Macrocyclization reactions tether-directed

One of the most convenient of these tether-directed functionalization strategies exploits the macrocyclization of C60 with bismalonate derivatives in a double Bingel reaction.156,571 With the exception of the cis-1 bisaddition product, all possible bisaddition patterns have been obtained by this macrocyclization reaction (Figure 13). As a general... 

Hirsch and co-workers last year introduced a new concept for the tether-directed multifunctionalization of Cgo> with the use of cyclo-[n]-octylmalonates such as 34 (Figure 11) [50], As a result of the identical spacer lengths in these macrocycles, only bis- and tris-adducts with rotational symmetry are formed. The reaction of cyclo-[3]-octylmalonate (34) with Cgo leads to the e,e,e isomer 35 with high regioselectivity and excellent yield (94%). Additionally, 6% of... 

Even tris- and tetrakis-adducts of C6o were accessible in a regioselective way by sequential tether-directed macrocyclization steps. A clipping reaction starting from mono-adduct 40 with two tether-linked malonate residues thus yielded tris-adduct ( )-41 (Scheme 1.5).125 Under the assumption that both m-xylylene tethers enforce the expected cis-2 addition, the C2-symmetry of... 

An enormous range of medically important polyketide and peptide natural products assembled by modular polyketide synthases (PKSs), non-ribosomal peptide synthases (NRPSs) and mixed PKS/NRPS systems have macrocyclic structures, including the antibiotics erythromycin (PKS) and daptomycin (NRPS), the immunosuppressants cyclosporin (NRPS) and rapamycin (PKS/NRPS), and the antitumor agent epothilone (PKS/NRPS). PKSs and NRPSs are large, multifunctional proteins that are organized into sets of fnnc-tional domains termed modules. The order of modules corresponds directly to the seqnence of monomers in the product. Synthetic intermediates are covalently tethered by thioester linkages to a carrier protein domain in each module. The thiol tether on each carrier domain is phosphopantetheine, which is attached to a conserved serine residne in the carrier protein in a post-translational priming reaction catalyzed by a phosphopantetheinyltransferase. 

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