Calichemicins

Bicyclic Core of the Esperamicin/Calichemicin Class of Antitumor Agents... 

Lee MD, Dunne TS, Siegel MM, Chang CC, Morton GO, Borders DB. (1987) Calichemicins, a novel family of antitumor antibiotics. 1. Chemistry and partial structure of calichemicin yll. J Am Chem Soc 109 3464-3466. 

Nagata, R. Yamanaka, H. Okazaki, E. Saito, I. Biradical formation from acyclic conjugated eneyne-allene system related to neocarzinostatin and esperamicin-calichemicin, Tetrahedron Lett. 1989, 30,4995-4998. 

Myers, A.G. Kuo, E.Y. Finney, N.S. Thermal generation of alpha,3-dehydrotoluene from (Z)-l,2,4-heptatricn-6-ync. J. Am. Chem. Soc. 1989, 111, 8057-8058 Nagata, R. Yamanaka, H. Okazaki, E. Saito, I. Biradical formation from acyclic conjugated eneyne-allene system related to neocarzinostatin and esperamicin-calichemicin. Tetrahedron Lett. 1989, 30, 4995 998. 

Calf intestinal alkaline phosphatase, see clAP Calichemicin 1125 Calmette-guerin vaccine 1430 Calnexin 420, 427 Calogen 477... 

Aryl iodides, bromides, and inflates are used for Sonogashira coupling. But so far few smooth reactions of aryl chlorides with alkynes have been reported. On the other hand, smooth coupling takes place with alkenyl chlorides. The Pd-catalyzed reaction of 1-alkynes with alkenyl chlorides, which are inert in many other Pd-catalyzed reactions, proceeds smoothly without special activation of the chlorides. For example, cw-l,2-dichloroethylene (31) can be coupled with 1-alkynes smoothly, and the coupling has wide synthetic applications, particularly for the synthesis of enediyne structures [30]. The reaction of 31 with two different 1-alkynes is extensively used for construction of highly strained enediyne structures present in naturally occurring anticancer antibiotics such as espermicin and calichemicin [31,32]. The asymmetric (Z)-enediyne 34 can be prepared by a one-pot reaction of 31 with two different 1-alkynes 32 and 33. Similarly the asymmetric ( )-enediyne 37 was obtained in a one-pot reaction of 1-alkynes 33 and 23 with 1,2-dichloroethylene 35. 

The challenge of the synthesis of the ene-diyene natural products was one of the factors that brought the Sonogashira reaction to prominence. Three Sonogashira reactions were used in a synthesis of the core of the esperamycin/calichemicin anti-tumour agents (Scheme 2.117). Two were employed in sequence to add two alkynes onto cw-l,2-dichloroethylene 2375 to form the ene-diyne 2376. Due to the sensitivity of propiolaldehyde, its diethyl acetal was employed. After hydrolysis of the acetal, a diene unit was installed. 

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