, at least when it comes to maitotoxin, quite possibly the toughest total synthesis challenge around. Nakiterpiosin chen, 2009 harringtonolide mander, 1998 daphnilactone heathcock, 1989 7deacetoxyalcyoninacetate overman, 1995 pactamycin johnson, 20. In this thesis, the author describes the total synthesis of natural product maoecrystal v in detail. Review of synthetic approaches toward maoecrystal v organic. Reisman of the california institute of technology, featuring as a key step the cyclization of 1 to 2, is a tribute to the power of oneelectron reduction. To be fair, theres no way they didnt massively parallelize those reactions especially considering there are only two nonpi authors. Focuses on efficiency, a fundamental and important issue in natural products synthesis that makes natural product. Total synthesis of maoecrystal v springer theses kindle edition by gong, jianxian. Chemistrys toughest total synthesis challenge put on hold. An expedient, practical, and enantioselective route to the highly congested ent kaurane diterpene maoecrystal v is presented. Maoecrystal z, journal of the american chemical society, 2011, 3, 38, 14964crossref view all 52 citations.
Regan thomson from northwestern university in evanston, us, whose teams 18step maoecrystal v route was previously the shortest 3, had a similar experience. The asymmetric total synthesis of maoecrystal v, a novel cytotoxic. O o me me o me o o h total synthesis towards maoecrystal v isolated from the leaves of a chinese medicinal herb, isodon eriocalyx in 2004. Chemistrys toughest total synthesis challenge put on hold by. We report herein the development of some interesting chemistry en route to a projected total synthesis of maoecrystal v 1. Two strategies toward the total synthesis of maoecrystal v 1 culminating in the construction of core structures 2 and 3 are described.
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