Total Synthesis of Racemic and Optically Active Sarkomycin

Marian Mikoajczyk; Remigiusz urawiski; Piotr Kiebasiski; Micha W. Wieczorek; Jarosaw Baszczyk; Wiesaw R. Majzner

doi:10.1055/s-1997-1193

Synthesis 1997; 1997(3): 356-365
DOI: 10.1055/s-1997-1193

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Total Synthesis of Racemic and Optically Active Sarkomycin

Marian Mikołajczyk¹ , Remigiusz Żurawiński² , Piotr Kiełbasiński² , Michał W. Wieczorek³ , Jarosław Błaszczyk³ , Wiesław R. Majzner³

¹Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, PL-90-363 Łódź, Sienkiewicza 112, Poland, Fax +48(42)847126
²Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, PL-90-363 Łódź, Sienkiewicza 112, Poland
³Institute of General Food Chemistry, Technical University of Łódź, PL-90-924 Łódź, Stefanowskiego 4/10, Poland

Abstract

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trans-3-Carboxy-2-diethoxyphosphorylcyclopentanone (11), a key precursor of sarkomycin 1, has been synthesized in the rhodium(II) acetate promoted 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 diastereoisomeric enamine-type derivatives 13 resulting from its reaction with (-)-(S)-1-(1-naphthyl)ethylamine. The structure and absolute configuration of 13 have been determined by X-ray crystal structure analysis. The enantiomerically enriched (up to 77.6% ee) acid 11 has also been obtained in the enzyme-promoted hydrolysis of racemic 2-diethyoxyphosphoryl-3-methoxycarbonylcyclopentanone (12). The Horner-Wittig reaction of 11 with gaseous formaldehyde has been applied to introduce the exocyclic α-methylene moiety into the cyclopentanone system and thus to complete the synthesis of the racemate and, for the first time, each enantiomer of sarkomycin 1. A phenomenon of enantiomer self-discrimination has been observed in ³¹PNMR spectra of the nonracemic acid 11 and explained in terms of the formation of the hydrogen bonded homo- and hetero-dimers. The existence of dimeric structures has been confirmed by X-ray analysis of the structurally closely related trans-3-carboxy-2-diphenylphosphinoyl-cyclopentanone (16).

sarkomycin - resolution - enantiomer self-discrimination - enzymatic hydrolysis

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