| In recent years, a large number of cycloisidityrosine-derived natural products including the antibiotic piperazinomycin and the potent antitumor antibiotics bouvardin, deoxybouvardin and the RA series of bicyclic hexapeptides have been discovered. Their novel structures, unusual conformational features and impressive biological properties have elicited extensive research efforts including those directed at their total synthesis. The 14-membered cycloisidityrosine segment of these natural products has proven to he fundamentally important to their biological properties. The challenge for the synthesis of these naturally occurring agents lies in the construction of the 14-membered cycloisodityrosine subunit. Herein, the efforts on the synthesis of cycloisodityrosine-derived natural products are described. A concise total synthesis of (+)-piperazinomycin is detailed based on the implementation of an improved Ullmann macrocyclization reaction conducted on a diketopiperazine. The asymmetric synthesis of N-methyl erythro-;During the last decade, extensive studies on CC-1065, the initial member of a class of exceptionally potent antitumor antibiotics now including the duocarmycins, have resulted in two distinct proposals for the origin of the DNA alkylation selectivity. One proposal attributes the selectivity to kinetic reactivity at the preferred alkylation sites and the other suggests the preferential noncovalent binding selectivity restricts the accessible sites of DNA alkylation. Herein, the linkage of CDPI... |
