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The conformer model of tryptophan photophysics ascribes the multiple fluorescence lifetimes to ground-state heterogeneity. It is usually assumed that the different conformers do not interconvert in the excited state. Previous studies of two constrained tryptophan derivatives supported this assumption (Colucci, W. J.; Tilstra, L.; Sattler, M. C.; Fronczek, F. R.; Barkley, M. D. J. Am. Chem. Soc. 1990, 112, 9182−9190; Yu, H.-T.; Vela, M. A.; Fronczek, F. R.; McLaughlin, M. L.; Barkley, M. D. J. Am. Chem. Soc. 1995, 117, 348−357). Five constrained derivatives have been synthesized and shown to undergo conformer inversion during the lifetime of the excited state. All derivatives have two ground-state conformations as determined by X-ray crystallography, molecular mechanics calculations, and 1H-NMR. Fluorescence lifetime data were fit to single- and double-exponential models and to a reversible two-state excited-state reaction model. 2-Amino-1,2-dihydrocyclopenta[b]indole-2-carboxylic acid has a single-exponential decay consistent with conformer inversion much faster than fluorescence decay. 1,2,3,4-Tetrahydrocarbazole-3-carboxylic acid, ethyl 1,2,3,4-tetrahydrocarbazole-3-carboxylate, and their 9-methyl derivatives have double-exponential decays with a minor second component of small positive or negative amplitude. Conformer inversion rates of ∼107 s-1 were determined by analyzing the fluorescence decay data using the excited-state reaction model. Temperature dependence of the fluorescence lifetimes was measured in H2O and D2O, and solvent quenching rates were calculated from the Arrhenius parameters. The carboxylate and carbonyl functional groups appear to have little effect on solvent quenching of indole fluorescence. Model calculations examining the effect of conformer inversion rate on the decay parameters of a biexponential model indicate that the presence of a small amplitude, short lifetime component may be a good predictor of excited-state conformer interconversion of tryptophans in peptides and proteins.

5223in context with the biosynthetic studies on the kinamyc i n~~~ and on metabolites of the toromycin/gilvocarcin group (e.g., chrysomycin B33) an angucyclinone-type intermediate was proven and assumed, respectively, which undergoes a rearrangement leading to the found structures. Thus, a strong similarity of the polyketide synthases of (32) Seaton, P. J.; Gould, S. J. J. Am. Chem. SOC. 1987, 109, (33) Carter, G. T.; Fantini, A. A.; James, J. C.; Borders, D. B.; White, 5282-5284. R. J. J. Antibiot. 1983, 38, 242-248. these antibiotic groups with the angucycline-PKS is or seems to be evident.Such similarities of the polyketides synthases may have implications in future biosynthetic studies on the different types of multicyclic polyketides which cannot be carried out without the tools of genetic engineering and/or mutagenesis. This also justifies further biosynthetic studies on the angucyclines, which will be focused on in early biosynthetic step, since these may be also relevant for the clinically important tetracyclines and anthracyclines.The C(1) triol group in the antibiotic, bicyclomycin (1) has been proposed to play an integral role in the bonding of key protein nucleophiles to the distal C (5)-C(5a) terminal double bond in the drug. Evidence in support of this concept has been provided by the comparison of the reactivities of bicyclomycin (l), the [N(d)-C(B')]-cyclized bicyclomycin adduct 3, 2',3'-bicyclomycin acetonide (17), and the acetonide derivative of 3, 18, with sodium ethanethiolate. Significantly, 3 displayed enhanced reactivity versus 1, 17, and 18 in this transformation. The controlling factors for the increased reactivity of 3 have been discerned and the importance of the C(1') hydroxyl group delineated. Key kinetic parameters are reported for the treatment of both 3 and 17 with 2-mercaptopyridine. Structural details are provided for both C(5a) thiolate and amine adducts of 3. The importance of these findings in relation to the mode of action of bicyclomycin are briefly discussed. (10) (a) Williams, R. M.; Tomizawa, K.; h t r o n g , R. W.; Dung, J.-S. The following uninverted Chemical Abstracts Index name for 3 modified by current IUPAC guidelines has been kindly provided by Dr. P. M. Giles (Chemical Abstract Services): (5R,SR,lOS,lOaS)-hexahydro-5,9,10-trihydroxy-9-methyl-4-methylene-8~-5,lOa-(iminomethano)-6H-pyrrolo [ 2,lb] [ 1,3] oxazocine-6,1 l-dione. 8-10,20,24, and 27 importance of the C(1) triol moiety in activating the distal exomethylene group in bicyclomycin at moderate "pH" values. RCHg k-u s 2 Q 9 248 2z RH --OMS 2 3 X-Y-OH U X,Y = OC(CH&O Scheme I. Potential Pathways for the Formation of Compounds Results and DiscussionOur studies began with the observation that treatment of the known bicyclomycin-3'-0-methanesulfonateg (4) with 2 equiv of the heterocyclic amines, morpholine (5), Nacetylpiperazine (6), and N-methylpiperazine (71, led to the efficient production of 8-10, respectively.12 Inspection of the 'H and '3c NMR spectra for these adducts indicated that functionaliza...

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SDP (Frenz, 1985), scattering factors of Cromer &