The kinetics and equilibrium position of place exchange (alkylthiol-for-alkylthiol) reactions of gold nanoparticles are reported. These reactions were monitored via a gas chromatography analysis of structurally similar incoming and outgoing alkylthiols, as a function of time. The place exchange reactions described here proceed to an equilibrium position, where Keq approximately 1. The product-time data follow Langmuir diffusion kinetics.

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

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Employed as a common chiral starting material, (-1-quinic acid (7) was converted in a concise manner to both enantiomers of the P,y-unsaturated ketone 12. On the one hand, (+)-12 was obtained by stereospecific borohydride reduction of the conjugated ketone intermediate 9, transketalization, and oxidation of the derived homoallylic alcohol using the Dess-Martin periodinane reagent. Alternatively, dehydration of the tertiary alcohol 13 and oxidation of the free hydroxyl group in 14 furnished (-1-12 in good overall yield. Reaction of (+)-12 with dichlorocerium TMS acetylide was followed by Pd (0)-assisted construction of the acyclic enediyne 21. Cyclization of this intermediate on treatment with KHMDS proved efficient, providing the esperamicin intermediate (-)-22 in 60% isolated yield. In an identical fashion -)-12 was converted to the enantiomeric bicyclic enediyne (+)-22. Subsequent liberation of the diol system, and selective oxidation of the allylic alcohol in 25 gave ketone 26. Reaction of this intermediate with Ph2S-NH monohydrate gave aziridine 27 which was readily converted to its carbamate derivative 28 in preparation for aziridine ring opening. Calicheamicin-71' (1) and esperamicin-A1 (2) are amongst the most potent antitumoral agents known, displaying in vitro and in vivo activities at ng/mL levels (IC5,,'s) against a number of tumor systems (B16 melanoma, Moser human carcinoma, HCT-116 carcinoma, and normal and vincristine resistant This activity derives from the capacity of the aglycone component of these two structurally unique "enediyne" @ Abstract published in Advance ACS Abstracts, April 1, 1995. (1) (a) Lee, M. D.; Dunne, T. S.; Siegel, M. M.; Chang, C. C.; Morton, G. 0.; Borders, D. B. J . Am. Chem. Soc. 1987,109, 3464. (b) Lee, M. D.; Dunne, T. S.; Chang, C. C.; Ellestad, G. A.; Siegel, M. M.; Morton, G. 0.; McGahren, W. J.; Borders, D. B. J . Am. Chem. SOC. 1987,109, 3466. (c) Lee, M. D.; Ellestad, G. A.; Borders, D. B. Acc. Chem. Res. 1991,24, 235. (2) (a) Golik, J.; Clardy, J.; Dubay, G.; Groenewold, G.; Kawaguchi, H.; Konishi, M.; Krishnan, B.; Ohkuma, H.; Saitoh, K.; Doyle, T. W. J. Am. Chem. SOC. 1987, 109, 3461. (b) Golik, J.; Dubay, G.; Groenewold, G.; Kawaguchi, H.; Konishi, M.; Krishnan, B.; Ohkuma, H.; Saitoh, K.; Doyle, T. W. J . Am. Chem. SOC. 1987, 109, 3462. (3)(a) Maiese, W. M.; Lechevalier, M. P.; Lechevalier, H. A.; Korshalla, J.; Kuck, N.; Fantini, A.; Wildey, M. J.; Thomas, J.; Greenstein, M. J. Antibiot. 1989,42, 558. (b) Lee, M. D.; Manning, J. K.; Williams, D. R.; Kuck, N. A.; Testa, R. T.; Borders, D. B. J . Antibiot. 1989,42,1070. (c) Konishi, M.; Ohkuma, H.; Saitoh, K.-I.; Kawaguchi, H.; Golik, J.; Dubay, G.; Groenewold, G.; Krishnan, B.; Doyle, T. W. Hangeland, J. J.; Townsend, C. A. J . Am. Chem. SOC. lsgO,ll2,4554. (h) De Voss, J. J.; Townsend, C. A.; Ding, W.-D.; Morton, G. 0.; Ellestad, G. A.; Zein, N.; Tabor, A. B.; Schreiber, S. L. J . Am. Chem. SOC. 1990, 112, 9669. (i) Zein, N.; Poncin, M.; Nilakantan, R.; Ellestad, G. A. Science 1989, 244, 697. 6 ) Zein, N.; M...

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