- A Practical, Component-Based Synthetic Route to Methylthiolincosamine Permitting Facile Northern-Half Diversification of Lincosamide Antibiotics
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The development of a flexible, component-based synthetic route to the amino sugar fragment of the lincosamide antibiotics is described. This route hinges on the application and extension of nitroaldol chemistry to forge strategic bonds within complex amino sugar targets and employs a glycal epoxide as a versatile glycosyl donor for the installation of anomeric groups. Through building-block exchange and late-stage functionalization, this route affords access to a host of rationally designed lincosamides otherwise inaccessible by semisynthesis and underpins a platform for the discovery of new lincosamide antibiotics.
- Mitcheltree, Matthew J.,Stevenson, Jack W.,Pisipati, Amarnath,Myers, Andrew G.
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supporting information
p. 6829 - 6835
(2021/05/29)
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- Practical Gram-Scale Synthesis of Iboxamycin, a Potent Antibiotic Candidate
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A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation-oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp3-sp2 Negishi coupling, and a one-pot transacetalization-reduction reaction to form the target compound's oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its in vivo profiling in murine models of infection.
- Mason, Jeremy D.,Myers, Andrew G.,Pote, Aditya R.,Terwilliger, Daniel W.
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supporting information
p. 11019 - 11025
(2021/08/03)
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- Allosteric modulators of 5-hydroxytryptamine 2C receptor (5-HT2CR)
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The disclosure is directed to compounds identified as allosteric modulators of 5-HT 2CR, as well as pharmaceutical compositions and methods using the same. Certain embodiments also include methods of identifying and methods of synthesizing the compounds. Optimization and development of allosteric 5-HT 2CR modulators that bind sites other than the primary ligand binding site generate novel, highly selective, and potent ligands of 5-HT2CR. Such molecules can be used as small molecule probes for the nervous system and as effective therapeutics for a variety of diseases.
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Page/Page column 42-43
(2017/01/26)
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- Synthesis of 1,2,3-triazole analogues of lincomycin
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In search for new antibiotics we replaced the amide moiety of lincomycin 1 by a 1,2,3-triazole ring. The 1,2,3-triazoles 10a-10k were obtained as single regioisomers by 'click reaction' of azide 5 with the alkyne 9k, derived from propyl hygric acid, and the alkyl, aryl, or cycloalkyl alkynes ribosomes 9a-9j. The new analogues proved inactive towards wild-type and A2058G mutant.
- Collin, Marie-Pierre,Hobbie, Sven N.,Boettger, Erik C.,Vasella, Andrea
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scheme or table
p. 1838 - 1848
(2009/02/07)
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- LINCOMYCIN DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY
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Novel lincomycin derivatives are disclosed. These lincomycin derivatives exhibit antibacterial activity. As the compounds of the subject invention exhibit potent activities against bacteria, including gram positive organisms, they are useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
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- Stereocontrolled lincomycin synthesis
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The synthesis from methyl α-D-galactopyranoside (6) of methyl thiolincosaminide (2), the direct synthetic precursor to lincomycin (1), is presented. The key step for controlling the off-pyranose stereocenters C-6 and C-7 is a novel intramolecular nitrogen delivery reaction using epoxy alcohol 10. Reaction of 10 with dimethylcyanamide in the presence of sodium hydride and imidazole leads to the oxazoline 14, a protected vicinal amino alcohol. The synthesis is completed by efficient exchange of acetal for thioacetal, followed by hydrolysis of the oxazoline and removal of the benzyl groups. The target 2 is obtained in 22 steps and 28% overall yield from 6.
- Knapp,Kukkola
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p. 1632 - 1636
(2007/10/02)
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