122948-76-9Relevant academic research and scientific papers
Studies of the Immunosuppressive Agent FK-506: Synthesis of an Advanced Intermediate
Ragan, John A.,Nakatsuka, Masashi,Smith, David B.,Uehling, David E.,Schreiber, Stuart L.
, p. 4267 - 4268 (1989)
The addition of a vinyl anion that corresponds to C27 of the immunosuppressant FK-506 to an aldehyde that corresponds to C26 results in a coupling process that is stereoselective and convergent and allows for the direct attachment of the C26-pipecolinate
Total synthesis of FK506 and an FKBP probe reagent, (C8,C9-13C2)-FK506
Nakatsuka, Masashi,Ragan, John A.,Sammakia, Tarek,Smith, David B.,Uehling, David E.,Schreiber, Stuart L.
, p. 5583 - 5601 (2007/10/02)
Asymmetric syntheses of FK506 and (C8,C9-13C2)-FK506 are reported. The latter compound was designed to facilitate an investigation of the interactions between FK506 and its receptor, the recently discovered immunophilin, FKBP. The syntheses involved the preparation of intermediates 7-9 in nonracemic form; the key coupling reactions included a Cram-selective addition of the vinyl Grignard reagent derived from bromide 9 to aldehyde 8 and the addition of the lithioanion of phosphonamide 7 to aldehyde 51, followed by thermal elimination. Dithiane 65 was then hydrolyzed, and glycolic ester 6 (or 6*) was added via an aldol reaction that allowed the introduction of 13C labels at C8 and C9. Elaboration to FK506 proceeded via a Mukaiyama lactamization reaction and a selective deprotection/oxidation sequence, the efficiency of which was critically dependent upon the order of protecting group removal.
