LC-MS-Guided Isolation of Insulin-Secretion-Promoting Monoterpenoid Carbazole Alkaloids from <i>Murraya microphylla</i>

Fifteen new structurally unique monoterpenoid carbazole alkaloids, including two pairs of epimers (1/2 and 3/4), three pairs of enantiomers (6a/6b, 7a/7b, and 8a/8b), and five optically pure analogues (5, 9–12), were obtained from a 95% aqueous EtOH extract of Murraya microphylla by a combination of bioassay- and LC-MS-guided fractionation procedures. Their structures were established based on NMR and HRESIMS data interpretation. The absolute configuration of compound 1 was determined via X-ray crystallographic data analysis and for all compounds by comparison of experimental and calculated ECD data. Compounds 1–5 were assigned as five new thujane–carbazole alkaloids, and compounds 6–12 as 10 new menthene–carbazole alkaloids linked through an ether or carbon–carbon bond. Compounds 1–12 promoted insulin secretion in the HIT-T15 cell line, 1.9–3.1-fold higher than the gliclazide control at 100 μM.