Total Syntheses of (±)-Spiroquinazoline, (—)-Alantryphenone, (+)-Lapatin A, and (-)-Quinadoline B

摘要

Since (-)-spiroquinazoline (1; Figure 1) was isolated by Barrow and Sun in 1994, eight other spiroquinazoline alkaloids have been isolated from a variety of fungi of the genera Penicillium and Aspergillus These natural products all contain a tricyclic pyrazino quinazolinedione moiety, but differ in the substructures which bridge C2 and C11. (—)-Spiroquinazoline (1), (—)-alantryphenone (2), alantryleu-none (3), alanditrypinone (4), (+)-lapatin A (5), and (—)-quinadoline B (9) are bridged by indoline-containing substructures with different C15 substituents, while lapatin B (6), alantrypinone (7), and serantrypinone (8) are bridged by a 3-methyleneoxindole unit. Preliminary studies have revealed that these alkaloids possessed significant biological activities. For example, 1 inhibits substance P (SP) binding to human NK-1 receptor and therefore may serve as a lead compound for developing analgesics. Alantrypinone (7) potently inhibits insect GABA receptors but is much less active toward mammalian GABA recep- tors. Additionally, 9 was found to inhibit lipid droplet synthesis in mouse macrophages.