A BUTYROLACTONE-]1,3-DIOL STRATEGY FOR THE OBTENTION OF TOLYPOTHRIX POLYETHERS - TOTAL SYNTHESIS OF THE TOLYPOTHRIX PENTAETHER FROM ENANTIOMERICALLY ENRICHED S-GLYCIDOL

Permethyl ether 1 from Tolypothrix conglutinata was synthesized follow ing the retrosynthetic analysis of Scheme 1. According to it, we combi ned aldehyde 3 [prepared from S-glycidol (7); cf. Schemes 2, 3] and la ctone 4 (also prepared from S-glycidol (7); cf, the preceding communic ation(\2\) and Scheme 4) to the enantiopure and diastereopure trimetho xy lactone 2 (Scheme 5). The C=O group of this lactone was removed thr ough the Criegee rearrangement of a derived lactol peroxonosylate (Sch eme 6); thereby, the C-C=O bond of lactone 2 was replaced with complet e retention of configuration by one C-OH bond of the resulting syn-con figured diol 18. Protecting group manipulations (Schemes 6, 7) and oxi dation of the resulting alcohol 21 to aldehyde 31 (Scheme 10) initiate d the three final operations: Cz-homologation with Ph3P=CH-CH=O (--> e nal 32), tosyl hydrazone formation (--> 34), and reduction/concomitant C=C bond migration. They led to the target ether 1 as a 89:11 mixture with the CH=CH-richer ether 36.