Strategies for ansamycin antibiotics. Asymmetric synthesis of the C(3)-C(21) subunit of herbimycin A

The asymmetric synthesis of 25, which constitutes the C(3)-C(21) segment of the stereochemically complex ansa chain of herbimycin A (2) has been achie ved. The approach features the furan-hydropyran transformations 7-->5 and 8 -->6 and the fragment coupling of 5 and 6 to produce the trisubstituted alk ene 4 with high stereoselectivity. Stereoselective addition of the aryl ani on derived from 24, which possesses the novel BIPSOP protecting group for t he primary amine function, to the lactol 22 then delivered 25 as the major product. (C) 1999 Elsevier Science Ltd. All rights reserved.