Not only a natural product but aspidophytine is also a building block on the way towards haplophytine a very challenging natural product. A concise asymmetric total synthesis of aspidophytine journal of. It is an ideal synthesis in pretty much every definition and was done in 1917. Everninomicin,3841 nicolaou biscorbicillinoids nicolaou aspidophytine corey cp.
An enantioselective total synthesis of aspidophytine is described. The preparation of 16 was carried out in five steps in 36% overall yield starting from aniline and is summarized in scheme 3. Its total synthesis123 in 1987 by our group represented the first breakthrough within this class of complex molecules. A concise asymmetric total synthesis of aspidophytine, k.
Enantioselective total synthesis of aspidophytine organic letters. Construction of the aspidosperma skeleton was executed by fischer indole synthesis between substituted phenylhydrazines and tricyclic aminoketone. Studies directed toward the synthesis of aspidophytine. Advances in the total syntheses of complex indole natural. Imidazole1sulfonyl azide and salts thereof are valuable reagents for diazotransfer reactions, most particularly conversion of primary amines to azides. 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. Commercially available aniline was iodinated using ic1 73% and the resulting. An extract of the cockroach plant, aspidophytine is an insecticidal substance particularly effective against cockroaches. Classics in total synthesis ii is the long awaited sequel to classics in total synthesis.
The original article is trackable via the references option. 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. 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. Alphahaloalkylboronic esters in asymmetric synthesis. Snyder discuss in detail the most impressive accomplishments in natural product total synthesis during the 1990s and the first years of the 21st century. To access a cheminform abstract of an article which was published elsewhere, please select a full text option.
Enantioselective total synthesis of aspidophytine journal of the american chemical society. Total synthesis of the caged indole alkaloid arboridinine enabled by azaprins and metalmediated cyclizations. This interest has resulted in the of publication of two general scientific books. 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. It is one of the two components of the dimer haplophytine. Application of the rhii cyclizationcycloaddition cascade. The indole fragment bearing a cisalkene substituent was efficiently prepared. Part of the topics in heterocyclic chemistry book series topics, volume 26. The art and science of total synthesis at the dawn of the twentyfirst century. A total synthesis of aspidophytine was accomplished by employing a newly developed strategy for the enantiospecific syntheses of. 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. A third ring was soon added to this indole fragment by imine formation.
Altom jd, corey ej 1999 enantioselective total synthesis of aspidophytine. The rapid and direct asymmetric synthesis of 33aindolylhexahydropyrroloindoline motifs is an extremely important part of the total synthesis of several alkaloid structures. 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. To date, five total syntheses of the lefthalf segment, aspidophytine 3, have been reported. Enantioselective total synthesis of aspidophytine feng he, yunxin bo, jason d. 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. Group meeting papers 2008 sloan kettering institute.
Enantioselective total synthesis of aspidophytine i. Protracted lowdose effects on human endothelial cell proliferation and survival in vitro reveal. An updated procedure for the largescale synthesis of this salt avoids isolation or concentration of. Enantioselective total synthesis of aspidophytine journal. 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.
A total synthesis of aspidophytine was accomplished by employing a newly developed strategy for the enantiospecific syntheses of aspidosperma alkaloids. Aspidosperma terpenoid alkaloids biosynthetic origin. A total synthesis of aspidophytine i was accomplished by employing a newly developed strategy for the enantiospecific syntheses of aspidosperma alkaloids. A general approach toward the asymmetric total synthesis of various aspidosperma alkaloids includes the combination of a c h bond activation with a heck. Group meeting papers 2008 here is a list of research papers that were presented for discussion in our 2008 weekly group meetings. An exceptionally short and simple enantioselective total synthesis of pentacyclic triterpenes of the. A novel total synthesis of aspidospermidine journal of. Its total synthesis 123 in 1987 by our group represented the first breakthrough within this class of complex molecules.
What is the most ingenious and elegant synthesis step you. Enantioselective total synthesis of aspidophytine he, f bo, y altom, j. I still think that robinsons one step synthesis of tropinone is one of the most elegant syntheses ever done. Jun 03, 20 the feasibility of this approach was demonstrated with the total synthesis of aspidophytine in 18 steps from 4,4. 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 first total synthesis of aspidophytine 7 was completed by the corey group in 1999. Herein, the tetraoxobispidine approach to lupine alkaloids was extended to a total synthesis of sparteine dl1, a second generation improved route to. Total synthesis of haplophytine by fukuyama, tokuyama.
A highly convergent strategy involving the sequential annulation of vinyl. This barcode number lets you verify that youre getting exactly the right version or edition of a book. 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. A concise asymmetric total synthesis of aspidophytine. Papers are selected by group members as a means to broaden our knowledge in chemistry and chemical biology. The tetrathiafulvaleneinduced radicalpolar crossover reaction has been applied to the total synthesis of the pentacyclic alkaloid aspidospermidine.
The feasibility of this approach was demonstrated with the total synthesis of. Sumi s, matsumoto k, tokuyama h, fukuyama t 2003 enantioselective total synthesis of aspidophytine. Total synthesis of the monoterpenoid indole alkaloid. Application to the total synthesis of 2,7,8epiperhydrohistrionicotoxin. An updated synthesis of the diazotransfer reagent imidazole.
Aspidophytine is an indole alkaloid that has attracted a lot of attention from synthetic chemists. The parent reagent and its hcl salt present stability and detonation risks, but the hydrogen sulfate salt is significantly more stable. Cheminform is a weekly abstracting service, delivering concise information at a glance that was extracted from about 100 leading journals. Synthetic scheme for total synthesis of aspidospermidine. Graduate thesis or dissertation total synthesis of. Snyder discuss in detail the most impressive accomplishments in. Corey department of chemistry and chemical biology harvard university cambridge, massachusetts 028. Snyder discuss in detail the most impressive accomplishments in natural product. Abstract an expedient asymmetric total synthesis of aspidophytine is reported.
Journal of the american chemical society 2018, 140 3, 919925. 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. 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. It was obvious in retrospect but at the time, that was an amazing synthesis. A total synthesis of aspidophylline a, a pentacyclic akuammilinetype monoterpene indole alkaloid, is described.
Complete schematic view of the 1999 aspidophytines synthesis performed by elias j. Nowadays, there has been increasing attention on the total synthesis of bioactive. Pedro juan llabrescampaner, rafael ballesterosgarrido, rafael ballesteros, and belen abarca. Thesynthesis features a highly efficient construction of the aromatic fragment 3incorporating tbs protection of the aniline, a significantly improved synthesis of. Enantioselective total synthesis of aspidophytine journal of the american chemical society acs publications enantioselective total synthesis of aspidophytine feng he, yunxin bo, jason d.
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