Synthesis Synthetic strategies

Di- and trinucleotides may be used as units instead of the monomers. This convergent synthetic strategy simplifies the purification of products, since they are differentiated by a much higher jump in molecular mass and functionality from the educls than in monomer additions, and it raises the yield. We can illustrate the latter effect with an imaginary sequence of seven synthetic steps, c.g. nucleotide condensations, where the yield is 80% in each step. In a converging seven-step synthesis an octanucleotide would be obtained in 0.8 x 100 = 51% yield, compared with a 0.8 x 100 = 21% yield in a linear synthesis. 

Another synthetic strategy is based on self-assembly driven by molecular recognition between complementary TT-donors and 7T-acceptors. Examples include the synthesis of catenanes and rotaxanes that can act as controUable molecular shuttles (6,236). The TT-donors in the shuttles are located in the dumb-beU shaped component of the rotaxane and the 7T-acceptors in the macrocycHc component, or vice versa. The shuttles may be switched by chemical, electrochemical, or photochemical means. 

Chemical Modification. The chemistry and synthetic strategies used in the commercial synthesis of cephalosporins have been reviewed (87) and can be broadly divided into ( /) Selection of starting material penicillin precursors must be rearranged to the cephalosporin nucleus (2) cleavage of the acyl side chain of the precursor (2) synthesis of the C-7 and C-3 side-chain precursors (4) acylation of the C-7 amino function to introduce the desked acylamino side chain (5) kitroduction of the C-3 substituent and 6) protection and/or activation of functional groups that may be requked. 

Utilization of carbenes in the synthesis of five-membered heterocycles with two or more heteroatoms has not been featured prominently in the synthetic strategies developed for these ring systems. The following illustrations show their considerable promise. 

Early attempts to apply the Sheehan penicillin synthetic strategy to the total synthesis of cephalosporins were not particularly successful. Although the key step, formation of the /3-lactam CO—N bond, could be carried out efficiently (46->47), subsequent conversion of the lactone to a free C-4 carboxyl could only be accomplished in poor yield (B-72MI51007). 

Synthesis of cryptands which contain nitrogen atoms in the bridges has also attracted Lehn s attention. In general, a similar synthetic strategy was utilized, but ni-... 

The synthetic strategy towards the copolymers is shown in Figure 16-3. The use of bifunctional monomers in a Heck reaction allows the synthesis of polymers, and the great potential of this approach has been demonstrated previously [53-55]. The syntheses have been described in detail by Hilberer el al. [16],... 

The homology of the tricyclic products in Scheme 6 to the ABC-ring portion of the steroid nucleus is obvious. In fact, the facility with which these tricyclic materials can be constructed from simple building blocks provided the impetus for the development of an exceedingly efficient synthesis of the female sex hormone, estrone (1). This important biomolecule has stimulated the development of numerous synthetic strategies and these have been amply reviewed.16 The remainder of this chapter is devoted to the brilliant synthesis of racemic estrone by K. P. C. Vollhardt et al.i2 17... 

Several elegant synthetic strategies have been devised for biotin (1) this chapter describes one of the total syntheses developed at Hoffmann-La Roche. This insightful synthesis employs a derivative of L-cysteine, a readily available member of the chiral pool,2 as the starting material, and showcases the powerful intramolecular nitrone-olefin [3+2] cycloaddition reaction. 

On the basis of the examples addressed thus far, it is clear that radical reactions can accomplish manifold transformations in organic synthesis. One of the outstanding achievements of synthetic radical chemistry is the development of synthetic strategies based on controlled, tandem radical cyclizations. The efficiency of such strategies is exemplified in the substantial and elegant synthetic work of D. P. Curran and his group.54 The remainder of this chapter will address the concise total syntheses of ( )-hirsutene [( )-1]55 and ( )-A9(12)-capnellene [( )-2]56 by the Curran group. 

Although one of the two building blocks has to be symmetric to avoid constitutional isomers, the symmetry constraints differ from those of the 2 + 2 approach and this allows the synthesis of structures that would be difficult to obtain by other synthetic strategies. Consequently, the 3 + 1 strategy has been accepted and is an increasingly used method for porphyrin synthesis.49... 

A similar synthetic strategy was applied in the synthesis of menogaril 83, another important anthracycline antitumour antibiotic, and to the synthesis of the tricyclic core of olivin 87, the aglycon of the antitumour antibiotic olivomycin [61,62]. In both cases a tandem benzannulation/Friedel-Crafts cyclisation sequence yielded the tetracyclic and tricyclic carbon core, respectively (Scheme 42). 

Based on this synthetic strategy an efficient method for the synthesis of 2,3-dihydro- 1,2-benzisoxazoles 137 and indazoles was elaborated [77a] (Scheme 57). 

In most cases, the overall synthesis time was greatly reduced (from hours or days to minutes) by switching from conventional to microwave heating, facilitating the rapid preparation of novel chemical entities. The combination of soUd-phase synthesis with microwave irradiation also allowed access to a few classes of molecules that had proven elusive via other synthetic strategies (traditional solution-phase synthesis). 

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