The principal investigator notes that the recently discovered class of remarkably effective anti-HIV natural products known as the calanolides are extremely difficult to obtain from natural sources. He reports that in his Phase I work, he has completed the total synthesis of racemic calanolide A, the most potent of the compounds reported, using readily available starting materials. He states that during the Phase II research program, he plans to improve his synthetic methodology so as to prepare large quantities of calanolide A in an efficient and economical manner, and that he also intends to design and synthesize a number of selected analogs of calanolide A which may possess more potent anti-HIV activity, fewer side effects, and better drug delivery properties than the parent natural product.
| Zembower, D E; Liao, S; Flavin, M T et al. (1997) Structural analogues of the calanolide anti-HIV agents. Modification of the trans-10,11-dimethyldihydropyran-12-ol ring (ring C). J Med Chem 40:1005-17 |
| Flavin, M T; Rizzo, J D; Khilevich, A et al. (1996) Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers. J Med Chem 39:1303-13 |
