Streptovaricin triacetate

The relationships among the various streptovaricins were shown by the following reactions streptovaricin E (8) converts to streptovaricin C (6) upon treatment with sodium borohydride streptovaricins A (4), G (9), and K (11) yield the same triacetate derivative upon acetylation streptovaricins B (5), C (6), and J (10) yield the same tri- and tetraacetate derivatives upon acetylation streptovaricin G (9) converts to streptovaricin (12) upon treatment with base (4). The open-chain streptovaricin U (13) has also been isolated from the streptovaricin complex (5). 

C53H6iBBrCl2NOi7, Streptovaricin C triacetate (cyclic p-bromobenz-eneboronate atropisomer) - methylene dichloride (1 1), 42B, 393 C54H9ol4KNgOi8r Valinomycin potassium iodide, 41B, 1240 C54H9oNgOi8r Valinomycin, 41B, 588... 

Fig. 4. Three-dimensional stereo models of ansamycins and their derivatives A) atropiso-streptovaricin C triacetate cyclic p-bromobenzeneboronate (1), B) rifamycin B p-iodo-anilide (2), C) rifamycin Y p-iodoanilide (3), D) tolypomycinone tri-m-bromobenzoate (5), E) maytansine 3-bromopropyl ether (6), F) geldanamycin. All drawings except that for geldanamycin are from Wang and Paul 148) that for geldanamycin was obtained from Dr. D. J. Duchamp, The Upjohn Company (25)...

Derivatives of streptovaricins also can be converted to their atropisomers, sometimes at lower temperatures than the streptovaricins themselves. In refluxing benzene an equilibrium mixture of streptovaricin C triacetate and its atropisomer is formed. This reaction led to a complication in assigning the structure of streptovaricin C by x-ray crystallography (149), since the x-ray study was carried out on a cyclic / -bromobenzene-boronate formed by heating streptovaricin C triacetate in benzene with /7-bromobenzeneboronic acid and the atropisomeric cyclic /7-bromo-... 

The most extensively studied streptovaricin derivatives are the streptovaricin acetates 103). As noted in Section II.A., acetylation was a key reaction in interrelating the structures of the streptovaricins. Since streptovaricins A, G and K all give the same compound, streptovaricin G triacetate (streptovaricins A and K diacetate), on acetylation, and streptovaricins A and K have one more acetate group than streptovaricin G, streptovaricins A and K are monoacetates of streptovaricin G. Similarly, streptovaricins C, B and J give the same compounds, streptovaricin C tri- and tetraacetates (streptovaricins B and J di- and triacetates), and streptovaricins B and J have one more acetate group than streptovaricin C. The positions of the acetates in streptovaricins A, B, J and K were located by shifts of appropriate protons in magnetic resonance spectra. 

Although multi-acetylation reduced antibacterial activity, when streptovaricin C tri- and tetraacetates and streptovaricin G triacetate were tested against the reverse transcriptase of Rauscher leukemia virus (RLV), the acetylated compounds proved to be more active than the unacetylated or mono-acetylated streptovaricins. The atropisomers of the streptovaricin oligoacetates are also inactive as antibacterial agents or inhibitors of E. coli RNA polymerase but more active in inhibiting reverse transcriptase. The cyclic benzeneboronate and p-bromobenzeneboronate derivatives of streptovaricin C (11, 13, respectively) and atropisostrepto-varicin C (12, 1, respectively) triacetates, shown in Fig. 11, also inhibit reverse transcriptase but are inactive as antibacterial agents. 

Wang, A. H.-J., and I. C. Paul Structure of a Derivative of Streptovaricin C Triacetate Crystal and Molecular Structure of the Atropisomer of the Cyclic /7-Bromo-benzeneboronate Ester of Streptovaricin C Triacetate. To be submitted for publication. 

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