Synthesis And Antimicrobial Activity Of Indolyl Diketopiperazines

Indolyl diketopiperazines are a very important class of heterocycles and widely found in the nature. Due to their broad range of bioactivities, especially antimicrobial activities and anti-tumor activities, their synthesis has attracted much attention. In this paper, the synthetic methods and their development be reviewed, then the synthesis and antimicrobial activities of indolyl diketopiperazines be introduced.Eight kinds of N-substituted L-tryptophan methyl ester including 6a～6h was synthesized by four-step reactions starting from L-tryptophan, the first step, L-tryptophan methyl ester hydrochloride be synthesized through the "sulfuryl dichloride methods", then removed hydrochloride, reacted with eight kinds of aldehydes and ketones(benzaldehyde, anisaldehyde, cinnamaldehyde, furalde- hyde, salicylaldehyde, vanillic aldehyde, paradimethylaminobenzaldehyde, acetone)to give the Schiff base, the final step is selective reduction. Five compands (6b, 6d, 6e, 6f, 6g) among which are new compands have not been reported. The target compands is synthesized from Fmoc-L-proline by acyl chloride reaction and substituted reaction with N-substituted L-tryptophan methyl ester, then removed Fmoc- protecting group and ring closure in morphine.Five kinds of indolyl diketopiperazines was synthesizd through this route, three compands (1b, 1d, 1e) among which are new compands have not been reported. Total of 15 compounds including L-tryptophan methyl ester hydrochloride, eight kinds of N-substituted L-tryptophan methyl ester, five target compands and one by-product be produced in the course of this research were characterized by NMR, IR and elemental analysis.Two kinds of bacterias (Staphylococcus aureus, Esherichia coli) and five fungi (Alternaria brassicae, F. Graminearum, C. gloeosporioides, P. capsic, V. mali) be slected to test the antimicrobial activities of target compands. The results of activity test indicated that the five indolyl diketopiperazines all have the antimicrobial activities for these test microorganism with different degree, compand 1a had obvious antimicrobial activities on Staphylococcus aureus, the minimum inhibiting concentration was 1.56μg/ml, which closed to the sodium penicillin, besides, compand 1c had better antimicrobial activities on F. Graminearum, C. gloeosporioides and V. mali, the minimum inhibiting concentration was 6.25μg/ml, which has the same inhibition effect with ketoconazole as a positive contrast drug. The antitumor activity and other bioactivity of this five target compands needs to be futher study.