Four pairs of proline-containing cyclic dipeptides from <i>Nocardiopsis</i> sp. HT88, an endophytic bacterium of <i>Mallotus nudiflorus</i> L

Abstract

Strain HT88 was isolated from the fresh stems of <i>Mallotus nudiflorus L</i>, and it was identified as <i>Nocardiopsis</i> sp. by analyzing its morphology and the 16S rRNA sequence. The extracts of fermented HT88 showed potent antimicrobial activities. Bioassay guided separation of extracts led to eight proline <i>(or hydroxyproline, Hyp)</i>-containing cyclic dipeptides. Their structures were determined by 1D and 2D NMR spectroscopy and ESI mass spectrometry and further comparison with existing ¹H and ¹³C NMR, melting points and specific rotation data. The eight 2,5-diketopiperazines (DKPs) were identified as cyclo(<i>L</i>-Pro<i>-L</i>-Leu) (<b>1</b>), cyclo(Pro-Leu) (<b>2</b>), cyclo(<i>L</i>-<i>trans</i>-Hyp-<i>L</i>-Leu) (<b>3</b>), cyclo(<i>D</i>-<i>trans</i>-Hyp-<i>D</i>-Leu) (<b>4</b>), and cyclo(<i>D</i>-Pro-<i>L</i>-Phe) (<b>5</b>), cyclo(<i>L</i>-Pro-<i>L</i>-Phe) (<b>6)</b>, and cyclo(<i>D</i>-<i>cis</i>-Hyp-<i>L</i>-Phe) (<b>7</b>), cyclo<i>(L-trans-</i>Hyp-<i>L-</i>Phe) (<b>8</b>), respectively. Up to date, this is the first isolation of four pairs of proline based DKPs from <i>Nocardiopsis</i> sp.