High Level Quantum-Chemical Computations on the Cyclizations of Enyne Allenes

Matthias Prall and Peter R. Schreiner
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Matthias Prall: Georg-August-University, Institute of Organic Chemistry
Peter R. Schreiner: Georg-August-University, Institute of Organic Chemistry

A chapter in High Performance Computing in Science and Engineering ’99, 2000, pp 194-211 from Springer

Abstract: Abstract The ring-closure reactions of the enediyne and enyne-allene moieties of the natural antitumor antibiotics neocarzinostatin (1), calicheamicin (4), and dynemicin (5) are held responsible for the DNA-cleavage abilities of these potent pharmacophors. Neocarzinostatin, first isolated from Streptomyces carzinostaticus in 1961 [1], consists of the key chromophore 1 (Fig. 1.1) bound to a 113-amino acid apoprotein. [2,3] The enediyne moiety of 1 is activated by a thiol nucleophile, rearranges to enyne-cumulene 2, and cyclizes to the highly reactive biradical 3 (Fig. 1.1), a reaction akin to the Myers-Saito cyclization. [4] Since 1 binds to the minor groove of DNA, [5–;7] 3 is able to abstract hydrogens from adenine or thymine moieties [8] leading to cell damage. While calicheamicin 4 and dynemicin 5 (Fig. 1.1) undergo Bergman cyclizations to give rise to 1,4-didehydrobenzene biradicals, the neocarzinostatin chromophore 1 reacts differently.

Keywords: Spin Density; American Chemical Society; Cyclization Reaction; Reaction Enthalpy; Cyclization Product (search for similar items in EconPapers)
Date: 2000
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DOI: 10.1007/978-3-642-59686-5_17

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