Solid natural product synthesis using

Baxendale IR, Lee A-L, Ley SV (2001) A concise synthesis of the natural product carpanone using solid-supported reagents and scavengers. Synlett 482-484... 

Triazenes are disguised diazonium ions which can be released under very mild acidic conditions. Inspired by the use of triazenes in natural product synthesis by Nicolaou et al. [127] and the pioneering work of Moore et al. [128, 129] and Tour et al. [130] in the synthesis of triazenes on a solid support and the final detachment to give iodoarenes, a whole set of triazene-based linkers has been developed (Tab. 3.10) [131]. The arene diazonium salts generated from the triazene linkers offer diverse opportunities for multifunctional cleavage. Two linkers based on tria-... 

CONTENTS Preface, Brian Hatton. Applications of Ring Strain in Natural Product Synthesis, James D. White and Nadine Chauyi Lee. Uses of the Vacuum Gas-Solid Reaction Procedure in Synthesis, W. E. Billups and Benny E. Amey, Jr. Polysubstituted Cubanes Towards Complete Systematic Substitution of the Cubane Nucleus, John Tsanaktsidis. A Personal Perspective on Norbomenes, Cyclobutenes, and Other Ring-Strained Dienophiles in Organic Synthesis, Ron N. Warrener. Synthetic Studies Related to Fullerenes and Fullerene Fragments, Goverdhan Mehta and H. Surya Prakash Rao. Index. 

Early reported applications of this technique were the preparation of a 24-member peptide library [83], of a 125-member tripeptide-substituted cinnamic acid library tested for inhibition of tyrosine phosphatase PTP1B [83], of a 64-member peptide-like library [83] and of libraries based on a natural product, epothilone, using also new polystyrene grafted solid supports [84], Other applications, ranging from l,5-benzodiazepin-2-one library synthesis [85] to chalcone library synthesis [86], were also recently reported. Commercialization of the basic components for this technique [87] (reaction supports and vessels, tags, software, sorters, reaction stations, and so on) will ensure its quick and effective use in combinatorial chemistry and also the implementation of new technical features and possibilities for more complex and demanding applications in future. 

Deshpande [74], has carried out carbon-carbon bond formation on a solid support using a polymer-supported aryl iodide and vinyl (or aryl) tins. In the area of natural-product synthesis. Overman and co-workers have carried out total syntheses of (—) and (+)-strychnine which include an aryltin/CO/alkenyltin coupling step [75] (a technique introduced earlier by Stille [1]). Very recently, Heathcock and co-workers have reported total syntheses of (—)-papuamine and (—)-haliclonadiamine which include a key step in which a 1,3-diene unit is constructed by coupling two alkenyltin moieties thus reaction (Scheme 4-27) only proceeds in the presence of copper (I) iodide [76]. 

As a source of novel chemical structures, natural products are now rivaled by the revolution that is combinatorial chemistry by which a vast number of compounds may be made from a relatively small number of starting compounds, or monomers (87). An alliance of natural products chemistry with combinatorial chemistry has resulted m the development of several libraries of natural product derivatives, using natural products as templates (88) and as targets for total synthesis on solid phase (89). Whereas natural products have often been the target or the starting point for synthetic chemists, the use of natural products as combinatorial chemistry monomers is likely to increase enormously the numbers of natural product-denved structures available for testing. 

The asymmetric epoxidation of functionalized alkenes still attracts considerable attention. Synthetic chemists continue to be in search of new and improved routes to epoxides, since they provide versatile intermediates for natural product synthesis. The topic of preparative techniques for chiral epoxides is seldom broached without the mention of the Sharpless epoxidation. Indeed, the impact of this protocol cannot be overestimated, as new applications continue to be reported. For example, linear poly(tartrate ester) ligands have been used this past year to generate a solid-supported Sharpless-type catalyst <97CC123>. 

The Kolbe-Schmitt reaction has been used as a key step in natural product synthesis. The early syntheses of isotubaic acid (Rotenic acid) used a Kolbe-Schmitt reaction in the final step. " Shriner and co-workers converted isotubanol (22) to its sodium salt under anhydrous conditions, then heated the phenoxide with solid carbon dioxide at 180 °C in a sealed reaction vessel to give an 86% yield of the natural product. Sheehan and co-workers also used the Kolbe-Schmitt reaction to prepare an early intermediate in the synthesis of gossypol where thymol is efficiently converted to o-thymotic acid in 65% yield. ... 

Cathodic cyclization reactions have supphed and continue to provide a fertile territory for the development and exploration of new reactions and the determination of reaction mechanism. Two areas that appear to merit additional exploration include the application of existing methodology to the synthesis of natural products, and, more significantly, a systematic assessment of the factors associated with the control of both relative and absolute stereochemistry. Until there is a solid foundation to which the non-electrochemist can confidently turn in evaluating the prospects for stereochemical control, it seems somewhat unlikely that electrochemically-based methods will see widespread use in organic synthesis. Fortunately, this comment can be viewed as a challenge and as a problem simply awaiting creative solution. 

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