Tri-O-methyl dynemicin

Schreiber et al. have been able to apply their enediyne intramolecular Diels-Alder approach to the synthesis of dynemicin model systems [268-270], culminating in the total synthesis of di- and tri-O-methyl dynemicin A methyl esters 388 and 389 (Scheme 7-78) [271], derivatives of the natural product itself. Highlights of this synthetic approach include (a) intramolecular lactonization and concomitant Diels-Alder cyclization (380- 381) (b) allylic hydroxylation followed by an allylic diazene rearrangement in order to regiospecifically isomerize a double bond (381 - 382) (c) a-hydroxylation of the lactone 381 and subsequent conversion to the P-ketoester 383 (d) annelation of the anthraquinone unit (383- 384- 385- 386) (e) mild base-induced P-elimination of the N-protecting group of 386 to give the free amine 387 and (f) a final oxidation to complete the anthraquinone (387 - 388). 

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

Scheme 16. Schreiber s synthesis of tri-O-methyl dynemicin A methyl ester (107).

Benzyloxypropyl chloroformate 106, a useful reagent in the total synthesis of di-and tri-O-methyl Dynemicin A methyl esters, was prepared by syringe pump addition (over 2 h) of 3-benzyloxypropanol 105 (2.9 equiv.) and pyridine (3.0 equiv.) to a solution of triphosgene in dichloromethane at 0 °C [59]. 

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