406 R = COCH2NH2, X = NH2, Y = OH Compounds 405 and 406
3-hydroxyl group with DAST gave the 3-fluoro derivative, and oxidation of the free hydroxyl group followed by sodium borohydride reduction and the subsequent fluo-rination afforded the e^/-fluoro compound. Likewise, PCC oxidation of the hydroxyl group at position 3 followed by fluorination of the resulting oxo derivative furnished the difluoro analog. Of these analogs, the 3-fluoro derivative 408 showed less toxicity and more activity than sporaricin A .
Replacement of the 3-0-methyl group of sporaricin A with allyl group via hydroiodic acid assisted removal of the methyl group, followed by allylation of the free 3-hydroxyl group, led to preparation of the 3-O-substituted analogs 411-413 (compounds 407-413 ). These compounds were synthesized by epoxidation of the allylic double bond with mCPBA, followed by sequential treatment with sodium azide, water, or potassium cyanide. All these analogs exhibited high antibacterial activity against AAC(3)-I producing organisms. Among these analogs, compounds 411 and 413 showed enhanced activity against P. aeruginosa compared to the parent compound .
Total synthesis by a glycosylation method of the semisynthetic antibiotic 3-0-methylsporaricin A has been described . Other reports describe the preparation of a series of fluorinated sporaricin A, including 3-fluoro and 3,3-difluoro derivatives
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