56689-42-0Relevant articles and documents
Chemoenzymatic Total Synthesis and Structural Diversification of Tylactone-Based Macrolide Antibiotics through Late-Stage Polyketide Assembly, Tailoring, and C-H Functionalization
Lowell, Andrew N.,Demars, Matthew D.,Slocum, Samuel T.,Yu, Fengan,Anand, Krithika,Chemler, Joseph A.,Korakavi, Nisha,Priessnitz, Jennifer K.,Park, Sung Ryeol,Koch, Aaron A.,Schultz, Pamela J.,Sherman, David H.
, p. 7913 - 7920 (2017/06/20)
Polyketide synthases (PKSs) represent a powerful catalytic platform capable of effecting multiple carbon-carbon bond forming reactions and oxidation state adjustments. We explored the functionality of two terminal PKS modules that produce the 16-membered tylosin macrocycle, using them as biocatalysts in the chemoenzymatic synthesis of tylactone and its subsequent elaboration to complete the first total synthesis of the juvenimicin, M-4365, and rosamicin classes of macrolide antibiotics via late-stage diversification. Synthetic chemistry was employed to generate the tylactone hexaketide chain elongation intermediate that was accepted by the juvenimicin (Juv) ketosynthase of the penultimate JuvEIV PKS module. The hexaketide is processed through two complete modules (JuvEIV and JuvEV) in vitro, which catalyze elongation and functionalization of two ketide units followed by cyclization of the resulting octaketide into tylactone. After macrolactonization, a combination of in vivo glycosylation, selective in vitro cytochrome P450-mediated oxidation, and chemical oxidation was used to complete the scalable construction of a series of macrolide natural products in as few as 15 linear steps (21 total) with an overall yield of 4.6%.
Novel Semisynthetic Oxo and Alkyl Macrolide Antibacterials and Related Derivatives
Fishman, Andrew G.,Mallams, Alan K.,Puar, Mohindar S.,Rossman, Randall R.,Stephens, Richard L.
, p. 1189 - 1210 (2007/10/02)
An efficient method of protecting the 10,11-double bond in dienone and epoxy enone 16-membered macrolides has been developed.This involves Michael addition of thioacetic S-acid to the 10,11-ene to give exclusively the 11-acetylthio derivatives, which can be smoothly deprotected by treatment with fluoride ion.The protected intermediates have been used to prepare a novel class of macrolide antibacterials in which the aldehyde group has been converted into an alkyl ketone by reaction with the appropriate diazoalkane.Thus 20-oxo analogues of rosaramicin, 12,13-de-epoxy-12,13-dehydro-rosaramicin, tylosin, and desmycosin have been prepared.The reaction of diazomethane with unprotected macrolides has also been studied including the synthesis of 18-C-methyl-3''-O-propionyl-leucomycin A5.Derivatives in which the 20-formyl group has been replaced by metal and by halogeno groups, as well as derivatives having a 2,3-ene are described.A number of base-catalyzed rearrangement products including desmycosin 8β,20α-aldol and desmycosin 8α,20β-aldol are also described.
