Subject(s)
Toxicology , Toxicology , Biodiversity , Poisons , Poisoning , Toxins, Biological , Toxicology , Allergy and Immunology , Zoology , BiodiversityABSTRACT
An efficient and stereoselective synthesis of the C13-C23 part (8) was achieved starting from methyl (R)- and (S)-3-hydroxy-2-methylpropionates (9) via coupling of the C13-C17 aldehyde (6), prepared by Evans asymmetric aldol reaction, with the C18-C21 iodoalkene (5b) by taking advantage of the 3,4-dimethoxybenzyl protecting group.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Antibiotics, Antineoplastic/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antibiotics, Antineoplastic/pharmacology , Lactones/chemical synthesis , Lactones/pharmacology , Macrolides , Oxidation-Reduction , Spectrometry, Mass, Fast Atom Bombardment , StereoisomerismABSTRACT
The synthesis of acetomycin and related analogs was investigated. Acetomycin was synthesized from diethyl allyl(methyl)malonate in 6.5% yield over 18 steps. The total number of steps was improved compared to our previous synthesis; i.e., four steps shorter, and the total yield was 4.5% greater than the previous synthesis. Acetomycin analogs with benzoyloxy and pivaloyloxy groups, instead of an acetoxy group at the 5-position of the gamma-butyrolactone ring were designed as esterase-resistant models and prepared similarly. Although they showed a similar level of cytotoxicity as acetomycin in vitro, they were not resistant to porcine liver esterase, and lost cytotoxicity in vivo.
Subject(s)
Antibiotics, Antineoplastic/chemical synthesis , Antibiotics, Antineoplastic/metabolism , Esterases/metabolism , Animals , Antibiotics, Antineoplastic/pharmacology , Drug Stability , Furans/chemical synthesis , Furans/metabolism , Furans/pharmacology , Growth Inhibitors/chemical synthesis , Growth Inhibitors/metabolism , Growth Inhibitors/pharmacology , Humans , Inhibitory Concentration 50 , KB Cells , Leukemia L1210 , Mice , Stereoisomerism , Structure-Activity Relationship , SwineABSTRACT
The C1-C12 part (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methylpropionate (11a) via a coupling between the C1-C7 aldehyde (6) and the C8-C11 iodoalkene (7a). For a synthesis of 6, a mismatched but highly efficient Sharpless dihydroxylation of the alpha, beta-unsaturated ester (15) with AD-mix-alpha was successfully applied. Compound 7a was synthesized using hydrozirconation to the alkyne (32).
Subject(s)
Anti-Bacterial Agents/chemistry , Antibiotics, Antineoplastic/chemistry , Cyclization , Hydroxylation , Lactones/chemistry , Macrolides , Models, Molecular , Molecular Conformation , StereoisomerismABSTRACT
1'-Deoxy-4'-thioribonucleoside 1 was synthesized from acyclic allylic alcohol 2 by 8 steps. TMSOTf and SnCl4 were found to be a good mediator for the key coupling of thiafuranose part with pyrimidine base to give beta-isomer preferentially.
