Biotransformation of Patchouli Alcohol by Cladosporium cladosporioides and the Anti-Influenza Virus Activities of Biotransformation Products

The biotransformation of patchouli alcohol by Cladosporium cladosporioides afforded 31 products, including 21 new ones (1-3, 5, 6, 8-14, and 17-25). Their structures were determined by extensive spectroscopic data analysis (H-1 and C-13 NMR, HSQC, HMBC, H-1-H-1 COSY, ROESY, and HRESIMS), and the absolute configuration of compounds 1, 2, 8, 9, and 17 was determined by single-crystal X-ray diffraction using Cu K alpha radiation. Structurally, compounds 21-24 were patchoulol-type norsesquiterpenoids without Me-12. Among them, a Delta(3(4)) double bond existed in compounds 21 and 22; a three-membered ring was formed between C-4, C-5, and C-6 in compound 23; an epoxy moiety appeared between C-3 and C-4 in compound 24. Furthermore, the biotransformation products 9, 10, 12, and 25 showed potent anti-influenza virus activity with EC50 values of 2.11, 7.94, 20.87, and 3.45 mu M, respectively.