Synthesis of Biologically Active Molecules

Stoichiometric palladium-mediated cyclization was used in natural product synthesis by Boger a number of years ago, as was noted in the introduction. More recently, an intramolecular palladium-catalyzed amination of a heteroaromatic halide has been used as a step in the synthesis of an a-carboline natural product analog [146]. As discussed above, the diphenylhydrazone arylation can also be used for nitrogen heterocycle synthesis [140]. 

---

Abstract A -Heterocyclic carbene complexes produced on industrial scale are presented in this chapter along with a discussion about their production. Details of processes employing NHC complexes on pilot to industrial scales are discussed. These are frequently oriented towards the synthesis of biologically active molecules, however, examples are given for rubber formation and for 1-octene synthesis, a comonomer for polyethylene synthesis. 

He is an author of more than 150 papers published in international scientific journals. His scientific interests cover the synthesis of biologically active molecules and the development of new methodologies directed to synthesis automation applied to drug discovery and drug optimization. 

The principal classes of reported heterogeneously catalyzed reactions and the synthesis of biologically active molecules by heterogeneous diastereoselective catalysis are covered in a recent review by De Vos and coworkers [86],... 

Without doubt, multicomponent reactions have become an attractive tool for the synthesis of biologically active molecules. In this regard, Jeong et al. reported an interesting domino synthesis of bicyclopentenones [50]. They employed a bimetallic system consisting of [Pd2(dba)3(CHCl3)] and... 

Automated PASP Synthesis of Biologically Active Molecules... 

Selective alkylation of 1,2,4-triazole in position 1 is of primary interest for the synthesis of biologically active molecules such as fungicides (fluconazole, flutriafole,... 

Catalytic asymmetric synthesis of biologically active molecules 07Y439. 

A number of groups have investigated the Pd-catalyzed amination of aromatic electrophiles for a particular application or synthetic problem. These synthetic applications can be divided loosely into four categories synthesis of biologically active molecules, synthesis of materials for electronics or ion binding, amination in solid-phase organic synthesis, and synthesis of new ligands for transition metals. 

The asymmetric oxidation of sulfides represents a straightforward access to chiral sulfoxides that are useful compounds for asymmetric synthesis as chiral auxiliaries and also for the synthesis of biologically active molecules. Among the different methods to perform these reactions, titanium-mediated thioether oxidation is one of the most attractive. Indeed, Kagan ° and Modena independently showed that the use of chiral titanium complexes derived from Sharpless reagent allows the asymmetric oxidation of prochiral sulfides (Scheme 7.6). 

It is worth noting that the Shibasaki group also developed a highly useful protocol for asymmetric Mannich-tyip reactions (556), which was used successfully in the synthesis of biologically active molecules like nemonapride, an antipsychotic agent developed by Yamanouchi Pharmaceutical. Since such a useful application of this methodology is not a bom fide natural product synthesis, a detailed discussion is beyond the scope of this contribution and the interested reader is referred to Shibasaki s original report (556). 

The development of new strategies in organic synthesis with a minimum of chemical steps has become more and more necessary for the efficient creation of complex molecular structures. The ability of palladium(O) catalysts to exercise control in bond forming has made it an excellent candidate for the synthesis of biologically active molecules. Allylic alkylations catalyzed by palladium have widely been studied and have proved unusually productive because of the extraordinary chemo-, regio-, and diastereoselectivity and the continuing possibility for the development of enantioselectivity. 

The chemo- and regioselectivity problems can be solved by the [2+2+2] cycloaddition of diynes with monoynes, although the accessible products are limited to bicyclic compounds. The [2+2+2] cycloaddition of diynes with monoynes has been applied to the synthesis of biologically active molecules and functional materials. The first application in the natural product synthesis was the dl-estrone synthesis using CpCo(CO)j as a catalyst. The [2+2+2] cycloaddition followed by the benzocyclobutane to ort/jo-quinodimethane rearrangement and intramolecular Diels-Alder reaction afforded a dZ-estrone precursor (Scheme 21.8) [11]. 

In this last section, the focus shifts to intermolecular palladium-catalyzed MBFTs that are exploited for the synthesis of biologically active molecules. There are several reasons why palladium is one of the most widely employed transition metals. First, it allows facile oxidative insertion and reductive elimination. Second, palladium accepts a broad range of functional groups and its reactivity is heavily influenced by the addition of ligands. Last, by creating asymmetric catalytic complexes, stereoselective reactions are facilitated. Nevertheless, the metal is not commonly used in MBFTs for the synthesis of products that are tested for biologically activity. Therefore, only a few examples will be discussed which provide products that are currently exploited for their biological effect. 

Since the initial eonmiunication by Suzuki and coworkers, the Suzuki reaction has evolved into one of the most commonly used methods for the construction of C-C bonds. The Suzuki reaction has found many applications in the synthesis of biologically active molecules and useful materials. The reactions are amenable to scale-up, and are broadly employed in the pharmaceutical industry. ... 

---