Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin^*

Figures & data

Figure 1. Alignment of conformers of CLA with the benzoxoboroles substituent at C-9 and 4″-O. Structure of CLA’s core was taken from 1J5A.pdb. Benzoxoborole tails were optimized in RNA’s environmental and the structure of RNA was omitted. Distances (in angstroms) are shown as dashed lines.

Scheme 1. Synthesis of clarithromycin derivatives 1–5.

Table 1. MIC’s (μg/mL) of the compounds against test-strains of Gr + and Gr − microbes^a.

Compound ID	S. aureus 25923	S. epidermidis 12228	S. pneumoniae 49619	E. feacalis 29212	E. coli 25922	K. pneumoniae 13883	S. cholerasuis 14028	P. aeruginosa 27853
2a	1.0	1.0	8.0	8.0	>64.0	>64.0	>64.0	>64.0
2b	2.0	0.5	4.0	8.0	>64.0	>64.0	>64.0	>64.0
5a	2.0	2.0	2.0	4.0	>64.0	>64.0	>64.0	>64.0
5b	2.0	0.5	0.5	4.0	>64.0	>64.0	>64.0	>64.0
CLA	1.0	1.0	4.0	4.0	>64.0	>64.0	>64.0	>64.0
BB A	>64.0	>64.0	>64.0	>64.0	16.0	16.0	16.0	16.0
BB B	>64.0	>64.0	>64.0	>64.0	1.0	1.0	1.0	1.0

^a Standard error of MIC was less than 0.1.

Table 2. MICs (mg/mL) E. coli K12 WT and tolC strains of E. coli^a.

Compound ID	WT	tolC	tolC pUC57 msr-E, mphE	tolC pUC erm42
2b	>64	8	>64	16
5a	>64	8	>64	16
5b	>64	16	>64	32
AN9246	32	1	>64	2
Erythromycin	>64	2	>64	8
Telithromycin	16	0,5	>64	0,5

^a Standard error of MIC was less than 0.1.