A BUTYROLACTONE-]1,3-DIOL STRATEGY FOR THE OBTENTION OF TOLYPOTHRIX POLYETHERS - STEREOSELECTIVE SYNTHESIS OF A KEY LACTONE PRECURSOR

A novel access to 1,3,5,7,...-polyols is developed. It follows - in th e context of the planned synthesis of the natural permethylated 1,3,5, 7,9-pentaol la from the blue-green alga Tolypothrix conglutinata - the strategy depicted in Scheme 4. The present paper concerns the enantio selective synthesis of the key building block syn-ga. This gamma-lacto ne was derived from O-tert-butyldiphenylsilylglycidol (R-15) via a syn thetic equivalent of the 6-hydroxy-4-ketoester 12 (cf. Scheme 5). As s uch, we used the hydroxydiene 28 rather than the 2-(5-hydroxy-3-methyl enepentyl)-1,3-oxazoline 26 or the (5-hydroxy-3-methylenepentyl)-subst ituted orthoester 27 because of its greater ease of preparation (cf. S cheme 7). A double ozonolysis of the hydroxydiene 28 provided the desi red 6-hydroxy-4-ketoester 12 itself (Scheme 8). The C=O bond of this c ompound was reduced syn-selectively (ds = 100:0) through successive ad ditions of Et2B(OMe) and NaBH4 and anti-selectively (ds = 80:20) throu gh the addition of NaB-H(OAc)(3) (Scheme 9). The dihydroxy ester syn-3 4 formed in the mentioned syn-selective reduction was isolable or coul d be lactonized in the presence of acid so that the syn-configured hyd roxy lactone syn-ga was obtained directly (Scheme 10).