Biological Diels-Alder reaction

Ichihara A., Oikawa H. Biological Diels-Alder Reaction in Biosynthesis of Phytotoxins in Dyn. Aspects Nat. Prod. Chem. 1997 119, Eds. Ogoura K. and Sangawa U., Pb. Kodansha, Tokyo... 

Keywords biological Diels-Alder reaction In biosynthesis of phytotoxins, DIels-Alderase... 

LNKS formally should synthesize a fully elaborated nonaketide such as 47, which could undergo a biological Diels-Alder reaction to form dihydromonacolin L 48—which is the observed hrst PKS-free intermediate. Note that it is possible that the Diels Alder reaction actually occurs at the more activated hexaketide stage. When lovB was expressed in the heterologous fungal host A. nidulans (4) however, the polyunsaturated compounds... 

Cycloaddition, well known as the Diels-Alder reaction, is a widely-used reaction in the synthesis of organic compounds Including natural products. On the other hand, many possible biosynthetic Diels-Alder constructions from natural sources have been reported [1 - 25]. Such constructions in natural are mostly stereo- and regiospecific, suggesting the pivotal step of the cycloaddltlon reaction in the biosynthesis to be enzymatic. However, the evidence for a biological Diels-Alder reaction is rare. 

Biological Diels-Alder reactions are known but uncommon. One example occurs in the biosynthesis of the cholesterol-lowering drug lovastatin (Chapter 1 Introduction) isolated from the bacterium Aspergillus terreus. The key step is the Diels-Alder reaction of a triene in which the diene and dienophile components are within the same molecule. Following this intramolecular Diels-Alder reaction, several subsequent transformations yield lovastatin. 

The photophysical properties of porphycenes make these structures potential sensitizers for an application in Photodynamic Tumor Therapy (PDT). To improve the photophysical properties and to modify possible biological activity it is necessary to have porphycenes with an extended chromophore and/or with additional functional groups for further modifications. The Diels-Alder reaction of a vinyl porphycene allows for the preparation of benzoporphycenes with an extended chromophore9 and additional functional groups (cf. Section 1.1.2.4.). 

The Diels Alder reaction provides a valuable tool for functionalizing buck-minsterfullerene (Ceo)- Functionalized Ceo derivatives may have important applications as conductive materials [45] and in biological chemistry [46]. 

Dihydropyrans [71] and 4-dihydropyranones [72] have been prepared by BF3 or Me2AlCl catalyzed Diels-Alder reactions of alkyl and aryl aldehydes with dienes 72 and 73 (Equations 3.20 and 3.21). Allylic bis-silanes are useful building blocks for synthesizing molecules of biological interest [73], 4-Pyra-nones have been obtained by cerium ammonium nitrate (CAN) oxidation of the cycloadducts. 

Azulene quinones [49b] are compounds related to the family of tropones and are considered to possess great biological and physiological potential. Several polycyclic compounds have been prepared by high pressure (3kbar, PhCl, 130°C, 15h) Diels-Alder reaction of 3-bromo-l,5-azulene quinone (137) and 3-bromo-l,7-azulene quinone (138) with several dienophiles. The cycloadditions were regioselective and afforded cycloadducts in reasonable to good yields (Scheme 5.20). 

Tietze L. F., Modi A. Multicomponent Domino Reactions for the Synthesis of Biologically Active Natural Products and Drugs Med. Res. Rev. 2000 20 304-322 Keywords Diels-Alder reactions... 

Okamura H., Iwagawa M. and Nakatani M. Development of Base Catalyzed Diels-Alder Reaction of 3-Hydroxy-2-Pyrone and Application to Synthesis of Biologically Active Compounds Org. Chem. Japan 1999 57 84... 

Laschat S. Pericyclic Reactions in Biological Systems - Does Nature Know About the Diels-Alder Reaction Angew. Chem., hit. Ed. Engl. 1996 35 289-291... 

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cy-doaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the 1-oxa-l,3-butadiene moiety in 2-816. The formed spirocydic ketones 2-818/2-819 can be used in natural products synthesis and in medidnal chemistry [410]. They have also been used in the preparation of exotic amino adds these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

Stocking, E.M., and Williams, R.M. (2002) Chemistry and biology of biosynthetic Diels-Alder reactions. Angew. Chem. Int. Ed. Engl. 42(27), 3078-3115. 

An intramolecular cycloaddition also occurred with 3-ylidenepiperazine-2,5-diones such as 124 or 125, obtained by Wittig-Horner-Emmons reaction from phosphonate 121 and aldehydes 122 or 123, respectively. The products of the Diels-Alder reaction are the bridged bicyclo[2.2.2]diazaoctane rings 126 and 127 that have been found in biologically active secondary metabolite such as VM55599 and brevianamide A. The different type of structures employed in this case requires a chemoselective reaction in order to produce the expected products as single diastereoisomers after 20 days (Scheme 18) <2001JOC3984>. 

The use of porphyrinic ligands in polymeric systems allows their unique physio-chemical features to be integrated into two (2D)- or three-dimensional (3D) structures. As such, porphyrin or pc macrocycles have been extensively used to prepare polymers, usually via a radical polymerization reaction (85,86) and more recently via iterative Diels-Alder reactions (87-89). The resulting polymers have interesting materials and biological applications. For example, certain pc-based polymers have higher intrinsic conductivities and better catalytic activity than their parent monomers (90-92). The first example of a /jz-based polymer was reported in 1999 by Montalban et al. (36). These polymers were prepared by a ROMP of a norbor-nadiene substituted pz (Scheme 7, 34). This pz was the first example of polymerization of a porphyrinic macrocycle by a ROMP reaction, and it represents a new general route for the synthesis of polymeric porphyrinic-type macrocycles. 

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