TOTAL SYNTHESIS OF RACEMIC AND OPTICALLY-ACTIVE SARKOMYCIN

trans-3-Carboxy-2-diethoxyphosphorylcyclopentanone (11), a key precurs or of sarkomycin 1, has been synthesized in the rhodium(II) acetate pr omoted cyclization of diethyl 1-diazo-2-oxohept-6-enephosphonate (9), followed by transformation of the 3-vinyl moiety into the 3-carboxylic group. Racemic 11 has been resolved into enantiomers via diastereoiso meric enamine-type derivatives 13 resulting from its reaction with (-) -(S)-1-(1-naphthyl)ethylamine. The structure and absolute configuratio n of 13 have been determined by X-ray crystal structure analysis. The enantiomerically enriched (up to 77.6% ee) acid 11 has also been obtai ned in the enzyme-promoted hydrolysis of racemic diethoxyphosphoryl-3- methoxycarbonylcyclopentanone (12). The Horner-Wittig reaction of 11 w ith gaseous formaldehyde has been applied to introduce the exocyclic a lpha-methylene moiety into the cyclopentanone system and thus to compl ete the synthesis of the racemate and, for the first time, each enanti omer of sarkomycin 1. A phenomenon of enantiomer self-discrimination h as been observed in P-31 NMR spectra of the nonracemic acid 11 and exp lained in terms of the formation of the hydrogen bonded homo- and hete ro-dimers. The existence of dimeric structures has been confirmed by X -ray analysis of the structurally closely related ans-3-carboxy-2-diph enylphosphinoyl-cyclopentanone (16).