کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1388893 | 1500892 | 2012 | 6 صفحه PDF | دانلود رایگان |

The UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) is a promising target for the development of novel antibiotic substances against multidrug-resistant Gram-negative bacteria.The C-aryl glycoside 3 was designed as conformationally constrained analogue of the potent LpxC-inhibitor CHIR-090.The chiral pool synthesis of 3 started with d-mannose. The C-aryl glycoside 8 was synthesized stereoselectively by nucleophilic attack of 4-iodine-substituted phenyllithium and subsequent reduction with Et3SiH. The ester 10 was obtained in a one-pot diol cleavage, CrO3 oxidation, and esterification. A Sonogashira reaction of the aryl iodide 11 led to the alkyne 17 which was transformed with H2NOH into the hydroxamic acid 3.
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► We designed a conformationally constrained CHIR-090 analogue.
► A hydroxamic acid possessing a C-glycosidic scaffold was prepared in a convergent synthesis.
► A chiral pool synthesis was established giving access to a novel class of LpxC inhibitors.
Journal: Carbohydrate Research - Volume 359, 1 October 2012, Pages 59–64