401520-01-2Relevant academic research and scientific papers
Precursor directed biosynthesis of an orthogonally functional erythromycin analogue: Selectivity in the ribosome macrolide binding pocket
Harvey, Colin J. B.,Puglisi, Joseph D.,Pande, Vijay S.,Cane, David E.,Khosla, Chaitan
, p. 12259 - 12265 (2012)
The macrolide antibiotic erythromycin A and its semisynthetic analogues have been among the most useful antibacterial agents for the treatment of infectious diseases. Using a recently developed chemical genetic strategy for precursor-directed biosynthesis and colony bioassay of 6-deoxyerythromycin D analogues, we identified a new class of alkynyl- and alkenyl-substituted macrolides with activities comparable to that of the natural product. Further analysis revealed a marked and unexpected dependence of antibiotic activity on the size and degree of unsaturation of the precursor. Based on these leads, we also report the precursor-directed biosynthesis of 15-propargyl erythromycin A, a novel antibiotic that not only is as potent as erythromycin A with respect to its ability to inhibit bacterial growth and cell-free ribosomal protein biosynthesis but also harbors an orthogonal functional group that is capable of facile chemical modification.
Synthesis of natural fragrant molecules cis-3-methyl-4-decanolide and aerangis lactone. General enantioselective routes to beta,gamma-cis-disubstituted gamma-lactones and gamma,delta-cis-disubstituted delta-lactones.
Wu, Yikang,Shen, Xin,Tang, Chao-Jun,Chen, Zhi-Long,Hu,Shi, Wei
, p. 3802 - 3810 (2007/10/03)
General enantioselective routes to 3,4-cis-dialkyl substituted gamma-lactones and 4,5-cis-dialkyl substituted delta-lactones using TiCl(4)-mediated Evans asymmetric aldolization as the key step are reported. The syntheses are exemplified with two natural fragrant molecules, cis-3-methyl-4-decanolide (1) and aerangis lactone (2). The (R,R) steroegenic centers were established using (S)-phenylalanine-derived 2-oxazolidinone or thiazolidinethione as chiral auxiliary, whereas the (S,S) ones were constructed with auxiliary prepared from (R)-phenylglycine. NaBH(4)/CaCl(2)/THF in the presence of a small amount of EtOH was introduced as a new effective method for reductive cleavage of chiral oxazolidinone auxiliaries. Previously unknown, tricky concentration effects were observed during the monotosylation of diol 7 and BOM protection of Evans aldol 23.
An expeditious access to enantiomerically pure cis-dialkyl-substituted γ- and δ-lactones
Wu,Shen,Tang,Chen
, p. 3428 - 3432 (2007/10/03)
A facile general route to enantiomerically pure 3,4-cis-dialkyl-substituted γ-lactones and 4,5-cis-dialkyl-substituted δ-lactones by TiCl4-mediated Evans asymmetric aldolization as the key step is exemplified by synthesis of cis-(3R,4R)-3-methy
