Stereoselective routes to cyclic β-amino acid derivatives

Abstract

The literature structure of the natural product oryzoxymycin and an array of 3-mono-,3,4-di- and 3,4,5-tri-hydroxylated derivatives of 2-aminocyclohexane-l-carboxyhc acid (ACHC) were stereoselectively prepared from oxanorbomene adducts derived from the Diels Alder reaction of ethyl (E)-3-nitroacrylate and furan. The central reaction for these syntheses was the base mediated β-elimination of the oxygen bridge of the oxanorbomene adducts or their derivatives. The asymmetnc synthesis of the literature structure of oryzoxymycin involved chiral HPLC or enzyme catalysed kinetic resolution of the endo-carbamate oxanorbornene adduct. KHMDS promoted β-elimination of the oxygen bridge of the optical pure adduct afforded a 5,6-dihydro-5-hydroxyanthranilate which was converted to oryzoxymycin through CsF mediated coupling to a lactate and deprotection. Alternatively, the double bonds of the dihydrohydroxyanthranilates were stereoselectively reduced to give the 3-hydroxylated ACHC derivatives. The di- and trihydroxylated ACHC derivatives were prepared from the oxanorbomene adducts through selective oxidation sequences that took advantage of substrate stereocontrolled processes. The oxidation reactions which feature in the synthesis of the polyhydroxylated ACHC derivatives were epoxidation and O(_s)O(_4) catalysed dihydroxylation. The structures of intermediates and final products were characterised by NMR, IR and MS. The X-ray-structures of the crystalline compounds were also recorded.