Benzoquinonoid ansamycins

Biochemical Studies Geldanamycin shows antitumor activity in vitro and in situ [1,3]. Uehara et al. found that geldanamycin and other benzoquinonoid ansamycins reversibly decrease the autophosphorylation of p60 and reverse the cell morphology from the transformed to the normal phenotype [4]. 

Uehara, Y., Hori, M., Takeuchi, T., Umezawa, H. (1986). Phenotypic change from transformed to normal induced by benzoquinonoid ansamycins accompanies inactivation of p60 in rat kidney cells infected with Rous sarcoma virus. Mol. Cell. Biol, 6, 2198-2206. 

A, the herbicidal benzoquinonoid ansamycin from 5.hvaroscooicus. has been... 

The flrst total synthesis of the benzoquinonoid ansamycin antibiotic herbimycin A has been reported.3 7 Methyl a-D-mannopyranoside played a key role in the synthesis of die C(9)-C(15) segment 56 (mannose numbering) which required legioselective reduction of the C(2)-branched epoxide 55 followed by homologation at C(6) (sugar numbering) (Scheme 13). 

Fig. 2. Structures of naturally occurring benzoquinonoid and benzenoid ansamycins...

The basic ansamycin structure consisting of a naphthoquinone or naphthohydroquinone ring and its spanning chain with its various substituents is required for antibacterial activity and E. coli RNA polymerase inhibition. Neither the rifamycin aromatic chromophore alone (18, Fig. 12) 126) nor streptovarone (Fig. 6) 104) has much activity, nor does the aliphatic ansa chain of rifamycin by itself (19, Fig. 12) or varicinal A (Fig. 6) 109). Cleavage of the ansa chain, as in the streptovals (Fig. 6) or rifarubin S (Fig. 20) (5), also leads to loss of activity. Benzoquinonoid and benzenoid ansamycins are not potent antibacterial agents. 

The electronic spectra of the ansamycins are complex, but most show high extinction coefficients (>25,000) at wave lengths below 230 nm, with maxima at longer wave lengths for the naphthoquinonoid antibiotics than for the benzoquinonoid compounds, as would be expected. Ultraviolet spectra of streptovaricin complex 84), rifamycins B 123), S 122) and SV (722), and geldanamycin (22) are shown in Fig. 28. That of maytansine 62) has not been published, but it is reported to have maxima at 223 (c 29,800), 243 (27,100 sh), 254 (27,200), 282 (5,690), and 290 nm (5,520). It is of some interest that the spectra of the streptovaricins resemble that of rifamycin S but not that of rifamycin B this hampered early recognition of the antibiotics similarity. 

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