Danishefskys Total Synthesis of Dynemicin

in the first operation, 31 was treated with ceric ammonium nitrate (CAN) in aqueous MeCN to effect the oxidative conversion of its C-ring into a quinone, an event attended by the concomitant scission of its B-ring to afford a hydroxymethyl function in the product (30). However, since a residual aldehyde from the Diels- Alder reaction was present on the same side of the A-ring as this newly generated alcohol, the isolated product was not 30, but instead was lactol 74. Although this latter ring closure was not critical for the operations ultimately needed to reach 28, it did serve to protect the oxidized substrate (30) from the action of excess CAN. For example, only decomposition resulted when the exo Diels—Alder variant of 31 was subjected to the same conditions, presumably because the hydroxymethyl function that was produced in this case could not form a lactol since its aldehyde partner was on the opposite side of the molecule. 

Unfortunately, initial probes of Sonogashira-type reactions on substrates related to 80 led to no material in which the enediyne bridge had been fashioned, suggesting that perfiaps the terminal alkynes possessed too poor a conformational disposition for the 

5 Schreiber s Synthesis of Tri-O-Methyl Dynemicin A Methyl Ester 

For other papers related to the mode of activity of dynemicin A, see the foUowing (and references cited therein) a) Y. Sugiura, T. Shiraki, M. Konishi, T. Oki, Proc. Natl. Acad, Sci. U.S.A 1990, 87, 3831  

For an excellent review on the Diels—Alder reactions of isobenzofiirans, see R. Rodrigo, Tetrahedron 1S 88, 44, 2093. For the first example of this diene in a natural product total synthesis, see A. S. Kende, D.P Curran, Y. Tsay, J.E. Mills, Tetrahedron Lett. 1977, 18, 3537. 

---