LC-MS-Guided Isolation of Insulin-Secretion-Promoting Monoterpenoid Carbazole Alkaloids from Murraya microphylla

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.