A Formal Synthesis of FK-506. Exploration of Some Alternatives to Macrolactamization

Article abstract of DOI:10.1021/jo00296a042

The coupling of the previously described subunits 2, 3, and 4 is described.The C28-C27 E-double bond is fashioned from a sulfurane induced dehydration of alcohol 11.The C19-C20 E-double bond was constructed via a modified Julia process culminating in a reductive elimination of a vicinal trifluoroacetoxy sulfone (see 22 -> 23 -> 24 and 25).The synthesis of intermediates anticipating potential macrolactonization are also described.