Ten-membered enediyne

Usuki T, Nakanishi K, Ellestad GA (2006) Spin-Trapping of the p-Benzyne Intermediates from Ten-Membered Enediyne Calicheamicin yi . Org Lett 8 5461... 

Wender et al. have also synthesized dynemicin A model systems (Scheme 7-76). In this approach, closure of the ten-membered enediyne ring was achieved by fluoride-induced de-silylative condensation of a silyl-protected alkyne with an aldehyde (365 - 366) [262]. Following the example of Nicolaou et al., these researchers have also deplored simulation of the... 

The stractural and functional relatedness of SgcE and CalES suggested a common polyketide pathway for the biosynthesis of both nine and ten-membered enediynes, despite the fact that their incorporation patterns by Relabeled acetate feeding experiments were distinct. The two carbons that make up each triple bond of neocarzinostatin and C-1027 (both nine-membered enediynes) are derived from intact acetate units, whereas those of cahcheamicin are known to be derived from adjacent acetate units. Like SgcE, the CalES PKS could be envisioned to produce a nascent polyunsaturated intermediate from... 

Beginning in the 1980s research directed toward the isolation of new drugs derived from natural sources identified a family of tumor inhibitory antibiotic substances characterized by novel struc tures containing a C C—C=C—C C unit as part of a nine or ten membered ring With one double bond and two triple bonds (-ene + di- + -yne) these com pounds soon became known as enediyne antibiotics The simplest member of the class is dynemian A most of the other enediynes have even more compli cated structures... 

Enediyne antibiotics (Section 9 4) A family of tumor inhibit mg substances that is characterized by the presence of a C=C—C=C—C = C unit as part of a nine or ten membered nng... 

Of great importance for the Bergman cyclization is the distance between the triple bonds. The reaction cannot occur at moderate temperatures if the distance is too large. Optimal reactivity at physiological temperatures is obtained by fitting the enediyne element into a ten-membered ring." ... 

Nicolaou, K.C. Sorensen, E.J. Discordia, R. Hwang, C.-K. Minto, R,E, Bharucha, K.N. Bergman, R.E. Ten-membered ring enediynes with remarkable chemical and biological profiles. Angew. Chem., Int. Ed. Engl. 1992, 31, 1044-1046. 

There are only a few naturally occurring alkynes. Examples include capillin, which has fungicidal activity, and ichthyothereol, a convulsant used by the Amazon Indians for poisoned arrowheads. A class of naturally occurring compounds called enediynes has been found to have powerful antibiotic and anticancer properties. These compounds all have a nine- or ten-membered ring that contains two triple bonds separated by a double bond. Some enediynes are currently in clinical trials. 

The intramolecular variant of this synthesis renders cyclic enediynes. Ten-membered functionalized enediyne cycles (7) were generated in yields of up to 95 % using slightly altered reaction conditions. Since the starting materials are easily accessible, a synthesis of enediynes in multigramm scale can be achieved. Thus, it should be possible to use those functionalized enediyne components to build libraries of enediyne diversomers, by the approach of Nicolaou and others. [11] Ene-diyne-steroide conjugates, like 8, and ene-... 

While most attention has been directed towards the preparation of carbocyclic enediynes, ten-membered heterocyclic enediynes... 

A mixture of the ten-membered cyclic cw-diol 648 and its trans- om v is obtained from the enediyne dialdehyde 647. A new family of hydrocarbon rings, the three skipped cyclic C12H12 dienediynes 649 - 651, has been described. These compounds were prepared from dilithium derivatives of enediynes and diiodo- or dibromoalkenes as shown in Scheme 6. Treatment of 651 with CpCo(CO)2 gave the cobalt sandwich complex 652 ". ... 

Cultures of the bacterium Micromonospora chersina produce dynemicin A, a novel substance containing a double bond and two triple bonds in a ten-membered ring (an enediyne). Dynemicin A has attracted interest because of its unusual structure as well as its interesting biological activity. It has the ability to cleave DNA by a novel mechanism, which may lead to the development of anticancer drugs that are based on the enediyne structure. 

The biosynthesis of the enediyne core of calicheamicin and other similar compounds (both nine- and ten-membered) involve a common enediyne polyketide synthase (named PKSE) [295,... 

Enediynes 3.798 also with a fused p-lactam ring but now with the nitrogen atom as part of the ten membered ring [218, 220] were synthesized by carbene insertion in diazo enediyne 3.797 in 50% yield (Scheme 3.97) [26, 369-371]. This was prepared by acylation of amine 3.795 with ethyl malonyl chloride in the presence of triethylamine to give amide 3.796, followed by the treatment with p-toluene sulfonyl azide on potassium carbonate as solid support. Treatment of solution of the diazo enediyne product 3.797 with a catalytic amount of rhodium acetate for 30 minutes resulted in the lactam-fused enediyne as the only isolable product. 

Strained ten-membered enediynyl system 3.853 which would be formed in the case of the 13-membered ring of enediyne 3.852. 

---