118977-92-7Relevant academic research and scientific papers
Efficient Degradation of FK-506 to a Versatile Synthetic Intermediate
Askin, D.,Joe, Daisy,Reamer, R. A.,Volante, R. P.,Shinkai, I.
, p. 5451 - 5454 (2007/10/02)
An 11-step degradation of natural FK-506 (1) to selectively protected C10-C34 synthetic intermediate 2 has been accomplished in 14percent overall yield.The key steps include; (a) lead tetracetate mediated C9-C10 bond cleavage of 24,32-bis(triisopropylsilyl)-FK-506 (3), (b) simultaneous C10 ester, C22 ketone reduction/C26 oxygen deacylation, and (c) selective bis(triethylsilylation) of the resulting triols 7a,b.The degradate 2 is ready for reacylation at the C26 hydroxyl terminus; hydrolysis of the dimethyl acetal moiety then provides an aldehyde ready for homologation at the C10 terminus.
Chemistry of tricarbonyl hemiketals and application of Evans' technology to the total synthesis of the immunosuppressant (-)-FK-506
Jones,Reamer,Desmond,Mills
, p. 2998 - 3017 (2007/10/02)
Details of model studies probing the chemistry of the tricarbonyl region of FK-506 are presented, and their use in designing a successful route to this immunosuppressant is outlined. Application of asymmetric oxazolidinone alkylation/aldol methodology to a convergent, highly flexible synthesis of the C10-C18 fragment and to improvements in the preparation of the C20-C34 segment are also discussed.
A Formal Synthesis of FK-506. Exploration of Some Alternatives to Macrolactamization
Jones, A. Brian,Villalobos, Annabella,Linde, Robert G.,Danishefsky, Samuel J.
, p. 2786 - 2797 (2007/10/02)
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.
