Prado Soizic, Ledeit Hervé, Michel Sylvie, Koch Michel, Darbord Jacques Christian, Cole Stewart T, Tillequin François, Brodin Priscille
Laboratoire de Pharmacognosie, UMR/CNRS 8638, 4 avenue de l'Observatoire, 75006 Paris, France.
Bioorg Med Chem. 2006 Aug 1;14(15):5423-8. doi: 10.1016/j.bmc.2006.03.033. Epub 2006 Apr 17.
Alkylation of 2-hydroxydibenzofuran with 3-chloro-3-methyl-1-butyne, followed by Claisen rearrangement, gave access to 3,3-dimethyl-3Hbenzofuro[3,2-f][1]-benzopyran. Several derivatives modified at the pyran 1,2-double bond were prepared, including the corresponding dihydro compound and (+/-)-cis-diol, which was converted into diacetate and cyclic carbonate upon acylation. Both 3,3-dimethyl-3Hbenzofuro[3,2-f][1]benzopyran and 1,2-dihydro-3,3-dimethyl-3Hbenzofuro[3,2-f][1]benzopyran displayed significant activities when tested against Mycobacterium tuberculosis H37Rv and Beijing strains, with MIC99 in the range of 1-10 microg/ml. Further biological studies demonstrated good activities against drug-resistant mycobacterial strains. These compounds appear as promising specific antitubercular agents, since they exhibited neither significant cytotoxicity against mammal cells, nor effect on the growth of various bacteria and fungi.
2-羟基二苯并呋喃与3-氯-3-甲基-1-丁炔进行烷基化反应，随后进行克莱森重排，得到了3,3-二甲基-3H-苯并呋喃并[3,2-f][1]-苯并吡喃。制备了几种在吡喃1,2-双键处修饰的衍生物，包括相应的二氢化合物和(+/-)-顺式二醇，后者经酰化后转化为二乙酸酯和环状碳酸酯。3,3-二甲基-3H-苯并呋喃并[3,2-f][1]苯并吡喃和1,2-二氢-3,3-二甲基-3H-苯并呋喃并[3,2-f][1]苯并吡喃在针对结核分枝杆菌H37Rv和北京菌株进行测试时均表现出显著活性，MIC99在1-10微克/毫升范围内。进一步的生物学研究表明，它们对耐药分枝杆菌菌株具有良好的活性。这些化合物似乎是有前景的特异性抗结核药物，因为它们对哺乳动物细胞既没有显著的细胞毒性，对各种细菌和真菌的生长也没有影响。
