Subscribe to RSS
DOI: 10.1055/a-2467-4819
Multigram-Scale Macrobicyclic Thiolincosamine Synthesis
Practical Synthesis of Macrobicyclic Thiolincosamines.
J. Am. Chem. Soc. 2024;
146: 29135-29139
DOI: 10.1021/jacs.4c11270
Significance
The authors report highly scalable routes towards the northern portions (1 and 2) of two new broad-spectrum antibiotics: BT-33 and cresomycin. Dynamic kinetic resolution of an allenylzinc coupling partner permitted the diastereoselective propargylation of Ellman-type sulfinimine 4 with 1.2 equiv of the propargyl bromide pronucleophile 3 or 5. Subsequent cyclization sequences yielded the hydrochloride salts of 1 and 2 in multigram quantities to meet the material needs of preclinical drug development studies.
#
Comment
The reported protocol for the Barbier-type propargylation is a significant improvement upon existing methodology, permitting a near 1:1 equivalency of coupling partners with a racemic propargyl bromide and enantiomerically enriched sulfinimine. This impressive atom economy should enhance the utility of this transformation in complex molecule synthesis.
#
#
Publication History
Article published online:
20 December 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany