Studies directed toward the synthesis of aspidophytine. Snyder discuss in detail the most impressive accomplishments in. Nielsen book data summary 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 parent reagent and its hcl salt present stability and detonation risks, but the hydrogen sulfate salt is significantly more stable. Jul 20, 2006 in 1973, cava and yates reported on the structural determination of haplophytine 4, a dimeric indole alkaloid isolated from the leaves of haplophyton cimicidum.
Jun 03, 20 the feasibility of this approach was demonstrated with the total synthesis of aspidophytine in 18 steps from 4,4. A total synthesis of aspidophylline a, a pentacyclic akuammilinetype monoterpene indole alkaloid, is described. An updated synthesis of the diazotransfer reagent imidazole. Everninomicin,3841 nicolaou biscorbicillinoids nicolaou aspidophytine corey cp.
A general approach toward the asymmetric total synthesis of various aspidosperma alkaloids includes the combination of a c h bond activation with a heck. The tetrathiafulvaleneinduced radicalpolar crossover reaction has been applied to the total synthesis of the pentacyclic alkaloid aspidospermidine. Li j, jeung s, esser l, harran pg 2001 total synthesis of nominal diazonamidespart 1. Aspidophytine is an indole alkaloid that has attracted a lot of attention from synthetic chemists. Sumi s, matsumoto k, tokuyama h, fukuyama t 2003 enantioselective total synthesis of aspidophytine. To date, five total syntheses of the lefthalf segment, aspidophytine 3, have been reported. Advances in the total syntheses of complex indole natural. Alphahaloalkylboronic esters in asymmetric synthesis. Enantioselective total synthesis of aspidophytine feng he, yunxin bo, jason d. Corey department of chemistry and chemical biology harvard university cambridge, massachusetts 028. Synthetic scheme for total synthesis of aspidospermidine. Synthesis of the left hand side lhs requires the creation of four rings, so the group made life as easy as possible by starting with two in the starting materials.
Its total synthesis 123 in 1987 by our group represented the first breakthrough within this class of complex molecules. Pedro juan llabrescampaner, rafael ballesterosgarrido, rafael ballesteros, and belen abarca. The first total synthesis of aspidophytine 7 was completed by the corey group in 1999. The art and science of total synthesis at the dawn of the twentyfirst century. Group meeting papers 2008 here is a list of research papers that were presented for discussion in our 2008 weekly group meetings. Commercially available aniline was iodinated using ic1 73% and the resulting. The original article is trackable via the references option. Classics in total synthesis ii 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. Snyder discuss in detail the most impressive accomplishments in natural product total synthesis during the 1990s and the first years of the 21st century. Total synthesis of haplophytine by fukuyama, tokuyama. Group meeting papers 2008 sloan kettering institute.
Aspidosperma terpenoid alkaloids biosynthetic origin. This total synthesis featured the recognition of subtle symmetry elements within the target molecule that allowed the utilization of the same starting material to construct two, seemingly unrelated, intermediates and the angew. Enantioselective total synthesis of aspidophytine journal of the american chemical society acs publications enantioselective total synthesis of aspidophytine feng he, yunxin bo, jason d. Classics in total synthesis ii is the long awaited sequel to classics in total synthesis. Oct 27, 2003 classics in total synthesis ii 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. A concise asymmetric total synthesis of aspidophytine. Enantioselective total synthesis of aspidophytine journal of the american chemical society. This interest has resulted in the of publication of two general scientific books. Imidazole1sulfonyl azide and salts thereof are valuable reagents for diazotransfer reactions, most particularly conversion of primary amines to azides. Enantioselective total synthesis of aspidophytine he, f bo, y altom, j. The preparation of 16 was carried out in five steps in 36% overall yield starting from aniline and is summarized in scheme 3.
What is the most ingenious and elegant synthesis step you. Journal of the american chemical society 2018, 140 3, 919925. An exceptionally short and simple enantioselective total synthesis of pentacyclic triterpenes of the. Its total synthesis123 in 1987 by our group represented the first breakthrough within this class of complex molecules. It is one of the two components of the dimer haplophytine in his suicide note, harvard doctoral student jason altom mentioned his stress in attempting to devise a.
Protracted lowdose effects on human endothelial cell proliferation and survival in vitro reveal. S a snyder nicolaou and snyder present top experts from the field of total synthesis to include figures and diagrams, and all the essential details, such as elegant reaction chains or asymmetric process steps. Graduate thesis or dissertation total synthesis of. An enantioselective total synthesis of aspidophytine is described. Not only a natural product but aspidophytine is also a building block on the way towards haplophytine a very challenging natural product. The indole fragment bearing a cisalkene substituent was efficiently prepared. A total synthesis of aspidophytine i was accomplished by employing a newly developed strategy for the enantiospecific syntheses of aspidosperma alkaloids. Thus, this article should rather say that jason altom was the first to succeed in the synthesis of aspidophytine he actually is on the relevant paper j.
Total synthesis of the monoterpenoid indole alkaloid. A third ring was soon added to this indole fragment by imine formation. It is an ideal synthesis in pretty much every definition and was done in 1917. A concise asymmetric total synthesis of aspidophytine, k. It is one of the two components of the dimer haplophytine. Application to the total synthesis of 2,7,8epiperhydrohistrionicotoxin. The key steps involve a novel ketenelactonization reaction of a chiral vinyl sulfoxide marino annulation reaction to set up the chiral quaternary carbon center, and a tandem michael addition.
Abstract an expedient asymmetric total synthesis of aspidophytine is reported. Snyder discuss in detail the most impressive accomplishments in natural product. An expedient asymmetric total synthesis of aspidophytine is reported. Enantioselective total synthesis of aspidophytine organic letters. Fischer indole synthesis applied to the total synthesis of natural.
Snyder 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. It was obvious in retrospect but at the time, that was an amazing synthesis. A highly convergent strategy involving the sequential annulation of vinyl iodide 5 with indole 6 exploits varying modes of indole reactivity to provide aspidophytine in 23% over six steps from 5. An extract of the cockroach plant, aspidophytine is an insecticidal substance particularly effective against cockroaches. Complete schematic view of the 1999 aspidophytine s synthesis performed by elias j. An updated procedure for the largescale synthesis of this salt avoids isolation or concentration of.
A total synthesis of aspidophytine was accomplished by employing a newly developed strategy for the enantiospecific syntheses of aspidosperma alkaloids. This barcode number lets you verify that youre getting exactly the right version or edition of a book. Papers are selected by group members as a means to broaden our knowledge in chemistry and chemical biology. Enantioselective total synthesis of aspidophytine journal. The key steps involve a novel ketenelactonization reaction of a chiral vinyl sulfoxide marino annulation reaction to set up the chiral quaternary carbon center, and a tandem michael addn. I still think that robinsons one step synthesis of tropinone is one of the most elegant syntheses ever done. A novel total synthesis of aspidospermidine journal of. Part of the topics in heterocyclic chemistry book series topics, volume 26. Thesynthesis features a highly efficient construction of the aromatic fragment 3incorporating tbs protection of the aniline, a significantly improved synthesis of. A highly convergent strategy involving the sequential annulation of vinyl. Total synthesis of the caged indole alkaloid arboridinine enabled by azaprins and metalmediated cyclizations. Cheminform is a weekly abstracting service, delivering concise information at a glance that was extracted from about 100 leading journals. Application of the rhii cyclizationcycloaddition cascade.
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