Erythronolide system

Few applications of cyclizations to form fused ring 8-lactones or tetrahydropyrans are found. Two consecutive bromolactonizations were used to effect stereoselective dihydroxylation of a cyclohexadi-enone system in a total synthesis of erythronolide B (Scheme S).64 Iodolactonization of an NJV-di-ethylbenzamide derivative to form a ds-fused benzolactone was a key step in a recent synthesis of pancratistatin.641 A di-fused tetrahydropyran was produced in good yield by intramolecular oxymercura-tion as shown in equation (17),59 although attempts to cyclize a more highly functionalized system have been reported to fail.65 Formation of a fused ring tetrahydropyran via an anti-Markovnikov 6-endo sel-enoetherification has been reported in cases where steric and stereoelectronic factors disfavor a 5-exo cyclization to a spirocyclic structure.38... 

RB Woodward, E Logusch, KP Nambiar, K Sakan, D Ward, B-W Au-Yeung, P Balaram, LJ Browne, PJ Card, CH Chen, RB Chenevert, A Fliri, K Frobel, H-J Gais, DG Garrat, K Hayakawa, W Heggie, DP Hesson, D Hoppe, I Hoppe. Asymmetric total synthesis of erythromycin. 2. Synthesis of an erythronolide A lactone system. J Am Chem Soc 103 3213-3215, 1981. 

Because of the intricacies associated with construction of the erythronolide framework, this group of macrolides served as the yardstick for accomplishment in this area, and as such has attracted considerable.attention. Consequently, we would like to develop, for the benefit of the reader, several other synthetic approaches that have been described (some of which are still under investigation). Although not total syntheses in the strictest sense, all of the efforts presented here have made substantial progress toward the elaboration of the stereochemistry of this complex system. We have by necessity exercised editorial judgment as to which among a number of ongoing efforts have been included in this chapter. Additionally, several other unpublished routes have recently been reviewed. ... 

Another concise approach to the erythronolide ring system was developed by Chamberlin and co-workers, as described in Scheme 2.20. Like Woodward... 

Woodward, R. B. etal "AsymmetricTotal Synthesis of Erythromycin. 2. Synthesis of an Erythronolide A Lactone System" J. Am. Chem. Soc. 1981, 103, 3213... 

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