Nine neocarzinostatin chromophore

While these model studies have shed light on the natnre of the Myers-Saito and Schmittel cycUzations, the molecules examined bear important differences from the neocarzinostatin chromophore the chromophore is a bntadiene not an aUene the enyne-butatriene is embedded within a nine-member ring this ring is fnsed with a cyclopentane moiety and the ring bears an alcohol substitnent. 

Martin s sulfurane has been used to prepare a variety of cyclopentenes for use in the total syntheses of complex natural products. Myers effectively employed the title reagent to prepare synthetic intermediates for use in his total synthesis of the neocarzinostatin chromophore.43 (For dehydrations to yield alkenes in the nine-membered ring of this compound, see Section 3.7.5.4.) One example is reaction of tertiary alcohol 86 to furnish alkene 87 in 93% yield. In Phillips s total synthesis of cylindramide A, he employed a conjugate addition-reduction-elimination sequence (88—>89) to generate the... 

Neocarzinostatin 301, first reported by Ishida and coworkers in 1965, is produced by S. carzinostaticus ATCC 15994 and is a 1 1 noncovalently associated mixture of a protein component, apoprotein, and a chromophoric molecule [297]. The mixture was separated somewhat later into its component parts and eventually characterized structurally. The chromophoric component was shown in 1985 to have the nine-membered polyeneyne skeleton 301 [298]. The apoprotein has been characterized as a 113 amino acid polypeptide based upon the gene base sequence and apoprotein crystal structure [299, 300]. The three-dimensional solution structure of intact neocarzinostatin was determined using 2D NMR techniques [301], and the crystal structure of holo-neocarzinostatin was reported in the same year [302]. The antibiotic 301 showed potent antitumor activity against a wide range of tumors and a poly(styrene-co-maleic acid)-301 conjugate was approved in Japan and has been marketed for use against hepatoma since 1994 [303]. 

Figure 3.1 Nine-membered enediyne chromophores whose structures have been elucidated neocarzinostatin (3.405), kedarcidin (3.406), C-1027 (3.407), maduropeptin (3.408), and N1999A2 (3.409).

---