A Method for the Introduction of Reporter Groups into Moenomycin A, Based on Thiouronium Salt Chemistry

Abstract

p‐Alkoxy‐substituted cinnamylthiouronium salts 7, 13, 21a, and 21b reacted selectively with the 2‐acylamino‐1,3‐cyclopentanedione unit A of moenomycin A (1) to give the corresponding 2‐alkylated products 14a, 14b, 22a, and 22b. These products, depending on the pH of the solution, were either stable under the reaction conditions or they underwent retro‐Claisen‐type reactions. The method can be used for the attachment of reporter groups to moenomycin A for the synthesis of, for example, 25. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Moenomycin family antibiotics: chemical synthesis, biosynthesis, and biological activity

“…It assumed that the chromophore is not essential for the interaction between PGT and 1 , although it may provide additional contacts to the enzyme, making 1 a tighter binder. Compounds containing various fluorophores, tags or ampicillin instead of the A ring were shown to have, at best, 1-10% potency of 1 ( 33-39, 41, 43-45 ),83, 85, 86, 91 and some of them were virtually inactive ( 40 , 42 ) 86, 88, 89. As a general trend, compounds having less bulky substituents or those attached via long linker have higher potency.…”

“…Compounds containing various fluorophores, tags or ampicillin instead of the A ring were shown to have, at best, 1-10% the potency of 1 (33-39, 41, 43-45), 83,85,86,91 and some of them were virtually inactive (40,42). 86,88,89 As a general trend, compounds having less bulky substituents or those attached via a long linker have higher potency.…”

“…Other triazole derivatives include moenomycin dimers87 as well as analogs fused to an aminocoumarin moiety ( 42 ),88 various fluorescent labels (for example 43 , carrying fluorescein isothiocyanate)85 and ampicillin ( 44) 84. Another approach, based on thiouronium salt chemistry, also yielded a number of moenomycins with a modified unit A, exemplified by 45 89. Fundamental studies on cell wall biosynthesis were the main area of application of the A ring-modified moenomycins 88, 90-92.…”

“…84 Another approach, based on thiouronium salt chemistry, also yielded a number of moenomycins with a modified unit A, exemplified by 45. 89 Fundamental studies on cell wall biosynthesis were the main area of application of the A ring-modified moenomycins. 88,[90][91][92] Fluorescein-labeled moenomycin was used for the development of a fluorescence anisotropy-based highthroughput assay for PGT inhibitors.…”