Synthesis of Bioactive Natural Products

Selected examples of the synthesis of natural product starting from aldonolactones are presented in this section. 

Spirocyclic C-aryl glycosides are central structural skeletons of papulacandins that constitute a family of novel antifungal antibiotics isolated from a strain of Papularia sphaerosperna. They have shown potent in vitro antifungal activity against Candida albicans, Candida tropicalis, Pneumocystis carinii, among other microorganisms [110], 

Spirocychc C-ribosyl aromatic compounds have also been derived from o-ribono-1,4-lactone by a similar strategy. In this case a mild cylopentadienyl mthenium complex was used as catalyst for the cycloaddition step [114]. 

Gabosines which have been isolated from Streptomyces strains constitute a family of keto carbasugars, most of them possessing a trihydroxylated cyclohexenone structure. Because of their interesting bioactivities, a large number of synthetic approaches to these compounds have been proposed (for example [115, 116]). The shortest route (four to five steps) to gabosines I and G was accomplished starting 

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We have been investigating the feasibility of using metathesis to prepare heterocy-elie eompounds such as quinolines and indoles [12] (Scheme 10.5) and its application to the synthesis of bioactive natural products [13],... 

K Mori. Biochemical methods in enantioselective synthesis of bioactive natural products. Synlett 1097-1109, 1995. 

Scheme 3. Synthesis of bioactive natural products via a- and a -C— H transformation oftetrahydrofuran [16,17].

O-Benzylglycidol as a chiral building block in the synthesis of bioactive natural products 91YZ647. 

With the enantioselective intramolecular benzoin reaction established as a synthetic tool, and in combination with our efforts in the synthesis of bioactive natural products bearing a quaternary a-hydroxy ketone unit (Davis and Weismiller 1990 Heller and Tamm 1981), such as the 4-chromanone derivative (S)-eucomol (Bohler and Tamm 1967 Crouch et al. 1999), a catalytic asymmetric synthesis of various 3-hydroxy-4-chromanones brought about by the chiral triazolium salts 127, 123b and 102 as pre-catalysts was investigated (Enders et al. 2006d). The sterically different pre-catalysts were chosen in order to adjust the catalyst system to the steric and electronic properties of the substrates 128. A screening of the reaction conditions indicated 10 mol% of the... 

Richard Taylor obtained BSc and PhD (Dr. D. Neville Jones) from the University of Sheffield. Postdoctoral periods with Dr. Ian Harrison (Syntex, California) and Prof. Franz Sondheimer (University College London) were followed by lectureships at the Open University and then UFA, Norwich. In 1993 he moved to a chair at the University of York. Taylor s research interests center on the synthesis of bioactive natural products and the development of new synthetic methodology. His awards include the Royal Society of Chemistry s Pedlar Lectureship (2007). Taylor is the immediate past-president of the RSC Organic Division and an editor of Tetrahedron. 

Mori, K. Enantioselective Synthesis of Bioactive Natural Products Examples in the Eield of Insect Chemistry, Adv. Asym. Synth., Vol. 1, Hassner, A., Ed., JAEGreenwich, CT, 1995. 

VERSATILE CATALYSTS IN THE SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS... 

I thank my past and present coworkers in chemistry and biology. My thanks are due to Dr. Takuya Tashiro (RIKEN) and my wife Keiko Mori for their help in preparing the illustrations and typing the text, respectively. I am thankful to Shokabo Publisher, Tokyo, for permitting me to use some of the Schemes in my book Seibutsu-Kassei Tennenbutsu no Kagakugosei (Chemical Synthesis of Bioactive Natural Products) published in 1995. 

Natural product chemistry covers a fascinating area of organic chemistry and its study has enriched organic chemistry in a myriad of different ways. In recent years the thrust has been in three major directions advances in stereoselective synthesis of bioactive natural products, developments in structure elucidation of complex natural products through the applications of multidimensional NMR and mass spectroscopy, and the integration of bioassay procedures with the isolation processes leading to the isolation of active principles from the extracts. 

This work was supported by the Direccidn General de Investigacidn Cientifica y Tecnica (DGICYT, Grant PB94-0985). We also thank all the colleagues that share our interest in the chemistry and synthesis of Bioactive Natural Products. 

My research group has been active for nearly 50 years on the synthesis of bioactive natural products of plant, insect, and microbial origins. A brief summary of our work is presented in Figure 3 [2],... 

Advances in iron catalyzed cross coupling reactions, selected applications to the total synthesis of bioactive natural products and pharmaceutically relevant compounds 05CL624. 

A three-step biogenetic-type synthesis of bioactive natural product Luotonin F174 (99H(51)1883) in 38% overall 3deld starts from the natural product pegamine 171 via PCC-oxidation, Friedlander condensation of 172, and chromium trioxide-periodic acid oxidation of 173 (Scheme 34) (02S323). 

Future research endeavors wiU continue in seven-membered heterocycles toward new methods for synthesis of bioactive natural products, apphcation of the mono and diheteroatom systems in medicinal chemistry, and developing new more environment-friendly and economically viable processes for manufacturing drugs. The emerging interest in new metal (e.g., gold, palladium, rhodium, copper, and nickel)-catalyzed processes is expected to continue. 

AppHcations of the treatment of a Co carbonyl-stabilized propargylic cation with nucleophiles to form a new C—C or carbon—heteroatom bond (Nicholas reaction) in the synthesis of natural products 12COC322. Approaches to dihydrooxazine ring systems and application in the synthesis of bioactive natural products 12KGS16. 

Optically active a- and p-hydroxyaldehydes are useful chiral building blocks for the synthesis of bioactive natural products such as grahamimycin Ai [459] and amino sugars [460]. PSL-catalyzed resolution of the corresponding dithioacetal esters gave both enantiomers in excellent optical purity (Scheme 2.65) [461]. A significant selectivity enhancement caused by the bulky sulfur atoms was... 

These reports were the first to describe the use of this type of strategy. The mild reaction conditions and the rapid increase in the structural complexity allowed the synthesis of bioactive natural products in a straightforward way. ... 

Conventional multistep synthesis of natural products reduces the overall yield of the target molecules. In contrast, biomimetic enantioselective domino reactions, promoted by small-molecule artificial enzymes, are more useful for the practical synthesis of natural products and related compounds. The stereoselective formation of polycyclic isoprenoids by the cyclase-induced cyclization of polypren-oids is one of the most remarkable steps in biosynthesis because this reaction results in the formation of several new quaternary and tertiary stereocenters and new rings in a single step. The use of biomimetic polycyclization with artificial cyclase is the most ideal chemical method for the synthesis of these polycyclic terpenoids. In this chapter, biosynthesis of polycyclic terpenoids, biomimetic stereoselective polyene cyclization induced by artificial cyclases, and total synthesis of bioactive natural products using stereoselective polyene cyclization as a key step will be discussed. 

The total synthesis of alkaloid (+)-lycoricidine reported by Yadav et al. represents a further application of the sequence domino reductive fragmentation/allylation followed by ring-closing metathesis in the synthesis of bioactive natural products [42], Thus, reaction of co-iodoglycoside 29 with zinc/allyl bromide in THF/HjO afforded diene 30 (87%, dr 85 15). Ring-closing metathesis of diene 30 followed by acetylation furnished cyclohexene 31. Treatment of the acetate 31 with PhINTs in the presence of Cu(acac)2, followed by sodium naphthalenide, afforded the aziridine 32 (67%), from which (-i-)-lycoricidine (33) can be easily obtained (Scheme 3.11). 

Enzymes and microorganisms help synthetic chemists to prepare nonracemic chiral building blocks. At present lipases are most useful enzymes. Additional new building blocks will be designed and prepared to facilitate enantioselective synthesis. Combination of organic synthesis with biotransformation will continue to provide efficient routes for the enantioselective synthesis of bioactive natural products. 

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