摘要：

Eight new compounds (1-8) were isolated by anti-bioassay-guided fractionation of an extract of lanigerum. The structures of calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3), calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of calanolide A (1) and calanolide B (4) was established by a modified Mosher's method. Calanolides A (1) and B (4) were completely protective against replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM, respectively), but were inactive against . Some of the related compounds also showed evidence of anti-activity. Studies with purified bacterial recombinant revealed that the calanolides are specific RT inhibitors. Moreover, calanolide A was active not only against the -resistant G-9106 strain of but also against the pyridinone-resistant A17 strain. This was of particular interest since the A17 virus is highly resistant to previously known specific, non-RT inhibitors (e.g., TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently common pharmacologic class. The calanolides represent a substantial departure from the known class and therefore provide a novel new anti-chemotype for drug .

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