Calicheamicin-Dynemicin

In a synthesis of a Calicheamicin-Dynemicin hybrid, Nicolaou and co-workers209 removed an Fmoc group in the presence of the base-sensitive 2-(phenylsulfonyl)-... 

Nicolaou, K C, Schreiner, E P, Iwabuchi, Y, Suzuki, T, Total synthesis of calicheamicin dynemicin hybrid molecules, Angew. Chem. Int. Ed. Engl, 31, 340-342, 1992. 

Figure 1. Naturally occurring enediynes and natural products for which enediynes have been proposed as biosynthetic intermediates, (a) The 10-memberedfamily includes calicheamicin, dynemicin, esperamicin, shishijimicin, namenamicin, and uncialamycin. (b) The 9-membered enediynes include neocarzinostatin (NCS), C-1027, maduropeptin, kedarcidin, andN1999A2. (c) Sporolides A and B and cyanosporasides A and B are all hypothesized to originate from enediyne precursors (bracketed) based on the presence of the enediyne polyketide synthase (PKSE) in the Salinaspora genome of each producing organism.

Several novel natural products with an intriguing system containing the cis-endiyne moiety have attracted considerable attention from chemists in recent years. Several derivatives with this characteristic skeleton have now been isolated neocarzinostatin,96 esperamicin,97 calicheamicin y. 9S and dynemicin Ai." The high antitumor activity of these compounds is based on an elegant... 

The family of enediynes includes the calicheamicins, esperamycins, dynemicin A, which is not glycosylated, the C-1027 chromophore and kedarcidin (O Fig. 18 and Fig. 19). The neocarzinostatin chromophore, which does not contain an (Z)-enediyne, is also included in this family of compounds because of a similar mode of action. 

A dynemicin A analog resembling also the calicheamicin structure has been synthesized by Magnus et al. In this case the epoxide is not present and the role of safety catch is played by the carbonyl on the shortest bridge. The synthesis of 101 (Scheme 19.27) is achieved exploiting the reaction... 

Danishefsky, S. Shair, M.D. Observations in the chemistry and biology of cyclic enediyne antibiotics Total syntheses of calicheamicin y/ and dynemicin A. J. Org. Chem. 1996, 61, 16-44. 

Once the structures of the first natural enediyne antibiotics had been elucidated, the scientific community was quick to respond. The mechanisms by which these molecules exert their effects continue to be probed ever deeper, with surprising new details still emerging. The hitherto unprecedented and structurally complex molecular architecture of the natural products has required the development of new synthetic methodology in order to synthesize functional models which would shed new light upon the natural enediyne antibiotics. Researchers in the field have pushed the art of organic synthesis to its present limits with total syntheses of calicheamicin yj (2), the most prominent member of the natural enediyne antibiotics, and a derivative of dynemicin A (4) having been achieved. Furthermore, the factors affecting the... 

When the structure of dynemicin A (4) was revealed in 1989 [24, 25], the combination of its intriguing novelty, potent antitumor and antibiotic properties, and low toxicity by comparison with other enediyne antibiotics such as calicheamicin yj (2) were sufficient to ensure the attention of a scientific community already fascinated by its forebears. 

Kedarcidin. A further enediyne antibiotic with antitumor activity besides the calicheamicins, espera-mycins, dynemicins, and neocarzinostatins. 

The endiyne and enyne-allene have attracted the attention, as they undergo facile cycloaromatization to produce reactive biradicals [1], which could mimic the DNA-cleaving mechanism and properties of the new class of very potent antitumor antibiotics calicheamicins [2], esperamicins [3], neocarzinostatin [4], and dynemicins [5]. 

Figure 3.2 Structures of 10-membered enediynes calicheamicin (3.412), namenam-icin (3.413), shishijimicin (3.414), esperamicin (3.415), and dynemicin (3.416).

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