Unusual rearrangement of 3-hydrazino-rifamycins leading to the enlargement of the "natural" ansa bridge.

Sir: As part of our effort aimed at the synthesis of new rifamycin derivatives,1) the 3-hydrazino derivatives of rifamycin S (2) and SV (3) have been obtained by treating 3-bromorifamycin S (1a) with isopropylidene-methyl hydrazine and with isopropylidene-methyl hydrazine followed by hydrazine, respectively.2) We wish to describe here a novel rearrangement of the ansa bridge under acidic conditions affording the new "unnatural" ansamycin (4) characterized by the presence of a free amino group in position 2. Compound 4 is obtained directly from hydrazine 3 or by treatment of the isopropylidene hydrazone 2 with 3 % aq. HCl in DMF: 1H NMR (C6D6) CH3-33, 5-0.70 ppm (d, J= 7 Hz); CH3-31 and CH3-34, 0.85 (d, J=7 Hz); CH3-32, 1.02 (d, J=7 Hz); CH3-30, 1.58 (s); CH3-13, 1.62 (s); CH3-36, 1.80 (s); H-22 and H24, 1.61.8 (m); H-26, 1.90 (ddq, J=6, 6 and 7 Hz); CH3-14, 2.32 (s); H-20, 2.34 (m); CH3N, 2.94 (s); H-23, 2.9'3.0 (m); CH3-37, 3.04 (s); H-27, 3.29 (bdd, J=6 and 7 Hz); H-21, 3.60 (bd, J=7 Hz); OH-21 and OH-23, 3.64 (bm) and 3.74 (bm); H-28, 5.26 (dd, J=7 and 12 Hz); H-19, 5.28 (ddd, J-0.8, 7 and 16 Hz); H-25, 5.41 (dd, J=1 and 7 Hz); H-17, 5.82 (dd, J=0.8 and 10 Hz); H-29, 6.41 (bd, J=0.5 and 12 Hz); NH., 6.52 (bs); H-18, 6.79 (bdd, J=10 and 15 Hz); NHCO, 8.36 (bs); OH-8, 12.86 (s). Owing to the presence of the quinonimine tautomeric form1,3) of the amino-group of 4, the subsequent reactions of acylation and Schiff base formation to give 6 and 8, respectively, have been performed on the hydroquinone form.4) Namely, reduction (Zn/AcOH), treatment with acetyl chloride, and reoxidation to the quinone with MnO2 afford compound 6a (R. =CH3) from 4, whereas the reaction of the hydroquinone form of 4 with furfural yields 8. The formation of 4 is attributed to an intramolecular reaction of the 3-hydrazino-group