An efficient synthesis of bis(indolyl)methanes and evaluation of their antimicrobial activities

Figures & data

Figure 1.  Chemical structures of bis(indole) alkaloids, I. , II isolated from Aspidosperma ramiflorum and III, IV from sponge Spongosorites sp., nifuroxazide (V) and nitrofuryl BIM (3q).

Table I.  Al(OTf)₃ catalysed synthesis of BIM derivatives (3a. –v) by the condensation of indole with various aldehydes.

Product	R	Time (min)	Yield (%)^a,b
3a	C6H5	14	95
3b	2-Cl–C6H4	4	92
3c	4-Cl–C6H4	6	90
3d	4-Br–C6H4	30	80
3e	2-NO2–C6H4	28	80
3f	3-NO2–C6H4	30	80
3g	4-NO2–C6H4	30	85
3h	4-Me–C6H4	20	95
3i	4-OMe–C6H4	12	92
3j	4-^iPr–C6H4	3	95
3k	3,4,5-tri-OMe–C6H2	25	80
3l	3,4-di-Cl–C6H3	30	85
3m	2-OH–C6H4	55	75
3n	4-OH–C6H4	45	80
3o	3-OMe-4-OH–C6H3	35	75
3p	2-Furyl	14	80
3q	5-Nitrofuryl	35	82
3r	2-Thienyl	25	80
3s	5-Nitrothienyl	60	80
3t	CH3	40	85
3u	C2H5	35	80
3v	C4H9	25	96

^a Yield obtained with 0.5 mol% Al(OTf)₃

^b Based on isolation by column chromatography and the products were characterized by NMR, IR and MS.

Table II.  Antibacterial activity^a of BIMs expressed in zone of inhibition in millimetres.

Compound	Gram-positive				Gram-negative
	B. Subtilis		S. aureus		E. coli		P. aeruginosa		P. oleovorians		K. pneumoniae
	100 μg/ml	150 μg/ml	100 μg/ml	150 μg/ml	100 μg/ml	150 μg/ml	100 μg/ml	150 μg/ml	100 μg/ml	150 μg/ml	100 μg/ml	150 μg/ml
3a	8	9	10	12	10	11	9	10	10	11	–	–
3 g	9	10	10	11	9	10	8	10	8	9	–	–
3i	9	10	–	9	11	12	–	9	9	10	–	–
3p	11	14	14	16	12	14	12	14	13	14	11	12
3q	16	17	11	13	14	17	12	14	17	18	12	14
3r	8	10	10	11	11	13	9	10	9	10	–	–
3s	10	12	11	12	11	14	10	11	12	13	10	10
3t	15	16	14	16	17	17	10	11	15	16	12	14
3u	16	18	14	17	15	18	15	19	16	18	11	15
3v	12	13	13	14	12	13	10	13	12	13	11	12
Strept	19		21		29		24		29		23

^aThe tests were performed in duplicate and repeated thrice; –, bacteria are resistant to the compound at the concentrations; Strept, Streptomycin (50 μg/ml).

Scheme 1.  Synthesis of BIMs.

Table III.  Antifungal activity of BIMs expressed in zone of inhibition in millimetres.

Compd	Yeast		Filamentous fungi
	C. albicans		R. oryzae		A. niger
	100 μg/ml	150 μg/ml	100 μg/ml	150 μg/ml	100 μg/ml	150 μg/ml
3a	10	12	–	–	–	–
3g	10	14	–	–	–	–
3i	–	–	–	–	–	–
3p	–	–	10	12	–	–
3q	8	9	8	9	10	11
3r	10	12	–	–	–	–
3s	9	10	8	9	9	11
3t	12	14	18	20	12	14
3u	10	13	13	15	14	18
3v	–	–	10	12	–	–
Amph	23		23		22

–, No activity has shown; Amph, Amphotericin B (50 μg/ml).